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Transcript of Paediatrics & child_health-_april_2008_(_neonatology)
Paediatrics and Child HealthPaediatrics and Child Health is the continuously updated review of paediatrics and child health (formerly Current Paediatrics)
Paediatrics and Child Health is an authoritative and comprehensive resource that provides all paediatricians and child health care specialists with up-to-date reviews on all aspects of hospitalcommunity paediatrics and neonatology including investigations and technical procedures in a 4-year cycle of 48 issues The emphasis of the journal is on the clear concise presentation of information of direct clinical relevance to both hospital and community-based paediatricians Contributors are chosen for their recognized knowl-edge of the subject The journal is abstracted and indexed in Current Awareness in Biological Sciences The layout of the journal including the design and colour enables fast assimilation of key information For ease of reference Paediatrics and Child Health is available in print and online formats
Editor-in-ChiefPatrick Cartlidge DM FRCP FRCPCH
Senior Lecturer in Child Health and Honorary Consultant Neonatologist Wales College of Medicine Cardiff University Cardiff UK
Visit our website at wwwpaediatricsandchildhealthjournalcouk for previous issues subscription information and further details
Paediatrics and Child Health has an eminent editorial board and a wide array of authors all of whom are recognized experts in their field
International Advisory BoardR Adelman (Phoenix USA) A Bagga (New Delhi India)
Z Bhutta (Karachi Pakistan) H Buller (Rotterdam The Netherlands)
MC Chiu (Kowloon Hong Kong) M Hassan (Islamabad Pakistan)
P Malleson (Vancouver Canada) A Martini (Genova Italy)
A Moosa (Saffat Kuwait) C Morley (Carlton Australia)
BJC Perera (Colombo Sri Lanka) J Pettifor (Johannesburg South Africa)
M Uchiyama (Niigata Japan) M van de Bor (Nijmegen The Netherlands)
Associate EditorsAllan Colver MA MD FRCPCH
Professor of Community Child Health Sir James Spence Institute Newcastle University Newcastle UK
Harish Vyas DM FRCP FRCPCH Professor in PICU and Respiratory Medicine Queenrsquos Medical Centre Nottingham University Hospital UK
Nicholas Mann MD FRCP FRCPCH DCH Consultant Paediatrician Department of Paediatrics Royal Berkshire Hospital Reading UK
Richard Wilson MB FRCP FRCPCH DCH Honorary Consultant Paediatrician Kingston Hospital Kingston-upon-Thames Surrey UK
Alistair Thomson MA MD BChir FRCPCH FRCP DCH DRCOG Consultant Paediatrician Leighton Hospital Crewe UK
Colin Powell MBChB DCH MRCP FRACP FRCPCH MD
Consultant Paediatrician University Hospital of Wales Cardiff UK
SympoSium neonatology
Temperature control in the neonateandrew lyon
Abstractthe control of body temperature is a challenge to the newborn baby
particularly if immature or sick Behavioural responses to environmental
temperature changes are almost non-existent the preterm baby has lim-
ited ability to mobilize energy sources to combat high heat losses par-
ticularly from evaporation there is evidence that many preterm babies
are still being allowed to get cold during stabilization and resuscitation
a low temperature at the time of admission to a neonatal unit is inde-
pendently associated with an increased mortality in the preterm infant
preventing evaporative heat losses at this time can abolish hypothermia
on admission Further studies are needed to determine the optimum
thermal management immediately after delivery there are no studies
that show any difference in outcome for preterm babies nursed in incu-
bators compared to those under radiant heaters High transepidermal
water loss (teWl) results in increased fluid and heat loss in the preterm
baby this can be managed by increasing environmental humidity al-
though this may be more difficult when babies are nursed under radiant
heaters nursing the baby in high humidity reduces teWl but more work
is needed to show if a reduction in water movement has an adverse ef-
fect on the rate of maturation of the skin the way a baby interacts with
their environment is always changing and whatever temperature and
humidity settings are first used it is necessary to monitor continuously
the thermal balance the continuous measurement and display of a cen-
tral and a peripheral temperature gives an early indication of cold stress
before there is any fall in the babyrsquos core temperature
Keywords centralndashperipheral temperature difference humidity
newborn preterm temperature control transepidermal water loss
Introduction
Children and adults maintain a constant deep body tempera-ture over a wide range of ambient thermal conditions (homeo-thermic) This is achieved by physiological and behavioural responses that control the rate at which heat is produced or lost The newborn infant is also homeothermic but control of body temperature can only be achieved over a narrower range of ambient conditions The preterm infant has even greater dif-ficulty in body temperature control and the most immature infants behave at times as if they are poikilothermic ndash their body
Andrew Lyon MA MB FRCP FRCPCH is Consultant Neonatologist at the
Simpson Centre for Reproductive Health Royal Infirmary of Edinburgh
Little France Edinburgh EH16 4SA UK
paeDiatRiCS anD CHilD HealtH 184 15
temperature tending to drift up and down with the ambient tem-perature The aim in neonatal care is to provide a thermal envi-ronment which keeps body temperature in the normal range and which does not stress the infant to produce or lose large amounts of heat
The importance of keeping newborn babies warm has been known for centuries1 In the 1950s William Silverman and others showed a clear link between temperature control and neonatal mortality In a series of randomized controlled trials they showed that keeping babies warm in incubators resulted in an absolute reduction in mortality of 2523 In many of these studies a sig-nificant numbers of babies were under 1000 g birthweight and the improvement in survival was seen in all birthweight groups No other single change in practice has had such a dramatic effect on mortality of the newborn baby
The EPICure study of a cohort of babies under 26 weeksrsquo ges-tation delivered in the UK in 1995 showed that low admission temperature was an independent risk factor for neonatal death even after adjustment for other known risks4 In this population study 30 43 and 58 of babies at gestations 25 24 and 23 weeks respectively who were admitted to neonatal units had an admission temperature below 35 degC The report of the CESDI 2728 project showed that in babies born at 27 and 28 weeksrsquo gestation an admission temperature below 36 degC was found in 73 of those who died compared with 59 in those who survived5
The importance of early temperature as a predictor of out-come in preterm babies is shown by its inclusion in risk scoring systems such as the Clinical Risk Index for Babies (CRIB)6 and the Score for Neonatal Acute Physiology ndash perinatal extension (SNAPPE-II)7
Extended periods of cold stress can lead to harmful side effects including delayed adaptation to extrauterine life hypoglycaemia respiratory distress hypoxia metabolic acidosis coagulation defects acute renal failure necrotizing enterocolitis failure to gain weight or weight loss and death
Many factors are associated with an increased risk of hypo-thermia These include prematurity intrauterine growth restric-tion central nervous system damage and congenital defects such as abdominal wall defects where bowel is exposed to the air
Induced cooling may help protect the brain of the asphyxiated term newborn8 but prolonged exposure to cold in babies with no brain injury must be avoided Overheating the baby with sus-pected asphyxial brain injury must also be prevented as hyper-thermia may increase the degree of damage9
Temperature control at delivery
The temperature of the fetus is between 05 and 1degC higher than that of the mother At birth the infant is exposed to a colder environment than in utero Although some heat loss may be important in stimulating onset of breathing and other adaptive mechanisms10 it is important to avoid a continuing drop in body temperature In the term baby this is achieved by drying wrapping and placing under a radiant heater if resuscitation is needed
The preterm baby often needs a period of stabilization or resuscitation and traditionally has been placed naked on a resuscitaire Despite the use of direct radiant heat studies
5 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
such as EPICure and CESDI 2728 have shown that many of these babies are cold by the time of admission to the neo-natal unit In a study from the USA of 5277 babies with a birthweight below 1500 g in the Neonatal Research Network only 108 had an admission temperature of 37 degC or above In nearly half the babies the first recorded temperature was below 36 degC Admission temperature was inversely related to mortality (28 increase per 1 degC) and late-onset sepsis There was an association of low temperature with the need for intubation at delivery suggesting that radiant heat alone had not been sufficient to offset the heat losses during prolonged resuscitation11
A baby exchanges heat with their environment by conduc-tion radiation convection and evaporation The preterm baby is at high risk of net heat loss because of a high surface area to volume ratio and increased transepidermal water loss resulting in heat lost by evaporation The normal surge in metabolic rate which occurs after birth is much reduced limiting the production of heat from the mobilization of brown fat The development in the control of skin blood flow is also delayed in the imma-ture baby reducing their ability to maintain heat by peripheral vasoconstriction12
Evaporation is the major mechanism of heat loss during resus-citation The baby will lose 560 cal for every millilitre of water evaporated from the skin (the heat of evaporation) Vohra et al have shown that using polyethylene occlusive skin wrapping around the body up to the neck during resuscitation of preterm babies under 28 weeksrsquo gestation significantly improves the central temperature on admission to the neonatal unit13 This is due to a reduction in evaporative heat losses In this random-ized study comparing rectal temperature on admission of babies wrapped at birth with those managed without wrapping body size was an important determinant of heat loss the mean rectal temperature increasing by 021degC with each 100 g increase in birthweight
The use of plastic bags leaving just the head exposed has also been found to be effective in reducing transepidermal water and heat losses during resuscitation14 It is important not to expose the skin once the baby is in the plastic bag ndash clini-cal inspection and auscultation can be done through the bag and if vascular access is needed a small hole can be cut in the plastic
Whether a plastic bag or occlusive dressing is used it is important to remember that there is still significant heat losses from the head which should be covered with a hat during resus-citation and stabilization15
Concern has been expressed about hyperthermia in some babies possibly secondary to the use of occlusive dressings or plastic bags16 Two babies in the study by Vohra et al13 had a rectal temperature above 375 degC In a small study from Edin-burgh 11 of 27 babies under 28 weeksrsquo gestation managed in plastic bags were found to have an admission temperature above 375 degC Of these eight were above this temperature from birth possibly associated with a maternal pyrexia while in the other three the temperature increased (by no greater than 06 degC) after being placed in the bag17
Preventing evaporative heat loss using occlusive dressings or plastic bags has been shown to be effective in preventing hypothermia after delivery at least in babies under 29 weeksrsquo
paeDiatRiCS anD CHilD HealtH 184 15
gestation A Cochrane review concludes that in this group con-sideration should be given to their use in the delivery suite18
No study has yet been powered to show that these treatments reduce neonatal mortality and long term outcome has not been evaluated Further large high quality randomized controlled tri-als are still needed Not least we need to confirm that the mem-brane wrapped around the infantrsquos trunk does not damage the immature skin
Transport
The transport of the newborn baby particularly the preterm infant presents many challenges Transport is not only between units but also within a hospital eg from the delivery suite to the neonatal unit or to and from the radiology department or the operating room
The most effective mode of transport within a hospital building will depend on the local configuration Newly designed neonatal units should be closely linked to the delivery suite to prevent the need for transport over long distances along draughty corri-dors A randomized controlled study comparing transfer from the delivery suite to the neonatal unit of babies under 28 weeksrsquo ges-tation using a radiant warmer or a transport incubator showed no difference in admission temperature in the two groups19 All babies in both groups had been managed with occlusive wrap-ping in the delivery room
Transfer between units is most commonly by road in an ambulance Although incubators are heated there is likely to be high radiative heat losses especially in cold weather This can be reduced by covering the incubator and by using blankets around the baby Evaporative heat losses can be reduced by using a plas-tic bag There will be high evaporative heat losses from the respi-ratory tract if ventilator gases are not heated and humidified Heated gel mattresses which warm patients through release of latent heat of crystallization can be used during transport The baby gains heat by conduction Safe use of this device is critically dependent on gel temperature at the point of activation20
Thermal care within the neonatal unit
The full-term newborn infant will maintain a normal temperature if nursed fully dressed in a cot in a warm room Recommenda-tions for optimum environmental conditions for nursing healthy infants in the newborn period have been published21
Skin-to-skin contact is an effective way of maintaining body temperature even in the very preterm infants2223
The preterm baby even if well may be unable to maintain an adequate temperature without some additional source of heat There are a variety of ways of providing this including incuba-tors radiant heaters and heated mattresses The heated gel- or water-filled mattress is very effective in helping maintain the temperature of the well preterm baby while allowing easy access for parents and staff
Clothes act as a significant thermal barrier to heat loss New-born infants needing intensive or high dependency care are often nursed naked to allow close observation and easy access for examination and treatment This significantly affects tempera-ture control as the resistance to heat loss of a naked baby is three times less than that of a clothed wrapped infant2425
6 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Control of the thermal environment is important for all babies but it is the unwell immature babies who present the greatest challenge They are usually nursed either in an incubator or on an open platform under a radiant heater The early clinical trials of Silverman and others showed that the use of incuba-tors to keep babies warm improved outcome There have never been any controlled studies that show that radiant heaters are as effective clinically Babies nursed with similar skin temperatures have a higher basal metabolic rate when managed under radi-ant heaters compared with incubators26 However no study has shown any significant difference in outcome for babies nursed using either of these devices although Meyer et al27 reported a non-significant trend to better outcome in babies nursed under a radiant heater
Transepidermal water loss
Silverman in the 1950s showed that babies are better able to maintain their body temperature in a humid environment com-pared with a dry environment28
In the 1970s it became possible to measure the evaporation rate of water from the skin surface29 Transepidermal water losses (TEWL) are high in the immature baby At 26 weeksrsquo gestation on day 1 of life the baby can lose over 50 kcalkg by evapora-tion compared with less than 5 kcalkg in the term infant30 Data from Hammerlund et al30 suggest that the skin matures rapidly after birth and adult losses are reached around 10 d of age in all babies After this time the major source of heat loss in all babies is from radiation More recently others have shown that in the very immature baby the maturation of the skin may take longer and 30 weeksrsquo corrected age is a better estimate of the time taken to reach adult TEWL31 In practical terms the amount of trans-epidermal fluid losses after about 14 d are unlikely to remain a major problem
Evaporative water loss from the skin depends on the ambi-ent water vapour pressure irrespective of how the baby is being nursed The high rate of evaporation during care under a radiant heater is due to the low ambient water vapour pressure and not any direct effect of non-ionizing radiation on the skin32
TEWL results in loss of both heat and fluid Under a radi-ant heater the temperature of the baby is maintained because of radiant heat gain but the large fluid losses can be a seri-ous problem Various interventions can help reduce evaporative fluid losses mainly from the skin but also from the respiratory tract
IncubatorsWithin an incubator it is relatively easy to raise the ambient water vapour pressure by introducing humidity within the can-opy The use of a relative humidity of 80 for the first 7ndash10 d of life significantly reduces TEWL in even the most immature infant30 Modern designs use a sealed water system to produce the humidity minimizing the concerns about possible increased infection risk in humidified incubators
Opening the incubator portholes results in a rapid fall in humidity although the air temperature within the canopy is maintained The handling of babies within incubators has been shown to be associated with increased thermal stress33 and it is likely that this is due to the fall in environmental humidity
paeDiatRiCS anD CHilD HealtH 184 15
resulting in increased evaporative heat losses Increasing the air temperature will compensate for the heat loss but incubators are relatively slow to respond to such changes
High humidity within the incubator can cause lsquorain outrsquo on the inside of the canopy This is caused by water condensing on the cold walls and can be minimized by ensuring an adequate environmental temperature within the nursery (around 28 degC)
Radiant heatersTEWL is the major problem in babies nursed under radiant heaters A shield or plastic blanket can be used to cover the baby and create a humidified microenvironment Warm humid-ified air can be passed under the shield or blanket but care must be taken to control the temperature and to make sure it does not affect the skin servo probe attached to the baby If the cover is removed the humidity falls rapidly and the baby starts to lose large amounts of fluid The radiant heater will compen-sate for any fall in the babyrsquos temperature but fluid losses are a concern
Maintenance of skin integrityDamage to the fragile skin of the preterm baby occurs easily and results in a significant increases both in TEWL and the risk of infection Maintaining skin integrity is very important and any adhesives on the skin should be kept to a minimum
Skin coveringsTransparent adhesive dressings on the skin reduce fluid loss but cause significant damage making them impractical
Use of semipermeable non-adhesive dressings lowers TEWL and reduces the bacteria number in the covered skin34 In a ran-domized controlled trial in infants less than 1000 g the skin cov-ered with a semipermeable membrane was in better condition but there were no significant differences in fluid requirements or electrolyte status35
Emollients are used to cover the skin and prevent fluid loss They have been shown to be safe and do not cause burns when exposed to radiant heat or phototherapy Their use reduces excessive drying skin cracking and fissuring However the effect of these products wears off after about 3 h necessitating repeated application36 Treated infants had better skin scores and there were no differences in bacterial skin counts fungal counts or colonization patterns or fluid requirements and electrolyte status37
Ventilator humidityThere can be high fluid and heat losses from the respiratory tract of the ventilated baby It is important to use adequate humidifi-cation in all ventilator circuits
PhototherapyThe effect of phototherapy on TEWL is variable No change was found in a group of thermally stable infants38 yet others have reported an increase in TEWL despite skin temperature and rela-tive humidity remaining unchanged39 Rather than increase fluid intake just because phototherapy has been started fluid balance should be individually monitored and adjusted if necessary
Modern phototherapy units produce little heat but there is still some increase in the temperature of the top of the incubator
7 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
canopy This will reduce radiative heat losses and the incubator air temperature may have to be reduced to prevent a rise in the babyrsquos temperature
Transepidermal water loss and skin maturationTransepidermal movement of water is essential for the acceler-ated maturation of the skin of the immature baby40 It also helps in maintaining the epidermal barrier function41
Use of high ambient humidity in nursing preterm babies under 28 weeksrsquo gestation has been shown to reduce the rate of promo-tion of skin barrier development42
More work in the immature baby is needed to determine the optimum level and duration of environmental humidity as well as the associated benefits and risks of use and the effects of humidification on clinically important outcomes43
Temperature monitoring and its interpretation
The concept of the neutral thermal environment in which a baby uses a minimum of energy to maintain thermal stability has proven useful in determining the optimum environmental temperature for nursing the newborn baby4445 The published data are now old and do not include any allowance for added humidity This makes them less useful in the care of the very immature baby
The way a baby interacts with their environment is always changing and whatever settings are first used it is necessary to monitor continuously the thermal balance Continuous mea-surement of oxygen consumption to allow calculation of energy expenditure is not practical and in normal day-to-day care tem-perature monitoring is the only means of assessing the thermal stability of the baby
There is no single deep body temperature as this will vary depending on the metabolic rate of a particular tissue The brain has the highest temperature of any organ within the body It is however possible to find a central temperature that is representa-tive of deep body temperature Trends in this temperature reflect changes in the deep body temperatures of the body at least with sufficient accuracy for day-to-day clinical care
Traditionally rectal temperature has been used as the mea-sure of deep body temperature This is still used commonly in many countries but less so in UK There is a significant risk of damage to the mucosa of the rectum Also rectal temperature is unreliable being affected by the depth of insertion of the ther-mometer whether the baby has just passed a stool and by the temperature of the blood returning from the lower limbs It is difficult to retain the probes in the same position making this an unreliable site for continuous temperature monitoring
The temperature in the oesophagus at the level of the heart gives a measure of the temperature of the blood in the great veins returning from the body This is possibly the best overall representation of the lsquodeep body temperaturersquo Measurement of oesophageal temperature is however very invasive and not suit-able for clinical monitoring
The temperature of the skin over the liver or in the axilla reflects central temperature Actual values will be lower than the deep body temperatures but in the immature baby these sites can be used to show the trend in central temperature A more accurate measurement can be obtained by placing the
paeDiatRiCS anD CHilD HealtH 184 15
probe between the scapulae and a non-conducting mattress No tape is needed on the skin as the baby lies on the probe holding it in place If the probe is over an area of skin from which no heat can be lost by conduction convection radia-tion or evaporation then with heat flow from the centre of the body to the skin down a temperature gradient this area of skin will warm up to the same temperature as the bodyrsquos core This so-called zero heat flux temperature has been shown to be very close to the central temperature as measured by an oesophageal probe46
The measurement of a single temperature tells us how well the baby is maintaining that temperature but nothing about how much energy is being used to achieve thermal balance The continuous measurement and display of a central (abdominal axilla or zero heat flux) and a peripheral (sole of the foot) tem-perature detects cold stress with the peripheral temperature fall-ing before the central measurement changes
The preterm baby who appears to be comfortable in their environment will have a central temperature measured from a skin probe of 368ndash373 degC and a centralndashperipheral temperature difference of 05ndash1 degC An increasing centralndashperipheral tempera-ture difference particularly above 2 degC is usually due to cold stress and occurs before any fall in central temperature12
Hypovolaemic babies will vasoconstrict their peripheral circu-lation in an attempt to maintain blood pressure This results in an increase in the centralndashperipheral temperature difference but in such cases there are usually other signs of hypovolaemia such as rising heart rate and falling blood pressure12
A high central temperature particularly if unstable along with a wide centralndashperipheral gap is seen in septic babies47
Conclusion
Although we have known for a very long time the importance of maintaining the temperature of the newborn we are still faced with new challenges in the care of the sick immature baby Tem-perature control during their period of adaptation to extrauterine life is often poor and allowing these vulnerable babies to cool is associated with adverse outcome Simple measures can prevent hypothermia following delivery If cold at birth is associated with poor outcome there is no reason to believe that preventing ther-mal stress is any less important once the baby is in the neonatal unit It is important that the risks and benefits associated with various methods of controlling the infantrsquos temperature are fully understood
RefeRenCeS
1 Cone te perspectives in neonatology in Sith gF Vidyasagar D eds
Historical Review and Recent advances in neonatal and perinatal
medicine mead Johnson nutritional Division 1983 p 9ndash33
2 Silverman Wa Fertig JW Berger ap the influence of the thermal
environment upon survival of newly born preterm infants Pediatrics
1958 22 876ndash885
3 Silverman Wa agate FJ Fertig JW a sequential trial of the
nonthermal effect of atmospheric humidity on survival of human
infants of low birth weight Pediatrics 1963 31 710ndash724
8 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
4 Costeloe K Hennessy e gibson at marlow n Wilkinson aR for the
epiCure Study group the epiCure study outcomes to discharge
from hospital for infants born at the threshold of viability Pediatrics
2000 196 659ndash671
5 CeSDi project 2728 available from wwwcemachorguk
publicationsp2728mainreportpdf
6 parry g tucker J tarnow-mordi W for the uK neonatal Staffing
Study Collaborative group CRiB ii an update of the clinical risk
index for babies score Lancet 2003 361 1789ndash1791
7 Richardson DK Corcoran JD escobar gJ et al Snap-ii and Snappe-ii
simplified newborn illness severity and mortality risk scores
J Pediatr 2001 138 92ndash100
8 Wyatt JS gluckman pD liu py et al CoolCap Study group
Determinants of outcomes after head cooling for neonatal
encephalopathy Pediatrics 2007 119 912ndash921
9 yager Jy armstrong ea Jaharus C Saucier Dm Wirrell eC preventing
hyperthermia decreases brain damage following neonatal-ischemic
seizures Brain Res 2004 1011 48ndash57
10 Harned Jr HS Herrington Rt Ferreiro Ji the effects of immersion
and temperature on respiration in newborn lambs Pediatrics 1970
45 598ndash605
11 laptook aR Salhab W Bhaskar B neonatal Research network
admission temperature of low birth weight infants predictors and
associated morbidities Pediatrics 2007 119 e643ndash649
12 lyon aJ pikaar me Badger p mcintosh n temperature control in
infants less than 1000g birthweight in the first 5 days of life Arch
Dis Child 1997 76 F47ndash50
13 Vohra S Roberts RS Zhang B Janes m Schmidt B Heat loss
prevention (Help) in the delivery room a randomized controlled
trial of polyethylene occlusive skin wrapping in very preterm infants
J Pediatr 2004 145 750ndash753
14 lyon aJ Stenson B Cold comfort for babies Arch Dis Child Fetal
Neonatal Ed 2004 89 F93ndash94
15 Stothers JK Head insulation and heat loss in the newborn Arch Dis
Child 1981 56 530ndash534
16 newton t Watkinson m preventing hypothermia at birth in
preterm babies at a cost of overheating some Arch Dis Child Fetal
Neonatal Ed 2003 88 F256
17 Smith Cl Quine D mcCrosson F armstrong l lyon a Stenson B
Changes in body temperature after birth in preterm infants
stabilised in polythene bags Arch Dis Child Fetal Neonatal Ed 2005
90 F444
18 mcCall em alderdice Fa Halliday Hl Jenkins Jg Vohra S
interventions to prevent hypothermia at birth in preterm andor low
birthweight babies Cochrane Database of Systematic Reviews 2005
issue 1 art noCD004210 doi10100214651858CD004210pub2
19 meyer mp Bold gt admission temperatures following radiant
warmer or incubator transport for preterm infants lt 28 weeks
a randomised study Arch Dis Child Fetal Neonatal Ed 2007 92
F295ndash297
20 Carmichael a mcCullough S Kempley St Critical dependence of
acetate thermal mattress on gel activation temperature Arch Dis
Child Fetal Neonatal Ed 2007 92 F44ndash45
21 Hey en the care of babies in incubators in gairdner D Hull D
eds Recent advances in paediatrics 4th edn london J amp a
Churchill 1971 p 171ndash216
22 Whitelaw a Heisterkamp g Sleath K acolet D Richard m Skin-to-
skin contact for very low birthweight infants and their mothers Arch
Dis Child 1988 63 1377ndash1381
paeDiatRiCS anD CHilD HealtH 184 15
23 Bauer K pyper a Sperling p uhrig C Versmold H effects of
gestational and postnatal age on body temperature oxygen
consumption and activity during early skin-to-skin contact between
preterm infants of 25ndash30-week gestation and their mothers Pediatr
Res 1998 44 247ndash251
24 Hey en Katz g orsquoConnell B the total thermal insulation of the
newborn baby J Physiol 1970 207 683ndash689
25 Hey en temperature regulation in sick infants in tinker J Rapin m
eds Care of the Critically ill patient Berlin Springer 1983 p
1013ndash1029
26 leBlanc mH Relative efficacy of an incubator and an open warmer
in producing thermoneutrality for the small premature infant
Pediatrics 1982 69 439ndash445
27 meyer mp payton mJ Salmon a Hutchinson C deKlerk a
a clinical comparison of radiant warmer and incubator care for
preterm infants from birth to 1800grms Pediatrics 2001 108
395ndash401
28 Silverman Wa Blanc Wa effect of humidity on survival of newly
born premature infants Pediatrics 1957 20 477ndash487
29 Hammarlund K Sedin g transepidermal water loss in newborn
infants iii relation to gestational age Acta Paediatr Scand 1979
68 795ndash801
30 Hammerlund K Stroumlmberg B Sedin g Heat loss from the skin of
preterm and fullterm newborn infants during the first weeks after
birth Biol Neonate 1986 50 1ndash10
31 Kalia yn nonata lB lund CH guy RH Development of skin
barrier function in premature infants J Invest Dermatol 1998 111
320ndash326
32 Kjartansson S arsan S Hammarlund K Sjoumlrs g Sedin g Water loss
from the skin of term and preterm infants nursed under a radiant
heater Pediatr Res 1995 37 233ndash238
33 mok Q Bass Ca Ducker Da mcintosh n temperature instability
during nursing procedures in preterm neonates Arch Dis Child
1991 66 783ndash786
34 mancini aJ Sookdeo-Drost S madison KC Smoller BR lane at
Semipermeable dressings improve epidermal barrier function in
premature infants Pediatr Res 1994 36 306ndash314
35 Donahue ml phelps Dl Richter Se Davis Jm a semipermeable skin
dressing for extremely low birth weight infants J Perinatol 1996 16
20ndash26
36 nopper aJ Horii Ka Sookdeo-Drost S Wang tH mancini aJ lane at
topical ointment therapy benefits premature infants J Pediatr 1996
128 660ndash669
37 pabst RC Starr Kp Qaiyumi S Schwalbe RS gewold iH the effect
of application of aquaphor on skin condition fluid requirements
and bacterial colonization in very low birth weight infants
J Perinatol 1999 19 278ndash283
38 Kjartansson S Hammarlund K Sedin g insensible water loss from
the skin during phototherapy in term and preterm infants Acta
Paediatr 1992 81 764ndash768
39 grunhagen DJ de Boer mg de Beaufort aJ Walther FJ
transepidermal water loss during halogen spotlight phototherapy in
preterm infants Pediatr Res 2002 51 402ndash405
40 Hanley K Jiand y elias pm Feingold KR Williams ml acceleration
of barrier ontogenesis in vitro through air exposure Pediatr Res
1997 41 293ndash299
41 Denda m Sato J masuda y et al exposure to a dry environment
enhances epidermal permeability barrier function J Invest Dermatol
1998 111 858ndash863
9 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
42 Aringgren J Sjoumlrs g Sedin g ambient humidity influences the rate of
skin barrier maturation in extremely preterm infants J Pediatr 2006
148 613ndash617
43 Sinclair l Sinn J Higher versus lower humidity for the prevention of
morbidity and mortality in preterm infants in incubators (protocol)
Cochrane Database Syst Rev 2007 issue 2 art noCD006472
doi10100214651858
44 Hey en Katz g the optimum thermal environment for naked
babies Arch Dis Child 1970 45 328ndash334
45 Sauer pJJ Dane HJ Visser HKa new standards for neutral thermal
environment of healthy very low birthweight infants in week one of
life Arch Dis Child 1984 59 18ndash22
46 Dollberg S Xi y Donnelly mm a noninvasive alternative to rectal
thermometry for continuous measurement of core temperature in
the piglet Pediatr Res 1993 34 512ndash517
47 messaritakis J anagnostakis D laskari H Katerelos C Rectal-skin
temperature difference in septicaemic newborn infants Arch Dis
Child 1990 65 380ndash382
paeDiatRiCS anD CHilD HealtH 184 16
Practice points
bull Hypothermia in the newborn infant is associated with adverse
outcome
bull Despite improvements in technology the preterm baby is still
at high risk of hypothermia immediately after delivery
bull prevention of evaporative heat losses eliminates hypothermia
at resuscitation
bull High evaporative fluid losses must be prevented if the baby
is nursed under a radiant heater
bull more studies are needed to determine the optimum
management after delivery and to show if reducing
transepidermal water loss has an effect on the rate of skin
maturation
bull Continuous monitoring and display of a central and peripheral
temperature gives early warning of developing cold stress
0 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemiaJ m Hawdon
Abstractat birth the newborn baby undergoes many adaptive changes to inde-
pendent extrauterine life these include the changes of metabolic adap-
tation which must be understood in order to identify and manage the
conditions in which metabolic adaptation is delayed impaired or fails
resulting in low levels of glucose and other metabolic fuels which in turn
affect neonatal neurological function and if prolonged and severe cause
potential adverse outcome Babies identified as at risk of impaired met-
abolic adaptation must undergo clinical monitoring including accurate
blood glucose monitoring tailored to their condition Babies who present
with abnormal clinical signs in association with a low blood glucose level
must be investigated for underlying cause and treated promptly preven-
tion and treatment of clinically significant hypoglycaemia must be planned
to avoid compromising successful establishment of breast feeding
Keywords alternative fuels blood glucose breast feeding neonatal
metabolic adaptation operational thresholds risk factors
Introduction
At birth the newborn baby undergoes many adaptive changes to independent extrauterine life These include the changes of met-abolic adaptation essential to ensure energy provision to vital organs and then to sustain growth and further development The changes involved in metabolic adaptation must be understood in order to identify and manage the conditions in which metabolic adaptation is delayed impaired or fails The clinical outcome of these circumstances is usually referred to with the single short-hand diagnostic term lsquoneonatal hypoglycaemiarsquo However as will be illustrated in this article it is not appropriate to ascribe a diagnostic label to neonatal hypoglycaemia first because glucose is not the only fuel in the neonatersquos fuel economy and second because hypoglycaemia is the consequence of a number of vari-ous underlying disorders and thus does not in itself warrant a diagnostic label
There have been extensive studies of metabolic adaptation in human neonates and neonatal non-human mammals The latter studies have identified those mammals most similar to humans
J M Hawdon MA MBBS MRCP FRCPCH PhD is Consultant Neonatologist and
Honorary Senior Lecturer at UCL EGA Institute for Womenrsquos Health
Elizabeth Garrett Anderson and Obstetric Hospital University College
London Hospitals NHS Foundation Trust Huntley Street London UK
paeDiatRiCS anD CHilD HealtH 184 161
in terms of metabolic adaptation and sought to compare nutri-tionally comparable time frames eg suckling versus weaning periods Whilst the processes of metabolic adaptation are well described in term and preterm human neonates there are few if any clinical studies in human neonates of sufficient rigour to provide evidence for the circumstances in which brain injury may occur and thus it is not possible to provide evidence-based guide-lines for the prevention and management of clinically significant hypoglycaemia Therefore recommendations in this article and in the referenced review articles by recognized experts remain pragmatic and urge clinicians to individualize management for each baby placing heavy emphasis on careful clinical evaluation rather than single numerical definitions of brain-injuring hypogly-caemia and on detecting and treating underlying pathologies1ndash6
Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
During intrauterine life the fetus receives via the placenta a con-stant supply of nutrients initially for growth but in the third tri-mester also for storage Glucose crosses the healthy placenta at a rate of approximately 5 mgkgmin In addition to that required for basal fetal metabolism glucose is converted to glycogen which is stored in the liver cardiac muscle and central nervous system In the third trimester excess glucose is converted to tri-glycerides which are stored in adipose tissue
Insulin is an important fetal hormone to ensure glucose and other substrates are utilized for growth and storage but in nor-mal circumstances insulin is not required for fetal glucose con-trol The exception is for the infant of the mother with poorly controlled diabetes when transfer of glucose across the placenta is at a higher rate driven by the maternalndashfetal concentration gra-dient This results in increased insulin secretion excess growth and increased storage of glycogen and adipose tissue (macroso-mia) along with increased risk of intracellular hypoxia
Conversely in the fetus affected by severe placental insuffi-ciency transfer of glucose and other nutrients across the placenta is at a lower rate and the fetus is required to metabolize first its own fuel stores and then structural proteins (eg in muscle) to ensure energy delivery to the vital organs assisted by the redis-tribution of blood flow to these organs Should placental function deteriorate further these adaptive responses fail Fetal hypogly-caemia has been described in these circumstances78
When placental nutrition abruptly ceases at birth the healthy neonate is dependent upon endocrine changes to initiate meta-bolic adaptation Insulin levels fall steadily and the action of any residual circulating insulin is overcome by the surge of the coun-ter-regulatory hormones glucagon and the catecholamines This change in the balance of glucoregulatory hormones induces the activity of key enzymes for glycogenolysis (release of glucose from glycogen stores) gluconeogenesis (production of glucose from precursors including glycerol and amino acids) lipolysis (release of free fatty acids and glycerol from adipose tissue stores) and beta-oxidation of fatty acids to produce ketone bodies910 If fasting is prolonged structural protein is broken down to release gluconeogenic amino acids Other than lipolysis and proteolysis all of these processes take place in the liver Glycogenolysis also takes place in cardiac muscle and the central nervous system providing immediate energy (in the form of glucose or lactate)
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
at this crucial time411 Clearly during this catabolic phase of immediate postnatal nutrition prior to the establishment of suck-ling feeds provision of energy for vital organ function is at the expense of growth and fuel storage
The postnatal metabolic transition is characterized by low cir-culating blood glucose concentrations compared to those of older infants and children often for a number of days12 This is almost always of no pathological significance for a number of reasons including differences in the function and metabolic requirements of the brain and importantly the production and utilization of alter-native fuels lactate and ketone bodies which are in plentiful supply in the neonate341213ndash20 An important finding from clinical studies and of clinical relevance to those caring for mothers and babies is that in all groups of infants studied to date those who are breast fed have higher circulating ketone body levels than those who are formula fed even after correcting for blood glucose levels102122
There are circumstances however when hypoglycaemia is severe and prolonged and conditions when alternative fuel pro-duction is also impaired or fails In these circumstances low blood glucose levels do acquire clinical significance The key metabolic processes and the risk factors for impaired metabolic adaptation are summarized in Table 1
Metabolic changes at birth ndash key hormones and metabolic processes and risk factors for impaired metabolic adaptation
Postnatal metabolic
changes
Risk factors
Hormones
insulin falls neonatal hyperinsulinism ndash infant of
diabetic mother or idiopathic
glucagon surge possibly blunted by iv glucose or
formula feeds
Catecholamine surge maternal beta-blocker medication
(Cortisol ndash weak effect) (pituitary or adrenal insufficiency)
Metabolic processes
glygogenolysis preterm intrauterine growth
restriction (iugR) ndash reduced stores
perinatal hypoxia-ischaemia ndash stores
utilized
Hyperinsulinism
maternal beta-blocker medication
glycogen storage disorders
gluconeogenesis Hyperinsulinism
maternal beta-blocker medication
Hepatic dysfunction
Very rare inborn errors of metabolism
lipolysis preterm iugR ndash reduced stores
Hyperinsulinism
maternal beta-blocker medication
Ketogenesis Defects of beta-oxidation of fatty
acids
Hepatic dysfunction
Table 1
paeDiatRiCS anD CHilD HealtH 184 16
Impaired metabolic adaptation
Risk factors for impaired metabolic adaptation vary and may be related to any of the following reduced body fuel stores failure of the normal endocrine changes at birth systemic illnesses which impede function of the liver where the key metabolic processes occur or rarely inborn errors of metabolism (see Table 1)
It is well recognized that significant hypoglycaemia will result in a reduced level of consciousness andor fits However it is always important to be alert for detect and treat an underlying pathology which could be causing both the hypoglycaemia and the abnormal signs Often abnormal signs and hypoglycaemia are co-morbidities eg a primary neurological problem causes both abnormal neurological signs and hypoglycaemia secondary to poor feeding For this reason all possible underlying causes for presentation with hypoglycaemia must be considered and investigations planned accordingly Investigations for inborn errors of metabolism and endocrine disorders are most informa-tive if carried out when blood glucose levels are low
There have been extensive efforts to use data from clinical stud-ies of the human neonate to determine the significance of neonatal hypoglycaemia in terms of neurophysiological neurodevelopmental and neuroradiological sequelae However there are major difficul-ties in interpreting these clinical studies as to date these have been flawed by confounding factors such as immaturity placental insuf-ficiency and co-existing complications by heterogeneity of subjects and by failure to take into account protective mechanisms11423 The evidence from both animal and human studies suggests lsquopurersquo hypo-glycaemic brain injury is rare and for hypoglycaemic brain injury to occur there must be co-existing failure of metabolic adaptation such that alternative fuels are not available There is no evidence that lsquotransitionalrsquo hypoglycaemia in the healthy neonate is associated with acute or long term sequelae and indeed even for babies in the at-risk groups on many occasions protective factors will prevail
Diagnosis of clinically significant hypoglycaemia
lsquoNeonatal hypoglycaemiarsquo is a commonly cited diagnosis most often based on a single blood glucose level and using inaccurate methods of measurement and with disregard for the presence or absence of associated clinical signs In the many published texts and local guidelines there is no consistency of approach For this reason a multinational group of experts attempted to examine critically the evidence on which clinical recommendations should be made1 Fol-lowing detailed analysis the authors considered it impossible to define hypoglycaemia as a single blood glucose level and instead suggested operational thresholds and therapeutic goals They con-cluded that low blood glucose levels accompanied by neurological signs should be investigated and treated regardless of the blood glu-cose level They also pragmatically concluded that a blood glucose level below 10 mmollitre should be treated immediately In babies who are at risk of impaired metabolic adaptation but who have no clinical signs it is recommended that interventions to raise blood glucose level are considered if blood glucose levels are persistently below 20 mmollitre For sick and very low birthweight babies who are likely to have a requirement for intravenous glucose there should be a lsquotherapeutic goalrsquo to maintain blood glucose levels above 25 mmollitre Where there is known hyperinsulinism (a very high-risk condition characterized by high intravenous glucose
2 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
requirements to maintain normoglycaemia) an operational thresh-old and therapeutic goal of 35 mmollitre has been proposed24
Finally there must be careful consideration of the infant of the diabetic mother In extreme and rare cases there may be signifi-cant but transient hyperinsulinism and in these cases the thera-peutic goal must be 35 mmollitre More commonly babies whose mothersrsquo diabetes has been well controlled will have normal lsquotran-sitional hypoglycaemiarsquo or slightly delayed metabolic adaptation while insulin levels fall postnatally There must be careful and repeated clinical assessment including blood glucose monitoring For infants of diabetic mothers who have no evidence of signifi-cant hyperinsulinism and no abnormal clinical signs there is no evidence that the operational threshold for hyperinsulinism must be applied Indeed to do so would result in separation of large numbers of healthy babies from their mothers with the conse-quent impact upon breast feeding and resource allocation25
The operational thresholds for various groups of babies are summarized in Table 2
The guidance relating to operational thresholds is predicated upon the accurate measurement of blood glucose levels It is now well known that the commonly used reagent strips are insufficiently accurate to diagnose hypoglycaemia and monitor at-risk infants and there must be access to equipment which allows immediate and accurate determination of blood glucose levels1426ndash28
Blood glucose monitoring
An accurate method for blood glucose monitoring must be employed as described above The sample should be free flowing venous or from a warm heel such that the blood flows freely without squeezing
Blood of high haematocrit often yields low blood glucose lev-els because of dilution of glucose by red cell water However this is also clinically relevant because polycythaemia is itself a high-risk situation Therefore in polycythaemic infants both the haematocrit and blood glucose level must be monitored and both acted upon accordingly
Operational thresholds for blood glucose levels in the management of babies at risk of impaired metabolic adaptation124
Clinical condition Blood glucose level at which
to consider intervention and
therapeutic goal
all at-risk babies lt10 mmollitre
abnormal neurological
signs
intervene regardless of blood
glucose levelSystematically unwell baby therapeutic goal of 25 mmollitre
at-risk babies no abnormal
neurological signs
persistently lt20 mmollitre
Hyperinsulinism 35 mmollitre
Table 2
paeDiatRiCS anD CHilD HealtH 184 163
Only babies in at-risk groups or babies who have abnormal neurological signs should be subjected to blood glucose monitor-ing (Table 3)
It is important not to commence blood glucose monitoring too soon after birth as to do so would fail to differentiate the baby with incipient hypoglycaemia from the baby undergoing the nor-mal postnatal fall in blood glucose level It is recommended in the otherwise healthy but at-risk baby to wait until around 3 h after birth to make the first blood glucose estimation2528 In prac-tice this is usually before the second feed assuming best practice of offering a baby a breast (or if necessary formula feed) imme-diately after birth Clearly if the baby is unwell or has abnormal clinical signs in the first 3 h they will be treated according to clinical condition which will include intravenous fluids and the therapeutic goal described above would apply
Similarly the temptation to measure blood glucose level shortly (within 2 h) after intravenous glucose has been discon-tinued must be avoided In this circumstance as at birth blood glucose levels fall and then subsequently rise in response to coun-ter-regulation It is this effective rise which must be assessed by blood glucose measurement at least 2 h after a change is made (provided the baby remains clinically well)
Blood glucose levels rise after a feed and fall to a nadir before the subsequent feed As our concern is the lowest blood glucose level during the feed cycle and as this measurement may assist in determining best feed frequency it is important that pre-feed blood glucose concentration is measured There is no clinical value in measuring a post-feed blood glucose level as this may be falsely reassuring and this practice subjects babies to more frequent heel pricks or venesections than is necessary
Finally consideration must be given to when to discontinue blood glucose monitoring This will depend upon the babyrsquos clin-ical condition feeding pattern and underlying disorder or risk factors for impaired metabolic adaptation
Prevention and management of clinically significant hypoglycaemia
In babies at risk of clinically significant hypoglycaemia and who are well enough to tolerate enteral feeds milk feeds are the
At-risk babies for whom blood glucose monitoring is recommended
abnormal neurological signs
Systemically unwell eg suspected or proven infection
hypoxicndashischaemic encephalopathy
preterm (lt 37 weeks)
intrauterine growth restriction (lt 2nd centile and any baby with
signs of wasting)
infant of diabetic mother
polycythaemia
maternal beta-blocker medication
Suspected hyperinsulinism
Suspected inborn error of metabolism or endocrine disorder
Table 3
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
mainstay of prevention For babies who are able to feed orally breast feeding should be first choice and there must be maximal support for the mother to do so This is a key clinical priority for midwives and paediatricians
If there are concerns regarding adequacy of breast feeding to prevent hypoglycaemia the mother should be encouraged to commence expression of milk from very soon after birth If there is insufficient breast milk to prevent babies reaching the opera-tional thresholds described above there should be judicious use of formula milk using only the smallest amount required to keep the babyrsquos glucose in the required range Formula milk in exces-sive quantities has been demonstrated to suppress normal meta-bolic adaptation2122
In babies for whom early enteral feeds are not appropriate or not tolerated or for whom enteral feeding does not prevent blood glucose level falling below operational thresholds intravenous glucose infusion at rates around 4ndash5 mgkgmin (58ndash72 mlkgd of 10 dextrose) are usually sufficient to prevent hypoglycae-mia If blood glucose levels remain below therapeutic goals the rate of infusion may be steadily increased Excess glucose infu-sion over and above that required to maintain the therapeutic goal will stimulate insulin and there is a risk of rebound hypo-glycaemia if high rate glucose infusions are too rapidly reduced Milk feeds if tolerated should be continued if intravenous glu-cose is commenced
If infused volume of glucose solution becomes excessive in order to maintain therapeutic goals or if fluid restriction must be applied more concentrated glucose concentrations must be infused through a central venous line This is particularly rel-evant to the hyperinsulinaemic baby in whom glucose infusion rates in excess of 8ndash10 mgkgmin are required to maintain ther-apeutic goals There is a high risk of severe and brain-damaging hypoglycaemia if treatment is delayed or fails to raise blood glu-cose levels and management of these babies requires consulta-tion with or referral to a specialist centre24
If there is presentation of hypoglycaemia with abnormal clinical signs or a very low blood glucose level (less than 1 mmollitre) this mandates urgent treatment with intravenous glucose The rates of glucose infusion described above are usually sufficient to bring the blood glucose level rapidly to the therapeutic goal without a bolus of glucose being necessary In fact a bolus dose of glucose will result in a peak blood glucose level and then an insulin surge making subsequent management problematical This is minimized by the use of a lsquomini-bolusrsquo should a bolus of glucose be required ndash 200 mg glucosekg (2 mlkg of 10 dextrose)28 Indications for mini-bolus are infants presenting with fits or coma or an lsquounre-cordablersquo or zero blood glucose level A mini-bolus should always be followed with glucose infusion or an increased glucose infusion rate if a baby already receiving intravenous glucose has required a mini-bolus
The temptation to supplement enteral feeds with glucose polymers and energy supplements (eg Duocal) or to use oral glucose gels or solutions (eg Hypostop) should be avoided as this carries a risk of necrotizing enterocolitis is likely to suppress normal metabolic adaptation and will suppress the appetite of the baby for effective oral feeding
Finally there are additional medications which may be employed in specific circumstances (Table 4) More detailed descriptions are given elsewhere242728 Babies who have hypoglycaemia which
paeDiatRiCS anD CHilD HealtH 184 164
is difficult to control by the measures described above and who require these additional treatments should be cared for in a centre which has expertise in metabolic and endocrinological conditions
Summary
Much controversy and confusion has surrounded neonatal hypo-glycaemia but this usually arises as a result of failure to under-stand the processes of normal metabolic adaptation and the fact that hypoglycaemia is a presenting sign rather than a diagnosis in itself Plans for investigation and management must be based upon the most likely underlying cause of impaired metabolic adaptation and take into account the clinical condition of the baby This is counter to the current trend to propose rigid pro-tocols and algorithms and re-introduces the value of detailed clinical evaluation and decision making The mainstay of man-agement is close clinical observation of vulnerable infants and energy provision tailored to their individual needs whilst avoid-ing excessively invasive management (namely unnecessary sep-aration of mother and baby routine or excessive formula milk supplementation or intravenous glucose administration) which themselves inhibit protective metabolic responses and impede successful establishment of breast feeding
ReFeRenCeS
1 Cornblath m Hawdon Jm Williams aF et al Controversies regarding
definition of neonatal hypoglycemia Suggested operational
thresholds Pediatrics 2000 105 1141ndash1145
2 Cornblath m ichord R Hypoglycemia in the neonate Semin
Perinatol 2000 24 136ndash149
3 Vannucci RC Vannucci SJ Hypoglycaemic brain injury Semin
Neonatol 2001 6 147ndash155
4 Rozance pJ Hay WW Hypoglycaemia in newborn infants features
associated with adverse outcomes Biol Neonate 2006 90 74ndash86
5 Hawdon Jm Hypoglycaemia in newborn infants defining the
features associated with adverse outcomes ndash a challenging remit
Biol Neonate 2006 90 87ndash88
6 Williams aF neonatal hypoglycaemia clinical and legal aspects
Semin Fetal Neonatal Med 2005 10 363ndash368
7 Soothill pW nicolaides KH Campbell S prenatal asphyxia
hyperlacticaemia hypoglycaemia and erythroblastosis in growth
retarded fetuses BMJ 1987 294 1051ndash1053
Additional medication in specific conditions (if these are required there must also be referral to a specialist centre)
Medication Indication
glucagon intramuscular bolus dose of 200 μgkg
transient rise in blood glucose level eg
when difficulty re-siting intravenous infusion
Diazoxide Hyperinsulinism
Hydorcortisone pituitary or adrenal insufficiency
Table 4
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
8 Hawdon Jm Ward platt mp mcphail S Cameron H Walkinshaw Sa
prediction of impaired metabolic adaptation by antenatal Doppler
studies in small for gestational age fetuses Arch Dis Child 1992
67 787ndash792
9 Deshpande S Hawdon Jm et al adaptation to extrauterine life in
Rodeck C Whittle m eds Fetal medicine Basic Science and Clinical
practice edinburgh Churchill livingstone 1999
10 Ward platt m Deshpande S metabolic adaptation at birth Semin
Fetal Neonatal Med 2005 10 341ndash350
11 eyre Ja Stuart ag Forsyth RJ Heaviside D Bartlett K glucose
export from the brain in man evidence for a role for astrocytic
glycogen as a reservoir of glucose for neural metabolism Brain Res
1994 28 349ndash352
12 Hawdon Jm Ward platt mp aynsley-green a patterns of metabolic
adaptation for preterm and term infants in the first neonatal week
Arch Dis Child 1992 67 357ndash365
13 Hawdon Jm Ward platt mp aynsley-green a prevention and
management of neonatal hypoglycaemia Arch Dis Child Fetal
Neonatal Ed 1994 70 F60ndash64
14 Hawdon Jm Hypoglycaemia and the neonatal brain Eur J Paediatr
1999 158 S9ndash12
15 massieu l Haces ml montiel t Hernaacutendez-Fonseca K acetoacetate
protects hippocampal neurons against glutamate-mediated neuronal
damage during glycolysis inhibition Neuroscience 2003 120
365ndash378
16 yamada Ka Rensing n thio ll Ketogenic diet reduces
hypoglycaemia-induced neuronal death in young rats Neurosci Lett
2005 385 210ndash214
17 nehlig a Brain uptake and metabolism of ketone bodies in animal
models Prostaglandins Leukot Essent Fatty Acids 2004 70
265ndash275
18 Hernaacutendez mJ Vannucci RC Salcedo a Brennan RW Cerebral blood
flow and metabolism during hypoglycemia in newborn dogs
J Neurochem 1980 35 622ndash628
19 Vannucci RC nardis ee Vannucci SJ Campbell pa Cerebral
carbohydrate and energy metabolism during hypoglycaemia in
newborn dogs Am J Physiol 1981 256 H1659ndashH1666
20 anwar m Vannucci RC autoradiographic determination of regional
cerebral blood flow during hypoglycaemia in newborn dogs Pediatr
Res 1988 24 41ndash45
21 Hawdon Jm Williams aF et al Formula supplements given to
healthy breastfed preterm babies inhibit postnatal metabolic
adaptation results of a randomised controlled trial Arch Dis Child
2000 82 a30
paeDiatRiCS anD CHilD HealtH 184 16
22 de Rooy l Hawdon Jm nutritional factors that affect the postnatal
metabolic adaptation of full-term small- and large-for gestational
age infants Pediatrics 2002 109 e42
23 Hawdon Jm Hypoglycaemia and brain injury ndash when neonatal
metabolic adaptation fails in levene m ed Fetal and neonatal
neurology and neurosurgery edinburgh Churchill livingstone in
press
24 Hussain K Congenital hyperinsulinism Semin Fetal Neonatal Med
2005 10 369ndash376
25 acolet D Diabetes in pregnancy Caring for the Baby after Birth
CemaCH 2007 2
26 Hussain K Sharief n the inaccuracy of venous and capillary blood
glucose measurement using reagent strips in the newborn period
and the effect of haematocrit Early Hum Dev 2000 57 111ndash121
27 Hawdon Jm Disorders of blood glucose homeostasis in the neonate
in Rennie Jm ed Robertonrsquos textbook of neonatology 4th edn
edinburgh Churchill livingstone 2005
28 Deshpande S Ward platt mp the investigation and management
of neonatal hypoglycaemia Semin Fetal Neonatal Med 2005 10
351ndash361
Practice points
bull identify risk factors for impaired metabolic adaptation
bull Clinical monitoring including accurate blood glucose
measurement for at-risk babies
bull Feed at-risk babies soon after birth and maintain thermal
homeostasis
bull take first blood glucose level at 3ndash4 h of age
bull intervene in at-risk baby with no clinical signs if two
consecutive blood glucose measurements lt 20 mmollitre
bull intervene in any baby with blood glucose measurement
lt 10 mmollitre
bull intervene in any baby with abnormal clinical signs regardless
of blood glucose level
bull investigate for underlying cause of failure of metabolic
adaptation
bull maintain lactation and breast feeding
5 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Resuscitation of the term and premature babyJonathan Wyllie
Abstractalthough most newly born babies establish normal respiration and
circulation without help up to 1minus2 may require some resuscitation
or stabilization Babies who do not establish adequate regular normal
breathing or who have a heart rate of less than 100 beatsmin or other
problems such as prematurity may require assistance the differences in
approach to the resuscitation of such babies originate in the physiology
and pathophysiology of acute asphyxia at birth However management
of airway and breathing remain the key features of resuscitation and
where cardiac depression has occurred this is nearly always due to hy-
poxia secondary to respiratory compromise therefore most babies will
respond within 2minus3 min of effective aeration of the lungs and the need
for intubation chest compressions or drugs is rare the international
liaison Committee on Resuscitation (ilCoR) evaluated evidence in 2000
and 2005 in order to provide guidelines for resuscitation they will do
so again for 2010 this evidence is limited in terms of both quantity and
quality and controversies still exist more research is needed to ensure
that our future actions are based upon evidence rather than history this
article will review the recommended approach to resuscitation as well as
some newer evidence
Keywords guidelines neonatal newborn premature resuscitation
Background
In the UK 669 601 babies were born alive in 2006 and most made the transition to extrauterine life without problems Those babies who did not establish adequate regular normal breathing or who had a heart rate of less than 100 beatsmin may have required assistance1 Factual evidence concerning the true requirement for resuscitation at birth is sparse Up to 10 of newborns may require some assistance to begin breathing with less than 1 needing extensive resuscitation2 However just because a baby received resuscitation does not necessarily mean that it was required and rates of intervention may be altered by educa-tion34 or the personnel present at deliveries5 In a UK tertiary centre with a standard approach to resuscitation at birth up to 12 of all babies received some airway assistance with just over 1 being intubated3 In Sweden only 1 of babies over 2500 g required mask or endotracheal tube ventilation at birth of which most responded to the former4
Jonathan Wyllie MBChB FRCPCH is Consultant Neonatologist at the James
Cook University Hospital Marton Road Middlesbrough TS4 3BW UK
paeDiatRiCS anD CHilD HealtH 184 16
Sometimes it is possible to predict babies who are likely to have respiratory depression at birth and to have appropriate per-sonnel present at delivery Guidelines for attendance at deliveries will vary with institution but even when almost 40 of deliv-eries are attended there may still be a further 15 of babies who require unexpected resuscitation5 a proportion that seems to remain whatever changes are made
The physiology of babies requiring help at birth has been summarized previously167 It allows a logical approach to resus-citation (Figure 1) when evidence is lacking and may prompt further research
Resuscitation at birth
PreparationAt birth resuscitation is more likely in babies with intrapartum evidence of significant fetal compromise those less than 35 weeksrsquo gestation those delivering vaginally by the breech and in multiple births Personnel trained in newborn resuscitation should be available at every delivery1 Someone experienced in tracheal intubation and advanced resuscitation should also be easily available for normal low-risk deliveries in hospital and ideally in attendance for deliveries with an increased likelihood of needing resuscitation In the latter cases the equipment and environment can be prepared beforehand including a discussion with the parents Wash your hands put on gloves and consider what help may be needed
Cord clampingAt birth it has long been known that delay in clamping the cord will lead to less anaemia in babies and reduce subsequent iron deficiency8 However few hospitals have practised this interven-tion due to worries about hypothermia and the need to resusci-tate or stabilize babies In developed countries the advantages seemed to be outweighed by the potential disadvantages A recent randomized controlled study of delayed clamping of the cord in premature babies found that the intervention group had less late-onset sepsis and fewer intraventricular haemorrhages9 This is a low-risk strategy which needs further evaluation in order to introduce it without increasing other risk factors in pre-mature deliveries
Assessment and temperature controlAssessment and temperature control for the newborn baby should occur at all deliveries The assessment indicates the need for resuscitation Babies may vary from 23 to 40+ weeksrsquo ges-tation and in weight from 500 to 5000 g They are born naked and wet and if left cannot cope with an environmental tem-perature of less than 32degC However if the term baby is imme-diately dried put skin-to-skin with the mother and covered the delivery room temperature can be as low as 25ndash28degC Obviously the smaller the baby the greater the surface area to mass ratio and the greater the risk of hypothermia Compromised babies are particularly vulnerable10 and hypothermia will lower oxygen tension11 increase metabolic acidosis12 and inhibit surfactant production13
An effective method of maintaining the temperature of prema-ture babies less than 28 weeksrsquo gestation is wrapping them with plastic before drying and then placing them under a radiant
6 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Dry the babyRemove any wet towels and cover
Start the clock or note the time
Give 5 inflation breathsLook for a response
If no increase in heart rate look for chest movement
Re-check head positionApply Jaw thrust
Repeat inflation breathsLook for a response
If no increase in heart rate look for chest movement
Try alternative airway opening manoeuvresRepeat inflation breaths
Look for a response
If no increase in heart rate look for chest movement
If the heart rate is not detectable or slow (lt60)Start compressions
3 compressions to each breath
Reassess heart rate every 30 secondsConsider venous access and drugs
Assess colour tone breathing and heart rate
Open the airway
If not breathing
If still not breathing
If no response
If still no response
When the chest is moving
If meconium present
Baby breathing wellDo not suction the airway
Baby floppy and not breathing wellConsider inspection and suction before
inflation breaths
Head in neutral position
Inflation breathsUse a well-fitting face mask
connedted to a
pressure-limited gas supply
Each breath 2ndash3 seconds
duration at 30 cm H2O for a
term baby
Get help from a second personto support the airway andor
inspect the oropharynx under
direct vision and consider
suction andor insert an
oropharyngeal airway
Chest compressionsCompvent ratio 31
Rate 120 events per minute
Ensure the chest moves with each ventilation breath
If breathingReassess heart rate and monitor baby
If heart rate is satisfactory but increasingContinue ventilation breaths at about 30 per
minute until baby is breathing adequately
If heart rate is satisfactory but increasingContinue ventilation breaths at about 30 per
minute until baby is breathing adequately
If heart rate is increasingStop compressions
Continue ventilation breaths at about 30 per
minute until baby is breathing adequately
If the chest is not movingRecheck head position and repeat inflation
breaths If competent consider intubation
If the chest is still not movingThe airway is the problem
Figure 1 newborn life support (Courtesy of the Resuscitation Council uK)
heater14 There is a small risk of hyperthermia so the temperature must be monitored carefully
An assessment is made of the babyrsquos colour tone respira-tions and heart rate127 The most important of these is heart rate and a stethoscope is more reliable than cord pulsation15 How-ever saturation monitors may offer a more reliable assessment of both heart rate and colour16 but their interpretation requires a detailed knowledge of normal saturations at birth at differing gestations A baby who is apnoeic and floppy in the absence of neurological disease is unconscious and likely to be in terminal apnoea however this does not change the initial approach other
paeDiatRiCS anD CHilD HealtH 184 167
than the need to summon help early APGAR scores are never calculated to guide resuscitation
Airway
If a baby is in primary apnoea then with an open airway the first gasp will start to aerate the lungs and most babies will be able to lsquoresuscitatersquo themselves as shown in physiological stud-ies on animals Neutral positioning of the babyrsquos head chin lift jaw thrust oropharyngeal airways and endotracheal intubation may all be helpful in certain situations if performed correctly17
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Endotracheal intubationThe placement of an endotracheal tube has long been the gold standard of airway control and this remains true in the unconscious baby if it is correctly sized placed and fixed in a timely manner However experience is directly related to effec-tiveness in endotracheal intubation1819 and the success rate of less experienced clinicians such as a resident (STA1-3) or a fel-low (STA3-5) is lower varying between 33 and 68 Even senior neonatologists often take longer than guidelines recom-mend19 Experienced clinicians may judge correct endotracheal position visually or by an increase in heart rate with the first breaths but detection of exhaled carbon dioxide will give more rapid confirmation in larger babies12171920 and this can be par-ticularly useful for less experienced clinicians or those supervis-ing them However not all systems for the detection of exhaled carbon dioxide work in the smallest premature infants
Laryngeal masksLaryngeal masks may be effective for ventilating term newborn babies but there are few data for small premature infants There have been reports of dislodged laryngeal airways during paedi-atric arrests when chest compressions have been administered Although success of placement at first attempt by paediatri-cians is greater with a laryngeal mask than with an endotra-cheal tube21 the only and small randomized controlled trial in the delivery room favoured endotracheal intubation when per-formed by an anaesthetist22 Based mainly upon case reports the laryngeal mask can be recommended when positioning and mask ventilation and endotracheal intubation have failed to secure the airway but not as yet as a primary method of airway control
MeconiumIn 2000 Wisewell et al23 reported a large randomized controlled trial showing that tracheal intubation and suctioning of meco-nium-stained but vigorous babies at birth did not reduce the incidence or severity of meconium aspiration syndrome More recently another randomized trial has now shown that suction-ing on the perineum similarly offers no benefit24 Neither of these practices is recommended but intubation and suction of meconium from the trachea of non-vigorous babies born through meconium-stained liquor is still recommended
Breathing
In the apnoeic baby the first breaths establish the resting lung volume and aerate the fluid-filled alveoli This mechanical effect aided by surface tension within the alveoli causes the initial fall in pulmonary vascular resistance Experimentally this effect occurs even if the lungs are ventilated with nitrogen but is increased when air is used presumably due to the vasodilator effect of 21 oxygen The mechanical stretching of the lung also triggers the activation of cyclo-oxygenase beginning the production of prostacyclin Bradykinin is produced which has a further direct vasodilator effect and also possibly via prostacyclin Therefore adequate airway control and passive ventilation is vital not only because babies requiring resuscitation at birth have an almost uniformly respiratory aetiology but also in order to promote post-natal adaptation and reverse any maladaptation
paeDiatRiCS anD CHilD HealtH 184 16
In term babies peak ventilatory pressures of 20ndash30 cmH2O may be required but the minimal pressure needed to achieve an improvement in heart rate should be used or if there is no response chest wall movement Longer breaths at lower pressure may be more effective in displacing alveolar fluid and establish-ing the resting lung volume in lungs with sufficient surfactant and may improve initial oxygenation However premature new-borns are obviously physiologically and anatomically less pre-pared for delivery than infants at term Over-inflation has been implicated in histological lung damage in animal models and high tidal volumes appear to be equally damaging whether given before or immediately after administration of surfactant How-ever the same effect is not seen if these excessive tidal volumes are delivered 15 min after administration of surfactant2526 It is now thought that both excess end expiratory volume and inad-equate end-expiratory volume may cause lung damage2728 In premature infants it would therefore seem sensible to use lower pressures of 20ndash25 cmH2O12 delivered in a controlled way to prevent over-inflation and to apply positive end-expiratory pres-sure (PEEP) to prevent damage from under-inflation PEEP also improves both lung compliance and gas exchange2930 Without PEEP the airways collapse during the expiratory phase in animal models of newborn resuscitation
If animal data can be extrapolated it would also seem appro-priate to give surfactant as soon as possible to premature babies in order to ameliorate damage2526
The majority of newborn infants requiring resuscitation will re-establish regular respiration after administration of a few breaths which may be due to Headrsquos paradoxical reflex by which the inflation triggers an inspiratory effort
VentilationOnce the lungs are aerated if the newborn remains apnoeic ventilation should be continued at 30ndash60 breathsmin avoiding hyperventilation and using the minimum pressure possible to maintain a heart rate greater than 100 beatsmin
Face mask the majority of infants who require ventilation receive it via a face mask This may be attached to a bagvalve system with a spring lsquoblow offrsquo system or a lsquoT-piecersquo with a set flow and pressure It is important to realize that the bagvalve system is flow sensitive and that the harder the operator presses the greater the flow and the higher the delivered pressure In fact 60 cmH2O can be achieved with vigorous squeezing of a self-inflating bag Therefore it may be advantageous that most opera-tors are unlikely to be as effective as they suppose in creating a seal with the mask31 This is a skill that requires tuition and prac-tice31 In delivering a set pressure T-piece systems such as the Tom Thumbcopy or Neopuffcopy perform better than any bagminusvalve system but require a gas supply There is no evidence that lung compliance can be assessed using any bag system
Continuous airway pressure case series have suggested that early or delivery room use of continuous positive airway pres-sure (CPAP) in premature babies may reduce chronic lung dis-ease There have been two randomized trials of which one was a pilot study The data from the COIN trial do not show any advan-tage other than a reduction in intubation and surfactant use in the intervention group However an excess of pneumothorax
8 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
was also reported The Vermont Oxford Network and the SUP-PORT trials will provide further data but at present the delivery room use of CPAP cannot be widely recommended and should be limited to those units experienced in its use or taking part in research
Air or oxygen oxygen has been in widespread use for resuscita-tion at birth since the 1930s and even hyperbaric oxygen was seriously supported in the 1960s For many years there have been concerns about tissue damage from oxygen deprivation during and after resuscitation It became evident in the 1950s that unrestricted oxygen therapy could have serious conse-quences for future vision More recently concerns have been raised about potential adverse effects on respiratory physiology cerebral circulation and tissue damage from oxygen free radicals even during resuscitation A meta-analysis of four human studies demonstrated a reduction in mortality and no evidence of harm in infants resuscitated in air versus 100 oxygen3233 However there are several significant methodological concerns with these studies and the results should be interpreted with caution There is insufficient evidence to recommend any specific concentration of oxygen to be used for newborn resuscitation Monitoring the oxygen saturation of babies may be helpful but as yet there are no time-related normal target ranges and healthy term babies may take up to 10 min to achieve preductal oxygen saturation of greater than 95 and up to 60 min to achieve this postductally
There is therefore equipoise which would be open to an appropriate randomized controlled trial In the meantime the evidence only supports use of either 21 or 100 oxygen It is provoking to realize that if air had been in constant use since the 1930s there would be insufficient evidence for use of supple-mental oxygen
Circulation
Early resuscitation (temperature control airway breathing) provides oxygenated blood in the pulmonary arterioles which if returned to the heart causes the rate to increase34 If due to acidosis and hypoxia the circulation is ineffective then chest compressions may be needed They should be commenced when the heart rate remains below 60min despite effective airway and breathing management127 The best technique is using two hands to encircle the chest1 A ratio of three compressions to one breath is internationally accepted127 but has no evidence to support it Research has shown that neither compressions nor drugs will work in this situation without oxygenated blood so effective lung aeration and ventilation is essential A logical approach would be to fill the alveoli with air and to compress the chest until they are empty However training and teamwork require an agreed ratio which has therefore not changed since guidelines were first agreed internationally Success is assessed by an increase in heart rate which should therefore be assessed every 30 s Compressions stop when the spontaneous heart rate is greater than 60 beatsmin
In hypoxic newborn animal models successful resuscitation can restore cardiac output and blood pressure to levels above baseline within 5ndash10 min However it should be noted that there is a decline to 30 lower than basal levels within 2 h and that blood pressure is relatively spared suggesting an even greater
paeDiatRiCS anD CHilD HealtH 184 16
reduction in tissue perfusion This should be considered in the later care of any neonate who was hypoxic at birth
Drugs
Neonatal bradycardia at birth is almost always due to hypoxia plusmn acidosis and therefore drugs are rarely needed Adrenaline (epi-nephrine) is reported as being used in between 1 and 4 babies per 2000 births which is a large variation in practice Reported success is also variable and must be interpreted in light of this variation The use of drugs in extremely premature infants is con-troversial Some data suggested good outcomes for babies below 28 weeksrsquo gestation given adrenaline but these were flawed by high numbers of babies receiving resuscitative drugs some before the airway had been appropriately managed Audit data now suggest a poor outcome such that many clinicians would now council against the use of adrenaline and other drugs to resuscitate extremely premature newborn babies
Adrenaline (epinephrine)In 2003 a Cochrane review of randomized controlled trials involv-ing adrenaline use for resuscitation of neonates was unable to identify a single clinical trial35 Despite the lack of human neo-natal data animal models show the potential of adrenaline in asphyxial cardiac arrest and it is reasonable to use it when ade-quate ventilation and chest compressions have failed to increase the heart rate above 60 beatsmin Use 10ndash30 μgkg intrave-nously and preferably via an umbilical venous line The tracheal route cannot be recommended but if used it is likely that doses within this range will be ineffective and 100 μgkg might be tried However the safety of such doses has not been studied
BicarbonateThe use of bicarbonate has long been controversial but many of the concerns relate to the rapid correction of acidosis in neonates after resuscitation or the routine use of bicarbonate infusion nei-ther of which can be advocated There are no published human neonatal data to support its use although some exist from animal studies Animal data have also shown that the binding of adren-aline to receptors in the myocardium is significantly impaired by lactic acidosis and recent work on human lymphocyte beta-adrenergic receptors supports this view Whether this is also true of the more important alpha receptors is unknown In practice reversing intracardiac acidosis may improve myocardial function and assist in achieving a return of spontaneous circulation 1ndash2 mmolkg of bicarbonate may be given but this remains a contro-versial area
VolumeVolume expansion should only be given when it is suspected that the baby has suffered blood loss or the infant appears to be in shock (pale poor perfusion weak pulse) and has not responded adequately to other resuscitative measures If there is no history suggestive of blood loss shock is most likely to be due to myo-cardial dysfunction in which case fluids should be administered cautiously The most logical replacement fluid would be blood but in its absence isotonic crystalloid rather than albumin is the solution of choice given in 10 mlkg aliquots and observing the response Three randomized trials in neonates have shown
9 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
isotonic crystalloid to be as effective as albumin for the treat-ment of hypotension but none has examined either the relative or actual effectiveness in resuscitation A recent blinded randomized study comparing normal saline albumin or no volume expansion in a normovolaemic asphyxiated neonatal animal model showed that volume expansion was not beneficial and made a number of parameters worse36
NaloxoneNaloxone is not recommended as part of the initial resuscita-tion of newborns with respiratory depression Before it is given supporting ventilation should have restored the heart rate and colour The dose is 100 μgkg intravenously or intramuscularly Tracheal administration cannot be recommended Although administration of naloxone to neonates who have been exposed to maternal opioids during labour is a practice of long-standing it lacks the proper evidence of efficacy
Non-response to resuscitation
There are few more frightening situations professionally than applying the correct interventions in resuscitating or stabilizing a baby and getting no response Each stage must be adequately performed before moving onto the next and this requires regular reassessment When experienced help is needed at a newborn resuscitation it is usually the airway and ventilation that require correction If the heart rate does not increase this usually means that the lungs have not been successfully aerated In some cases however it may mean that the heart cannot respond as the cir-culation is inadequate In this situation the only way to check that the lungs have been successfully aerated is to see the chest move with ventilation or to obtain evidence of ventilation from a detector of exhaled carbon dioxide If you do not see chest movement after another five breaths the most likely cause is an obstructed airway either due to incorrect positioning or because the jaw has not been drawn forwards An oropharyngeal airway can be very helpful at this point especially in the term baby Only very occasionally is the airway blocked by mucus vernix blood or meconium but if the airway is guaranteed and there is no heart rate response or chest movement this should be sought by direct suction of the trachea even in the absence of any meconium staining of liquor Pneumothoraces can occur spontaneously after delivery but are rare at resuscitation carried out with pressure-limited devices Equally rare are diaphragmatic hernias that have not been diagnosed antenatally giving problems at resuscitation
If the chest is moving but the heart rate has not responded to resuscitation consider rare possibilities such as fetal blood loss pneumothorax or heart block (mothers with undiagnosed systemic lupus erythematosis delivered for fetal bradycardia) as possibilities With adequate ventilation there is no evidence of oxygen concentrations less than 100 being responsible for prolonged bradycardia or failure to respond although current practice would support increasing the delivered oxygen concen-tration if resuscitation had been commenced using air
Outcome
The prognosis for the full-term baby subjected to sudden acute asphyxia is usually good provided the episode does not last for
paeDiatRiCS anD CHilD HealtH 184 17
long Most babies resuscitated from primary apnoea have no sequelae secondary to the resuscitation Many babies who start to breathe again regularly within 20 min of the circulation being restored recover completely but it is rare for a baby who is still gasping after 30 min to recover
The prognosis for the preterm baby of less than about 34 weeksrsquo gestation subjected to severe acute anoxia is less predict-able This is because of the risk of secondary intraventricular haemorrhage or periventricular intracerebral haemorrhage andor infarction after even a relatively brief asphyxial episode espe-cially in the period immediately around birth
The effects of chronic hypoxia are also difficult to predict but a reasonably clear idea of the extent of the problem should be obtainable within 36ndash48 h of the original chronic asphyxial insult A mild short-lasting state of hyperexcitability usually car-ries a good prognosis even if there is seizure activity but more severe symptoms can be associated with permanent handicap This is seen especially in infants with encephalopathy requiring ventilation
REFERENCEs
1 Biarent D Bingham R Richmond S et al european Resuscitation
Council guidelines for Resuscitation 2005 Section 6 paediatric life
support Resuscitation 2005 67(suppl 1) S97ndashS133
2 international liaison Committee on Resuscitation part 7 neonatal
resuscitation Resuscitation 2005 67 293ndash303
3 Singh J Santosh S Wyllie J mellon a effects of a course in
neonatal resuscitation - evaluation of an educational intervention
on the standard of neonatal resuscitation Resuscitation 2006 68
385ndash389
4 palme-Kilander C methods of resuscitation in low-apgar-score
newborn infants - a national survey Acta Paediatr 1992 81
739ndash744
5 Kroll l twohey l Daubeney p et al Risk factors at delivery and
the need for skilled resuscitation Eur J Obstet Gynecol Reprod Biol
1994 44 175ndash177
6 Wyllie Jp Resuscitation of the newborn The Foundation Years
2007 3(4) 153ndash157
7 Richmond S ed newborn life Support Resuscitation at Birth
london Resuscitation Council 2006
8 Ceriani Cernadas Jm Carroli g pelligrine l et al the effect of timing
of cord clamping on neonatal venous hematocrit values and clinical
outcome at term a randomized controlled trial Pediatrics 2006
117 e779ndashe786
9 mercer JS Vohr BR mcgrath mm padbury JF Wallach m oh W
Delayed cord clamping in very preterm infants reduces the incidence
of intraventricular hemorrhage and late-onset sepsis a randomized
controlled trial Pediatrics 2006 117 1235ndash1242
10 Dahm lS James lS newborn temperature and calculated heat loss
in the delivery room Pediatrics 1972 49 504ndash513
11 Stephenson J Du J tk o the effect of cooling on blood gas
tensions in newborn infants J Pediatr 1970 76 848ndash852
12 gandy gm adamsons Jr K Cunningham n Silverman Wa James lS
thermal environment and acid-base homeostasis in human infants
during the first few hours of life J Clin Invest 1964 43 751ndash758
13 gluck l Kulovich mV eidelman ai et al Biochemical development
of surface activity in mammalian lung pulmonary lecithin synthesis
0 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
in the human fetus and newborn and etiology of the respiratory
distress syndrome Pediatr Res 1972 6 81ndash99
14 Vohra S Roberts RS Zhang B Janes m Schmidt B Heat loss
prevention (Help) in the delivery room a randomised controlled
trial of polyethylene occlusive skin wrapping in very preterm infants
J Pediatr 2004 145 750ndash753
15 owen CJ Wyllie Jp Determination of heart rate in babies at birth
Resuscitation 2004 60 213ndash217
16 orsquoDonnell Cp Kamlin Co Davis pg Carlin JB morley CJ Clinical
assessment of infant colour at delivery Arch Dis Child Fetal
Neonatal Ed 2007 92 F465ndashF467
17 international liaison Committee on Resuscitation part 13 neonatal
Resuscitation guidelines Circulation 2005 112(suppl 24)
iV188ndashiV195
18 leone ta Rich W Finer nn neonatal intubation Success of
pediatric trainees J Pediatr 2005 146 638ndash641
19 orsquoDonnell Cp Kamlin Co Davis pg morley CJ endotracheal
intubation attempts during neonatal resuscitation success
rates duration and adverse effects Pediatrics 2006 117
e16ndash21
20 Repetto Je Donohue pa-CpK Baker SF Kelly l nogee lm use of
capnography in the delivery room for assessment of endotracheal
tube placement J Perinatol 2001 21 284ndash287
21 gandini D Brimacombe JR neonatal resuscitation with laryngeal
mask airway in normal and low birth weight infants Anesth Analg
1999 89 642ndash643
22 esmail n Saleh m ali a laryngeal mask airway versus endotracheal
intubation for apgar score improvement in neonatal resuscitation
Egypt J Anesthiol 2002 18 115ndash121
23 Wiswell te gannon Cm Jacob J et al Delivery room management
of the apparently vigorous meconium-stained neonate results of
the multicenter international collaborative trial Pediatrics 2000
105 1ndash7
24 Vain ne Szyld eg prudent lm Wisewell te aguilar am Vivas ni
oropharyngeal and nasopharyngeal suctioning of meconium-stained
neonates before delivery of their shoulders multicentre randomised
controlled trial Lancet 2004 364 597ndash602
25 Bjorklund lJ ingimarsson J Curstedt t larsson a Robertson B
Werner o lung recruitment at birth does not improve lung function
in immature lambs receiving surfactant Acta Anaes Scand 2001 45
986ndash993
26 Bjorklund lJ ingimarsson J Curstedt t et al manual ventilation
with a few large breaths at birth compromises the therapeutic effect
of subsequent surfactant replacement in immature lambs Pediatr
Res 1997 42 348ndash355
paeDiatRiCS anD CHilD HealtH 184 17
27 taskar V John J evander e Robertson B Jonson B Surfactant
dysfunction makes lungs vulnerable to repetitive collapse and re-
expansion Am J Respir Crit Care Med 1997 155 313ndash320
28 muscedere Jg mullen JB gan K Slutsky aS tidal ventilation at low
airway pressures can augment lung injury Am J Respir Crit Care Med
1994 149 1327ndash1334
29 nilsson R grossman g Robertson B Bronchiolar epithelial lesions
induced in the premature rabbit neonate by short periods of artificial
ventilation Acta Pathol Microbiol Scand 1980 88 359ndash367
30 probyn me Hooper SB Dargaville pa et al positive end expiratory
pressure during resuscitation of premature lambs rapidly improves
blood gases without adversely affecting arterial pressure Pediatr
Res 2004 56 198ndash204
31 Wood Fe morley CJ Dawson Ja et al improved techniques
reduce face mask leak during simulated neonatal resuscitation
study 2 Arch Dis Child Fetal Neonatal Ed in press doi101136
adc2007117788
32 tan a Schulz a orsquoDonnell CpF Davis pg air versus oxygen for
resuscitation of infants at birth Cochrane Database Syst Rev 2004
(3) CD002273
33 Davis pg tan a orsquoDonnell Cp Schulze a Resuscitation of newborn
infants with 100 oxygen or air a systematic review and meta-
analysis Lancet 2004 364 1329ndash1333
34 Dawes g Fetal and neonatal physiology Chicago year Book
publisher 1968 p 141ndash159
35 Ziino aJa Davies mW Davis pg epinephrine for the resuscitation
of apparently stillborn or extremely bradycardic newborn infants
Cochrane Database Syst Rev 2003 (2) CD003849
36 Wyckoff m garcia D margraf l perlman J laptook a Randomized
trial of volume infusion during resuscitation of asphyxiated neonatal
piglets Pediatr Res 2007 61 415ndash420
Practice points
bull Resuscitation at birth is different from that at all other times
of life
bull a standard approach can be applied to most newborn
resuscitation
bull guidelines are based on a rigorous evaluation of evidence
where possible
bull evidence is sparse but evolving
bull most preterm babies require stabilization rather than
resuscitation
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Acidndashbase physiology and blood gas interpretation in the neonateSusern tan
morag Campbell
Abstractacidndashbase balance describes the complex processes that work to main-
tain a stable extracellular pH for optimal cellular function the process
of balancing the production and neutralization of tissue acid provides a
great challenge for newborn infants who have significantly higher rates
of acid production than adults Factors which help maintain a stable
acidndashbase balance include buffers the respiratory system and renal sys-
tem Both intracellular and extracellular buffers resist changes in pH
the most important extracellular buffer system for maintaining stable
pH is the bicarbonate system in response to acidosis or alkalosis the
respiratory system balances the production of acid with the clearance
of Co2 by altering respiratory rate the kidneys provide a delayed but
sustained response to pH imbalance by excreting either acidic or alkaline
urine in response to systemic acidosis and alkalosis respectively in sick
premature infants these systems have a limited capacity completely to
control pH this review discusses the physiology of the three systems
which control acidndashbase balance patterns of clinical abnormalities in
acidndashbase status and their underlying causes are discussed We present
a systematic approach to blood gas analysis and interpretation in new-
born infants
Keywords acidosis alkalosis bicarbonate bloodndashgas analysis
metabolic pH
Introduction
Blood gas analysis is a routine procedure performed on newborn babies receiving respiratory support in the neonatal intensive care The combination of invasive and non-invasive assessment of ventilation and oxygenation enables clinicians appropriately to modify respiratory care according to each individual babyrsquos rapidly changing clinical status
Understanding the fundamentals of acidndashbase balance helps us to use blood gas analysis not only to assess respiratory sta-tus but also to provide information on metabolic status and the adequacy of tissue perfusion
Susern Tan MBBS MRCP is Clinical Fellow at the Neonatal Intensive Care
Unit 6th Floor North Wing St Thomasrsquo Hospital London SE1 7EH UK
Morag Campbell MBChB MRCP is Consultant Neonatologist at the
Neonatal Intensive Care Unit 6th Floor North Wing St Thomasrsquo
Hospital London SE1 7EH UK
paeDiatRiCS anD CHilD HealtH 184 17
What is understood by acid-base balance
Acidndashbase balance refers to the complex physiological processes used by the body to maintain a stable extracellular pH1 A serum pH within the range of 735ndash745 provides the ideal environment for cellular metabolism Maintaining a stable pH is critical as the metabolic activity of proteins is pH dependent and small changes in hydrogen ion (H+) concentration can potentially alter physio-logical function
Acids are substances that yield free H+ in solution while a base accepts H+ and in solution combines with an acid to neu-tralize it In the normal metabolic state H+ are continuously pro-duced and neutralized to maintain a steady pH balance12 The rate of H+ production is two to three times higher in neonates because of their rapid growth rates and increased acid production from protein turnover and bone mineralization The challenge of maintaining a stable pH through processing and neutralizing H+ is therefore greatest in newborn infants
Using exact values of H+ concentration to assess acidndashbase status is cumbersome and it is more commonly expressed as pH defined by the equation
pH = minuslog H+
Maintaining acidndashbase balance
The balance between production and excretion of acids in the body is controlled by buffer systems which have an immediate effect and by the respiratory and the renal systems
Buffer systemsBuffer solutions resist change in pH when acid or alkali is added due to their capacity to absorb or give up H+ The three main buffer systems in the body are the bicarbonate phosphate and protein systems1ndash3 The protein and phosphate buffer systems are intracellular and act as lsquosinksrsquo for extracellular H+ which are exchanged with intracellular potassium (K+) and sodium ions (Na+) In an acute metabolic acidosis hyperkalaemia may develop due to this H+ exchange4
The bicarbonate buffer system is extracellular and consists of a mixture of carbonic acid (H2CO3) and sodium bicarbon-ate (NaHCO3) This buffer system helps maintain a stable pH by soaking up excess H+ with HCO3
minus which in solution forms carbonic acid (H2CO3) Carbonic acid is a weak acid and readily dissociates to give CO2 which is transported in dissolved form to the lungs for excretion
H+ + HCO3minus harr H2CO3 harr H2O + CO2
The bicarbonate system therefore completes the neutraliza-tion of excess H+ and a stable plasma pH is maintained The relationships between pH HCO3
minus and CO2 in this system are described by the HendersonndashHasselbalch equation15
pH = 61 + log HCO3minus003 times CO2
where 61 is the log of the dissociation coefficient of carbonic acid and 003 the solubility of CO2 in plasma Buffers are most potent when there are equal amounts of H+ and HCO3
minus in solution The
2 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
bicarbonate system is not a potent buffer however as HCO3minus
and CO2 are readily altered by the body this system plays a very powerful role in pH homeostasis15
Respiratory regulationThe respiratory system adapts within minutes to hours as part of the acute response to acidosis This system modifies pH by balancing production of H+ with ventilatory clearance of CO2
H+ directly stimulates chemoreceptors in the respiratory cen-tre of the brainstem producing an increase in respiratory rate26 The response to respiratory acidosis is very rapid as CO2 easily diffuses across the bloodndashbrain barrier however in metabolic acidosis compensation is delayed until plasma bicarbonate fully equilibrates with cerebrospinal fluid (CSF) bicarbonate There is an inverse relationship between alveolar ventilation and partial pressure of dissolved carbon dioxide (PaCO2) a reduction in alveolar ventilation raises PaCO2 and decreases pH Changes in pH therefore affect alveolar ventilation and conversely changes in alveolar ventilation cause significant changes in pH
Renal regulationThe kidneys provide a delayed but sustained response to acidndashbase imbalances by excreting either acidic or alkaline urine In full-term and preterm babies the capacity for acid excretion and bicarbonate reabsorption is reduced as glomerular filtration rates are low and tubular function immature7 Renal function matures with gestation postnatal age and glucocorticoid and thyroid hormones78 Due to their limited capacity to preserve HCO3
minus newborn infants have lower serum bicarbonate levels and are predisposed to acidosis7
Bicarbonate is not effectively reabsorbed due to its size and electrical charge Instead intraluminal HCO3
minus combines with secreted H+ in tubular luminal fluid to produce carbonic acid which dissociates to give H2O and CO2 This CO2 diffuses into tubular cells combines with intracellular H2O and forms carbonic acid which liberates HCO3
minus and H+ HCO3minus is then
recovered to the circulation by exchange for chloride ions (Clminus) through the basal cell membrane247
Renal acid secretion occurs at all sites except the loop of Henle Primary active transport accounts for 5 and secondary for the remaining 95 of total H+ excretion Secondary trans-port involves an exchange between luminal Na+ and intracel-lular H+ Both ions bind to a membrane transport protein The Na+ concentration gradient between the tubular lumen and cells enables Na+ drag into the cell which generates energy to fuel active H+ excretion into the tubular lumen1ndash47
Quantifying acidosis
Standard base excess is a calculated value derived from PaCO2 and pH It is expressed as the mmollitre of base above or below normal buffer bases required to correct the pH to 74 at a PaCO2 of 40 mmHg A negative base excess or base deficit indicates an acidosis while a positive base excess indicates a relative alkalosis15
Anion gap is the measured difference between anions and cations in the blood
Anion gap = (Na+ + k+) minus (HCO3+Clminus)
paeDiatRiCS anD CHilD HealtH 184 17
Calculation of the anion gap enables clinicians better to define the underlying cause of a metabolic acidosis9 The common causes of an increased anion gap acidosis in neonates include lactic acidosis due to tissue hypoperfusion and hypoxia it may also be seen with certain inborn errors of metabolism and in uraemia910 The anion gap can help distinguish between the rela-tively benign non-anion gap hyperchloraemic acidosis seen in premature infants and a pathological lactic acidosis due to poor end-organ perfusion1011
Strong ion theory
Stewart described a complex acidndashbase model which proposed that H+ concentration results from the dissociation of water which is influenced by PaCO2 the strong ion difference and plasma weak acids12
Strong ions are ions that dissociate at normal body pH and include Na+ K+ and Clminus Weak acids in plasma which contrib-ute include albumin inorganic phosphate and plasma proteins their concentrations do not change with pH and are therefore a constant The effect of these factors and other unmeasured tissue ions on acidndashbase status can be quantified by the calculation of the strong ion gap (SIG)112 In the neonatal unit it is perhaps more important that we consider how principles of this model may relate to acidndashbase status rather than fully to quantify the SIG Theoretically low albumin and phosphate levels which fre-quently occur in premature infants by reducing the concentra-tion of weak acids can produce a relative alkalosis while high phosphate levels in renal failure may contribute to acidosis
Tissue oxygenation
Oxygenation is closely linked to acidndashbase status as optimal cel-lular function requires oxygen to fuel aerobic metabolism and produce energy In hypoxic conditions anaerobic metabolism predominates which is energy inefficient and results in a lactic acidosis1011
Tissue oxygen availability is related to regional blood flow haemoglobin level and haemoglobin oxygen affinity Arterial blood gases measure the partial pressure of dissolved oxygen (PaO2) which represents a small component of total oxygen con-tent the majority being transported bound to haemoglobin The relationship between percentage haemoglobin saturation (SaO2) and PaO2 is described by the sigmoidal oxyhaemoglobin disso-ciation curve which enables us to relate the two measures to each other235 The affinity of haemoglobin for oxygen is altered by local tissue factors Increases in temperature H+ PaCO2 and 23-diphosphoglycerate (DPG) levels shift the oxyhaemoglobin dissociation curve to the right reducing affinity for oxygen Decreases in temperature H+ PaCO2 and 23-DPG levels shift the curve to the left increasing oxygen affinity1ndash35 In the body haemoglobin oxygen affinity continuously changes increasing in the lungs to enable efficient oxygen uptake and decreasing at tissue level to provide efficient oxygen delivery to metabolically active tissues
Avoiding both hypoxia and hyperoxia is important in the neo-natal unit as deleterious effects of hypoxia are seen in infants with pulmonary hypertension1314 while hyperoxia is associated with an increased incidence of retinopathy of prematurity1516
3 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Clinical acidndashbase imbalances
Clinical acidndashbase imbalances can be respiratory metabolic or a mixture of both These abnormalities may be corrected by the acidndashbase regulatory mechanisms in the body in an attempt to maintain normal pH (Figure 1)
Respiratory acidosisThis occurs when any disorder leads to decreased alveolar ventilation Common causes of respiratory acidosis are listed in Table 1 Reduced respiratory clearance of CO2 means more dissolved CO2 accumulates in the plasma leading to increased production of carbonic acid and H+ Through chemoreceptor stimulation respiratory acidosis rapidly alters ventilation in an attempt to reduce CO226 Chemoreceptor mediated ventila-tory increases may only partly adjust in premature infants with underlying lung disease In babies with a sustained respiratory acidosis eg in chronic lung disease then metabolic compen-sation occurs through increased renal excretion of H+ and reabsorption of HCO3
minus slowly restoring pH to around 80 of normal47
paeDiatRiCS anD CHilD HealtH 184 17
The management of PaCO2 levels in infants receiving mechan-ical ventilation has important clinical implications Premature babies have impaired cerebral autoregulation17 and adverse neurological sequelae are reported in association with high PaCO2 levels18ndash20 Ventilation strategies which advocate lsquoper-missive hypercarbiarsquo have been developed to minimize airways damage from mechanical ventilation21 Published data suggest pulmonary benefits however the safe level of PaCO2 remains to be defined in premature infants2021
Respiratory alkalosisThis occurs when more CO2 is excreted than is produced by the body Pathological conditions leading to respiratory alkalosis are rare Hyperventilation in the neonatal setting is often iatrogenic or may be due to disorders in brainstem control of breathing including hypoxicndashischaemic encephalopathy or primary central nervous system abnormalities (see Table 1)
If respiratory alkalosis is sustained it may be compensated for by reduced reabsorption of filtered bicarbonate Reported adverse associations of low PaCO2 include periventricular leuco-malacia and intraventricular haemorrhage1922
K+
H+
Overventilation
CO2 + H2O harr H2CO3 harr H+ + HCO3ndash
Bicarbonate Buffer
Intracellular Buffer
uarr H+ excretionuarr HCO3
ndash absorption
uarr buffered H+
(NH4+ H2PO4
ndash)uarr ventilation rate
RespiratoryAcidosis
MetabolicAcidosis
darr CO2and uarr pH
RespiratoryAlkalosis
MetabolicAlkalosis
darr H+ anduarr pH
darr ventilation rate
uarrCO2
and darr pH
darr H+ excretiondarr HCO3
ndash absorption
uarrH+ and
darr pH
Brain
Brain
Intracellular Buffer
H+
K+
Sepsis
HypoxiaRDS
Metabolismand growth
Diuretics
Airwayobstruction
Neuromuscularproblems
IEM
Gastric losses
+ +
ndash -
Renal BufferRespiratory Buffer
Figure 1 mechanisms for regulation of extracellular pH iem inborn errors of metabolism RDS respiratory distress syndrome
4 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Common causes of acidndashbase imbalances
pH PCO2 H2CO3 Base excess Common neonatal causes
Respiratory acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
uarr normal normal bull upper airway obstruction choanal atresia
pierre-Robin sequence
bull lung abnormalities respiratory distress
syndrome transient tachypneoa of
newborn pneumonia meconium aspiration
syndrome pulmonary hypoplasia
congenital pulmonary malformations
bull Central hypoventilation hypoxic-ischaemic
encephalopathy intracranial haemorrhage
bull neuromuscular insufficiency congenital
myopathies congenital neuropathies
bull iatrogenic inadequate ventilatory settings
Compensated lower limit
of normal
uarr uarr gt+3
metabolic acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
normal darr ltminus3 increased anion gap
bull lactic acidosis sepsis hypoperfusion
shock necrotizing enterocolitis
bull inorganic acidosis inborn errors of
metabolism renal failure
normal anion gap
bull increased gastrointestinal H2Co3 losses
ileostomy diarrhoea
bull Renal tubular acidoses
Compensated lower limit
of normal
darr darr ltminus3
Respiratory alkalosis Uncompensated gt 745 darr normal normal bull iatrogenic excessive ventilatory settings
bull Compensatory hyperventilation hypoxic-
ischaemic encephalopathy
Compensated higher limit
of normal
darr darr ltminus3
metabolic alkalosis Uncompensated gt 745 normal uarr gt+3 bull gastric losses vomiting non-replacement
of excessive nasogastric aspirates
bull thiazide and loop diuretics
bull Hypokalaemia
Compensated higher limit
of normal
uarr uarr gt+3
Table 1
Metabolic acidosisThis frequently affects infants in the neonatal unit and has many causes1011 (see Table 1) There may be overproduction of tissue acid impaired acid clearance gastrointestinal loss of bicarbonate or an exogenous increased acid load eg chloride total paren-teral nutrition (TPN) or albumin1ndash323
Calculation of the anion gap to distinguish an increased anion gap acidosis from a non-anion gap acidosis is important both for treatment and prognosis1011 Acidosis stimulates respiratory compensation but this is limited in unstable infants Similarly renal compensation with improved HCO3
minus conservation is con-strained by tubular immaturity Treatment of the acidosis should be directed at the underlying cause eg hypoxia hypotension or excess Clminus rather than by administration of base
Metabolic alkalosisThis is unusual in neonates and is most frequently seen in infants with chronic lung disease or heart failure who are receiving diuretics Diuretics cause alkalosis by increasing renal fluid and Na+ losses An active process to reabsorb Na+ occurs in tubule cells which through enhanced H+ secretion and HCO3
minus reab-sorption produce alkalosis27
paeDiatRiCS anD CHilD HealtH 184 17
Metabolic alkalosis may also occur with excessive loss of gas-tric contents eg protracted vomiting or inadequate replacement of nasogastric aspirates (see Table 1)
Interpreting blood gases
Blood gas measurements can provide important diagnostic and prognostic information and a systematic approach to blood gas analysis is described in Table 2 The clinical management of infants with abnormal gases requires a good understanding of acidndashbase physiology and tissue oxygenation and an apprecia-tion of factors which may affect the reliability of samples
Arterial blood sampling is the gold standard however indwelling arterial catheters and arterial stab samples are usually restricted to infants who are critically ill or those who require sig-nificant ongoing intervention Gases are most frequently measured in capillary or venous samples which correlate well with arterial samples for PaCO2 pH and base excess in babies and children receiving intensive care These correlations however are not valid in infants with peripheral vasoconstriction and hypotension2324
Non-invasive monitoring techniques may enable us to reduce the frequency of blood gas sampling Transcutaneous monitoring
5 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
A systematic approach to blood gas analysis
1 Collect the relevant information
bull type of gas ndash capillary or arterial
bull Current respiratory support ndash document level
bull transcutaneous Co2 and Sao2 levels
bull Clarify no significant clinical events before sampling
2 pH accept a range between 730 and 745 in newborn
babies this is lower than in older children is there an
alkalosis (pH gt 745) or an acidosis (lt 730)
3 Co2 aim for a range between 45 and 65 kpa a paCo2 level
more than 65 kpa suggests inadequate alveolar ventilation
while less than 45 kpa suggests hyperventilation Correlate
values with non-invasive measures
4 o2 Can only be assessed from arterial gases aim for pao2
between 60 and 80 kpa Correlate results with pulse
oximetry levels
5 HCo3 and base excess normal HCo3 level is between 20 and
24 mmollitre and bases excess +3 to minus3
6 anion gap look at the anion gap and lactate to help identify
the cause of an acidosis normal lactate levels should be less
than 2 mmollitre
7 Respiratory or metabolic compensation look at the pH and
assess whether it is appropriate for the Co2 level or is there
evidence of compensation
8 interpret use both the clinical history and blood gas
findings to help you identify the primary problem aim your
management at treating the underlying cause
9 Reassess if clinical management changes have been made
repeat the blood gas after an appropriate time interval to
ensure improvement
Table 2
provides a highly accurate and reliable method for measuring PaCO2 through the skin it can however be technically difficult may cause tissue damage and is of limited reliability when peripheral perfusion is reduced25 Continuous end-tidal CO2 measurements correlate well with arterial CO2 values in patients with normal ventilation and perfusion however in babies with lung disease alveolar collapse small tidal volumes and rapid respiratory rates can make these measurements unreliable26 Despite its limitations transcutaneous monitoring provides the best method for CO2 trend monitoring in the neonatal intensive care unit (NICU)25
Oxygen saturation levels can be continuously measured non-invasively using pulse oximetry While oximetry is easy to perform and accurate on occasion SaO2 levels obtained may be unreliable when tissue perfusion is poor or with movement artefact SaO2 monitoring is highly sensitive at detecting hypoxia but is limited in detecting hyperoxia as at levels more than 90 small changes in SaO2 may result in unacceptably large increases in PaO227 It is therefore essential that SaO2 alarm limits are set for all neonates receiving respiratory support to detect hypoxia and prevent hyperoxia1627
Continuous non-invasive monitoring provides invaluable information when managing complex infants in the NICU but it does not replace the need for regular blood gas analysis
paeDiatRiCS anD CHilD HealtH 184 17
ReFeRenCeS
1 Kellum Ja Determinants of blood pH in health and disease
Crit Care 2000 4 6ndash14
2 Quigley R Baum m neonatal acid base balance and disturbances
Semin Perinatol 2004 28 97ndash102
3 Brouillette Rt Waxman DH evaluation of the newbornrsquos blood gas
status Clin Chem 1997 43 215ndash221
4 Chan JC acid-base disorders and the kidney Adv Pediatr 1983 30
401ndash471
5 Siggaard-andersen o the pH-log pCo2 blood acidndashbase nomogram
revised Scand J Lab Invest 1962 14 598ndash604
6 Saetta m mortola Jp interaction of hypoxic and hypercapnic stimuli
on breathing pattern in the newborn rat J Appl Physiol 1987 62
506ndash512
7 Baum m Quigley R postnatal renal development in Seldin DW
giebisch g eds the kidney physiology and pathophysiology new
york lippincott Williams and Wilkins 2000 p 703ndash726
8 ortiz la Quan a Weinberg a et al effect of prenatal
dexamethasone on rat renal development Kidney Int 2001 59
1663ndash1669
9 gabow pa Kaehny WD Fennessey pV goodman Si gross pa
Schrier RW Diagnostic importance of an increased serum anion gap
N Engl J Med 1980 303 854ndash858
10 lorenz Jm Kleinman li markarian K oliver m Fernandez J Serum
anion gap in the differential diagnosis of metabolic acidosis in
critically ill newborns J Pediatr 1999 135 751ndash755
11 Deshpande Sa platt mp association between blood lactate and
acid-base status and mortality in ventilated babies Arch Dis Child
1997 76 F15ndash20
12 Stewart pa modern quantitative acid-base chemistry Can J Physiol
Pharmacol 1983 61 1444ndash1461
13 Dakshinamurti S pathophysiologic mechanisms of persistent
pulmonary hypertension of the newborn Pediatr Pulmonol 2005
39 492ndash503
14 mourani pm ivy DD gao D abman SH pulmonary vascular
effects of inhaled nitric oxide and oxygen tension in
bronchopulmonary dysplasia Am J Respir Crit Care Med 2004
170 1006ndash1013
15 Deulofeut R Critz a adams-Chapman i Sola a avoiding hyperoxia
in infants le 1250 g is associated with improved short- and long-
term outcomes J Perinatol 2006 26 700ndash705
16 Chow lC Wright KW Sola a Can changes in clinical practice
decrease the incidence of severe retinopathy of prematurity in very
low birth weight infants Pediatrics 2003 111 339ndash345
17 Boylan gB young K panerai RB Rennie Jm evans DH Dynamic
cerebral autoregulation in sick newborn infants Pediatr Res 2000
48 12ndash17
18 Kaiser JR gauss CH pont mm Williams DK Hypercapnia during
the first 3 days of life is associated with severe intraventricular
hemorrhage in very low birth weight infants J Perinatol 2006 26
279ndash285
19 Fabres J Carlo Wa phillips V Howard g ambalavanan n Both
extremes of arterial carbon dioxide pressure and the magnitude of
fluctuations in arterial carbon dioxide pressure are associated with
severe intraventricular hemorrhage in preterm infants Pediatrics
2007 119 299ndash305
20 thome uH Carroll W Wu tJ et al outcome of extremely preterm
infants randomized at birth to different paCo2 targets during the
first seven days of life Biol Neonate 2006 90 218ndash225
6 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
21 Carlo Wa Stark aR Wright ll et al minimal ventilation to prevent
bronchopulmonary dysplasia in extremely-low-birth-weight infants
J Pediatr 2002 141 370ndash374
22 okumura a Hayakawa F Kato t et al Hypocarbia in preterm
infants with periventricular leukomalacia the relation between
hypocarbia and mechanical ventilation Pediatrics 2001 107
469ndash475
23 peters o Ryan S matthew l Cheng K lunn J Randomised
controlled trial of acetate in preterm neonates receiving parenteral
nutrition Arch Dis Child 1997 77 F12ndash15
24 yildizda D yapiciolu H yilmaz Hl Sertdemir y Correlation of
simultaneously obtained capillary venous and arterial blood gases
of patients in a paediatric intensive care unit Arch Dis Child 2004
89 176ndash180
25 aliwalas ll noble l nesbitt K et al agreement of carbon
dioxide levels measured by arterial transcutaneous and end tidal
methods in preterm infants 28 weeks gestation J Perinatol 2005
25 26ndash29
26 Hagerty JJ Kleinman me Zurakowski D et al accuracy of a new
low-flow sidestream capnography technology in newborns a pilot
study J Perinatol 2002 22 219ndash225
paeDiatRiCS anD CHilD HealtH 184 17
27 poets CF Wilken m Seidenberg J Southall Dp von der Hardt H
Reliability of a pulse oximeter in the detection of hyperoxemia
J Pediatr 1993 122 87ndash90
Practice points
bull a stable extracellular pH is important for optimal cellular
functioning
bull abnormalities in acidndashbase balance are regulated by buffer
systems and the respiratory and renal tract
bull maintaining a stable pH is challenging for newborn babies
due to their high rates of acid production and immature
regulatory mechanisms
bull arterial or capillary blood gases provide an effective way to
monitor acidndashbase balance in newborns
bull Blood gases should be analysed in a structured manner
assessing pH and then respiratory and metabolic components
bull the treatment of acidndashbase abnormalities should be directed
at the underlying problem not merely at correcting pH
7 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Recognition and management of neonatal seizuresmalcolm levene
AbstractSeizures are the most common major manifestation of central nervous
system dysfunction in the newborn there are many causes but perina-
tal asphyxia and haemorrhagicinfarction lesions account for about 75
there is now considerable evidence that frequent but short seizures in
the neonate affect subsequent neurodevelopmental outcome Studies
using eeg or modified continuous tracing of eeg activity (aeeg or CFm)
have shown that there is often electroconvulsive dissociation this re-
fers to poor correlation between electrical seizures and clinical seizures
Commonly used anticonvulsants appear to increase electroconvulsive
dissociation effective management of neonatal seizures has proved very
disappointing and less than 50 of seizures are abolished by first-line
anticonvulsant medication (phenobarbitone or phenytoin) Drugs such
as midazolam and lidocaine may further reduce seizures but require
more evaluation the challenge is to assess new and more effective anti-
convulsants which are themselves associated with little neurotoxicity
Keywords antiepileptic drugs eeg neonatal seizures neurodegeneration
Convulsions are the most common major neurological sign seen in newborn infants and their incidence estimated from large population studies is 26 per 1000 live births1 Premature infants are over four times more likely to have convulsions than full-term infants12 Neonatal status epilepticus (continuous seizure activity lasting 30 min or more) diagnosed clinically is rare and accounts for only 5 of infants with seizures1 although this is now recognized more frequently as the result of continuous EEG monitoring3
Neonatal convulsions are described as presenting in a num-ber of different ways and various seizure types can be seen in the same baby over a number of hours The frequencies of the various patterns of seizure activity are given in Table 1 In very premature babies and to a lesser extent in term infants minor movement abnormalities may be difficult to identify as subtle seizures These include lip smacking tongue thrusting mouth-ing pedalling type movements of the lower limbs or swimming movements of the arms Apnoea can be a common manifesta-tion of subtle seizures The signs can be protean and vary from baby to baby or even in the same baby Virtually any stereotypic
Malcolm Levene MD FMedSc FRCPCH FRCH is Professor and Head of
Department of Paediatrics and Child Health at University of Leeds Leeds
and Honorary Neonatologist at Leeds General Infirmary Leeds UK
paeDiatRiCS anD CHilD HealtH 184 178
movement may be a manifestation of a seizure disorder in the newborn
Aetiology
The more carefully the fitting baby is investigated the more likely it is that a cause for the seizures will be found A number of recent papers have described the aetiology of neonatal con-vulsions after extensive investigations14 Tekgul et al4 recently studied a consecutive group of full-term infants with evidence of neonatal convulsions (recognized both clinically and on EEG) and reported their outcome Table 2 summarizes these data as well as risk of moderate or severe disability for each causative factor Perinatal asphyxia is the commonest cause for convul-sions in term infants with haemorrhagic or ischaemic lesions also being common
Overall the prognosis for the group of term babies with con-vulsions was good 72 had a favourable outcome Where asphyxia (hypoxicndashischaemic insult) is the cause of neonatal convulsions the outcome is poor in 50 The prognosis for neonatal convulsions when they were due to arterial or cere-brovenous infarction or intracranial haemorrhage was generally good Individually inborn errors are a very rare cause of neo-natal convulsions but in view of the treatable nature of some of these it is essential that these be considered and investigated appropriately5
Patterns of seizure activity in the newborn
Movement pattern Frequency ()
Clonic 50
tonic 20
Subtle 10ndash35 depending on maturity
myoclonic 5
Table 1
Cause incidence and outcome of neonatal convulsions in term infants14
Aetiological factor Incidence () Poor outcome ()
asphyxia 38ndash40 50
Cerebral arteriovenous
infarction
20 0
intracranial haemorrhage 12ndash20 13
Congenital cerebral anomaly 5ndash10 100
Hypoglycaemiahypocalcaemia 3ndash19
infection 3ndash20
inborn error of metabolism 1
unknown cause 10ndash13 0
Refers to moderate and severe neurodevelopmental abnormalitynumbers too small to make meaningful predictions
Table 2
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Controversies in the clinical management of neonatal seizures
In recent years we have learnt much more about the neurobi-ology of seizures and their effect on the developing brain The neonatal brain is in a neurophysiologically hyperexcitable state compared to the more mature brain and therefore is more prone to seizure activity This is due largely to a relative excess of GABA neuroreceptors GABA receptors are usually inhibitory but in the immature brain they have a paradoxically excitatory effect This changes at about term in primates and with progressive develop-ment they adopt a neuroinhibitory role6
The propensity to seizures in the neonatal brain makes resolv-ing the balance of risks between continuing seizure activity on the one hand against potentially adverse effects of therapy on the other a very important equation Added to this is the problem of accurately diagnosing neonatal seizures and whether commonly used anticonvulsants are successful in controlling them
These conundrums can be posed as a series of challenging questions which are discussed below
Do neonatal convulsions cause brain injuryConvulsions are a sign of neurological compromise and may indi-cate significant underlying structural brain damage or biochemi-cal disturbance which may cause further brain damage in its own right There has been considerable debate about the scale of the disability that convulsions cause the immature brain over and above that due to the underlying cause Most of our knowledge comes from studies in rodents and these have provided some tentative answers to this question
Seizures in the mature brain lead to neuronal necrosis but studies in very young rat pups whose brain development is somewhat similar to full-term infants have shown that a series of five brief seizures on five successive days does not cause struc-tural neuronal damage but does produce morphological changes in hippocampal neurones and worryingly deficits in the rat learning and visual spatial memory function in adolescent and adult life7 A single prolonged neonatal convulsion in similarly immature rats does not produce any functional effects8 Others have shown that following priming of the neonatal rat brain by short seizures as described above a further insult comprising induction of status epilepticus in the same rats at an older age causes neuronal necrosis9 This has been referred to as the lsquotwo hit hypothesisrsquo10
A more specific question is does seizure activity in an already significantly compromised brain cause additional neuropathol-ogy Wirrell et al11 studied a series of immature rat pups with the induction of an hypoxicndashischaemic (asphyxial) insult fol-lowed by either chemically-induced fits or a control sham pro-cedure In the more severely asphyxiated animals the degree of brain damage was increased significantly in those that had the additional burden of induced seizures
In summary these studies show that the immature brain is more resistant to short frequent post-seizure damage than the mature brain but despite resulting in no loss of neuronal numbers the function of the brain is permanently affected in later life In the asphyxiated brain seizures appear to have an additional adverse effect on brain damage Furthermore the immature brain that has been lsquoprimedrsquo by early seizures is more
paeDiatRiCS anD CHilD HealtH 184 179
vulnerable to status epilepticus later in life It would appear from these data that frequent seizures in the human infant should be stopped and this begs the question as to whether currently used anticonvulsants effectively control neonatal seizures
Can we rely on clinical versus EEG diagnosis of neonatal convulsionsTraditionally the diagnosis of neonatal convulsions has been made by observation and description of the frequency of abnor-mal movements EEG has been technically difficult in the hostile electrical activity of a neonatal intensive care environment and considerable expertise is required for analysis of the trace It is usually not practical to undertake traditional EEG recordings at the time the baby shows abnormal movements More recently various technological developments have allowed more direct investigation of neuronal electrical activity by either video-EEG or compressed recording of the amplitude integrated EEG (aEEG or CFM)
Rennie et al3 at Kingrsquos College Hospital London have under-taken extensive evaluation of video-EEG and have found that this technique detects many convulsions not recognized by a single channel aEEG or CFM trace Of 19 infants with evidence of convulsions on EEG only four were recognized on CFM but this may have been due to the observersrsquo lack of experi-ence with this technique In other centres that have developed appropriate expertise aEEG or CFM has proved more sensitive to the detection of seizures Video-EEG studies have also shown that many movements interpreted by experienced clinicians to be seizures are not associated with abnormal cortical activity Conversely many electrical seizures are not associated with abnormal movements This is referred to as electroconvulsive dissociation
In summary clinical observation alone to detect the fitting baby is unreliable in that it may either over-detect seizure activ-ity which is not present on EEG or under-detect clinical seizures in infants with EEG-proven convulsions The decision as to which babies to treat with antiepileptic drugs therefore becomes somewhat arbitrary
Do anticonvulsants stop neonatal seizuresAlthough neonatal seizures are common there are few random-ized controlled trials assessing the benefits of antiepileptic drugs (AEDs) in the treatment of this condition Phenobarbitone is the most widely used first-line AED and in an Australasian study 95 of neonatologists and paediatric neurologists used this drug as first-line management12 The most commonly used loading dosage is 20 mgkg but regimens of up to 40 mgkg have been recommended (Table 3)13 Four trials have evaluated the effect of phenobarbitone in abolishing neonatal seizures Two of these studies used EEG to monitor response to the drug1415 and one compared phenobarbitone with phenytoin15 In the latter study seizures were completely controlled in only 43 of babies and in the group where phenytoin was the first drug used com-plete seizure control was achieved in 45 This study switched babies from their first AED to the other if complete control was not obtained on EEG monitoring after exposure to first-line therapy In babies who had been given phenobarbitone as first-line therapy seizure control was only achieved in 57 after phenytoin was added In those given phenytoin first complete
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Dosage regimens for first- second- and third-line anticonvulsants in the neonatal period
Loading dose Second loading dose if first
unsuccessfulMaintenance dose
phenobarbitone 20 mgkg by slow iv injection 10 mgkg iv 25ndash5 mgkg od
phenytoin 20 mgkg iv over 20 min not recommended
midazolam 150ndash200 μgkg iv infusion 1 μgkgmin iv infusion increasing to 5 μgkgmin
until favourable response
lidocaine 2 mgkg iv over 10 min 6 mgkgh for 6 h iv then 4 mgkgh for 12 h then
2 mgkgh for 12 h
lorazepam 005ndash01 mgkg by slow iv injection
Diazepam 03ndash04 mgkg iv over 3ndash5 min
lidocaine should not be used if the infant has previously been treated with phenytoin
Table 3
seizure control was achieved with the adding of phenobarbitone in 62
Boylan et al14 assessed the efficacy of phenobarbitone (20ndash40 mgkg iv over 20 min) in 14 babies monitored by video-EEG in only four was there complete abolition of seizures and in the other 10 electroconvulsive seizure activity increased whereas clinical evidence of seizures reduced This has been termed elec-troclinical dissociation and anticonvulsant drug use in the new-born appears to increase this feature They also showed that the babies least likely to respond to the first-line AED are those with the most abnormal background EEG
Two studies have evaluated the use of phenobarbitone in babies who had sustained significant asphyxial insult at birth Hall et al13 compared high-dose phenobarbitone (mean 39 mgkg) versus standard dose (27 mgkg) and reported fewer convul-sions and a significant reduction of severe disability or death in the high dose group (RR 030 CI 010ndash093) A recent study from India16 of babies with hypoxicndashischaemic encephalopathy ran-domized 25 babies to phenobarbitone (20 mgkg loading dose) and compared them with 20 control babies Only 2 of 25 (4) in the phenobarbitone group developed convulsions compared with 8 of 20 (40) in the control group (p = 001) Because of the specific enrolment criteria (asphyxial insult) neither of these studies is strictly comparable to the studies by Painter et al15 and Boylan et al14 whose intention was to assess the efficacy of first-line anticonvulsant therapy on convulsions of any cause diagnosed either clinically or by EEG
Other anticonvulsants used as second- and third-line drugs have been subject to few studies in the newborn Midazolam is administered as a bolus followed by continuous infusion A recent study17 has shown that in 10 of 13 neonates given intravenous midazolam for status epilepticus control of electri-cal seizures was achieved within the first hour of treatment having been previously shown to be refractory to phenobarbi-tone treatment Some of these babies required a second bolus infusion of midazolam to obtain control of all electrographic seizures
In some parts of Europe lidocaine is used as a third-line anti-convulsant Malingre et al18 evaluated 20 infants refractory to
paeDiatRiCS anD CHilD HealtH 184 180
both phenobarbitone and midazolam and who were then given lidocaine by continuous infusion Lidocaine was effective in abolishing electroconvulsive seizures diagnosed by aEEG in 76 of the treatment courses studied No babies developed cardiac arrhythmias a previously reported complication of lidocaine in older patients As a result of pharmacokinetic studies the dosage regimen has been modified (see Table 3)
In summary phenobarbitone is effective in seizure control in less than 50 of babies and even when combined with phe-nytoin the efficacy of these drugs together remains poor More worrying is the observation that phenobarbitone tends to reduce clinically evident seizures thereby giving the clinician a false sense of security whilst having little or no effect on the num-bers of electroconvulsive disorders This has been summarized appropriately as lsquoafter all these years we still love what doesnrsquot workrsquo19 Both midazolam and lidocaine infusions appear to be effective in abolishing severe seizures in some infants resistant to phenobarbitone Lidocaine should not be given to babies previ-ously exposed to phenytoin for fear of a synergistic adverse effect on cardiac rhythm
Do antiepileptic drugs cause brain damageA riskndashbenefit analysis is needed to evaluate the efficacy of anticonvulsants in stopping neonatal seizures which is poor with standard anticonvulsants as discussed above against the risk of administering the anticonvulsant drugs themselves Phenobarbitone has been reported to have adverse effects on the developing brain including inhibition of brain growth20 neuronal toxicity21 and adverse behavioural and cognitive effects into adult life when administered to young animals22 Phenytoin shows unpredictable plasma levels and potential cardiotoxicity
Recent studies have shown an effect of AED exposure on the developing brain by causing neurodegeneration23 Phenytoin administration to immature rat pups at doses which produce serum levels similar to those achieved in human neonates was associated with widespread neuronal death as a result of apop-tosis (programmed cell death) Phenobarbitone had a similar effect when a dosage regimen similar to 40 mgkg was used and
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
this effect was maximal in the more immature brain Diazepam and clonazepam also resulted in a similar effect Midazolam and lidocaine were not tested in this study The combination of phenobarbitone or phenytoin with diazepam had a particularly profound effect on neurodegeneration
In summary recent data suggest that the commonly used AEDs for neonatal convulsions may in themselves cause neuro-degeneration due to apoptosis with lasting effects on develop-ment Many babies with neonatal convulsions are treated with at least two AEDs and this may produce more severe adverse effects than the seizures themselves
Practical management of neonatal seizures
Assimilation of these data and formulation of a rational policy is difficult when faced with a fitting neonate on an intensive care unit and pressure on the medical staff to lsquodo somethingrsquo but it is important to accept that sometimes doing nothing is preferable to using potentially dangerous drugs in a situation which does not warrant such intervention Many babies who have normal interseizure neurological clinical findings and whose seizures are relatively brief and infrequent probably do not need anticon-vulsant medication A normal or near-normal background EEG trace should reassure the clinician that anticonvulsants can be withheld
Some causes of neonatal convulsions are treatable such as meningitis hypoglycaemia hypocalcaemia and inborn errors of metabolism and each baby should be rapidly and carefully investigated for cause of the convulsions
In some babies clinical assessment of seizures is difficult ie when the baby is very sick small or paralyzed Sometimes it may be difficult to assess the significance of certain movement pat-terns Under these circumstances an EEG may prove to be very helpful In many units EEG is not available out of hours and a simple aEEG or CFM is strongly advised Modern instruments are very simple to apply and prolonged or frequent seizures should be identified with only moderate training The printout can be faxed to a more senior doctor if there is doubt as to what is shown on the trace
The balance of knowledge now is that frequent seizures cause additional damage to the developing brain and that treatment to abolish the seizures is warranted Unfortunately there is little evidence that the majority of seizures can be effectively termi-nated by current standard therapy Furthermore it appears that the more abnormal the background EEG the more difficult it is to control the seizures Nevertheless a written protocol for the management of neonatal convulsions is required on each unit Phenobarbitone and phenytoin remain the mainstay of treat-ment although their effectiveness is disappointing There is little to suggest that midazolam is more effective than lidocaine as third-line therapy but lidocaine is precluded if phenytoin has been previously used
In view of the anxiety as to the neurodegenerative effects on the immature brain of most anticonvulsants used in the neonatal period (particularly when multiple drugs are used) it is prefer-able to use only one drug to maximum dosage before introduc-ing a second In addition the duration of anticonvulsants should be minimized and the drugs stopped at the earliest opportu-nity It is my practice to stop anticonvulsants prior to discharge
paeDiatRiCS anD CHilD HealtH 184 18
from hospital if the baby is neurologically normal on clinical examination
REFEREnCES
1 Ronen gm penney S andrews W the epidemiology of clinical
neonatal seizures in newfoundland a population-based study
J Pediatr 1999 134 71ndash75
2 lanska mJ lanska DJ Baumann RJ et al a population-based study
of neonatal seizures in Fayette County Kentucky Neurology 1995
45 724ndash732
3 Rennie Jm Chorley g Boylan gB et al non-expert use of the
cerebral function monitor for neonatal seizure detection Arch Dis
Child Fetal Neonatal Ed 2004 89 F37ndashF40
4 tekgul H gauvreau K Soul J et al the current etoliologic profile
and neurodevelopmental outcome of seizures in term newborn
infants Pediatrics 2006 117 1270ndash1280
5 Surtees R Wolf n treatable neonatal epilepsy Arch Dis Child 2007
92 659ndash661
6 Ben-ari y Holmes gl effects of seizures on developmental
processes in the immature brain Lancet Neurol 2006 5 1055ndash
1063
7 Holmes gl gairsa Jl Chevassus-au-louis n et al Consequences of
neonatal seizures in the rat morphological and behavioral effects
Ann Neurol 1998 44 845ndash857
8 Stafstrom Ce Chronopoulos a thurber S et al age-dependent
cognitive and behavioural deficits following kainic-acid inducing
seizures Epilepsia 1993 34 420ndash432
9 Schmid R tandon p Stafstrom Ce et al effects of neonatal seizures
on subsequent seizure-induced brain injury Neurology 1999 53
1754ndash1761
10 Hoffmann aF Zhao Q Holmes gl Cognitive impairment following
status epilepticus and recurrent seizures during early development
support for the ldquotwo-hit hypothesisrdquo Epilepsy Behav 2004 5
873ndash877
11 Wirrell eC armstrong ea osman lD et al prolonged seizures
exacerbate perinatal hypoxic-ischemic brain damage Pediatr Res
2001 50 445ndash454
12 Carmo KB Barr p Drug treatment of neonatal seizures by
neonatologists and paediatric neurologists J Paediatr Child Health
2005 41 313ndash316
13 Hall Rt Hall FK Daily DK High-dose phenobarbital therapy in term
newborn infants with severe perinatal asphyxia a randomized
prospective study with three-year follow-up J Pediatr 1998 132
345ndash348
14 Boylan gB Rennie Jm pressler Rm et al phenobarbitone neonatal
seizures and video-eeg Arch Dis Child Fetal Neonatal Ed 2002 86
F165ndash170
15 painter mJ Scher mS Stein aD et al phenobarbital compared with
phenytoin for the treatment of neonatal seizures N Engl J Med
1999 341 485ndash489
16 Singh D Kumar p narang a a randomized controlled trial of
phenobarbital in neonates with hypoxic ischemic encephalopathy
J Matern Fetal Neonatal Med 2005 18 391ndash395
17 Castro Conde JR Borges H Domenech martinez e et al midazolam
in neonatal seizures with no response to phenobarbital Neurology
2005 64 876ndash879
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
18 malingre mm Van Rooij lgm Rademaker Cma et al Development
of an optimal lidocaine infusion strategy for neonatal seizures Eur
J Pediatr 2006 165 598ndash604
19 Sankar R painter mJ neonatal seizures after all these years we still
love what doesnrsquot work Neurology 2005 64 776ndash777
20 Diaz J Schain J Bailey Bg phenobarbital-induced brain growth
retardation in artificially reared rat pups Biol Neonate 1977 32 77ndash82
21 mattson RH phenobarbital toxicity in levy RH Dreifuss Fe
mattson RH et al eds antiepipeptic Drugs 3rd edn new york
Raven 1985 p 341ndash355
22 mikati ma Holmes gl Chronopoulos a et al phenobarbital
modifies seizure-related brain injury in the developing brain Ann
Neurol 1994 36 425ndash453
23 Bittigau p Sifringer m genz K et al antiepileptic drugs and
apoptotic neurodegeneration in the developing brain Proc Natl
Acad Sci U S A 2002 99 15089ndash15094
paeDiatRiCS anD CHilD HealtH 184 182
Practice points
bull the clinician needs to be aware that almost any repetitive
stereotype movement pattern can be a manifestation of
neonatal seizures
bull eeg is important in defining neonatal seizures
bull Frequent short-lived seizures have been shown to cause long-
term neurodevelopmental problems
bull Conventional anticonvulsant medication is ineffective in
abolishing neonatal seizures in greater than 50 of cases
bull there is evidence that exposure of the neonatal brain to
multiple anticonvulsants causes neuronal death
bull Future research is needed to evaluate more effective
anticonvulsants for treating this condition
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
Emotional support for families of sick neonatesMarina nicolaou
cristine Glazebrook
AbstractParents of sick neonates experience high levels of stress anxiety and
depression Most interventions with families of sick infants have focused
on fostering the motherndashinfant relationship through the provision of
information about infant developmental needs or through increased
motherndashinfant contact Many of these studies have reported improved
maternal well-being though there are some concerns about the scope
and practicality of large-scale interventions The few studies to have
prioritized emotional support for parents of sick neonates have pro-
duced encouraging results even interventions requiring relatively few re-
sources such as telephone support parent-to-parent support and group
support have been associated with reduced psychological morbidity for
parents The needs of parents can change throughout their infantrsquos hos-
pitalization and not all want or benefit from the provision of additional
support Thus neonatal intensive care units should aim to provide a
varied flexible and sustainable programme of support options Further
research should focus on the needs of fathers
Keywords mental health neonatal intensive care parents
The admission of an infant to neonatal care is acknowledged to be a source of considerable distress for families This review aims to explore evidence for the psychological impact on families of having an infant in neonatal intensive care and to identify evi-dence for the effectiveness of interventions to promote parental well-being It will conclude with recommendations for strategies to support parents of vulnerable infants and suggestions for fur-ther research
Psychological impact of neonatal care for parents
The majority of research examining the effect on parents of having a sick neonate has focused on families of premature or low birthweight infants Such research has found that parents with a sick neonate exhibit high levels of stress compared to normative samples and to parents of healthy full-term infants1 Singer et al2 examined the stress experienced by mothers of high-risk very low birthweight (VLBW) low-risk VLBW and term
Marina Nicolaou MPhil is a Teaching Assistant at the School of
Community Health Sciences University of Nottingham Nottingham UK
Cristine Glazebrook PhD is a Professor of Health Psychology at the School
of Community Health Sciences University of Nottingham Nottingham UK
PaeDiaTrics anD cHilD HealTH 184 196
infants Several self-report measures were used including the Brief Symptom Inventory the Parenting Stress Index (PSI) the Impact on Family Scale and the Family Inventory of Life Events and Changes (FILE) Mothers of VLBW infants had more psycho-logical distress at 1 month compared to mothers of term infants Mothers of high-risk VLBW infants also reported high psycho-logical distress at 2 years and high levels of parenting stress at 3 years Mothers have also been found to have higher stress levels compared to fathers Shaw et al3 examined the prevalence of acute stress disorder (ASD) in 40 parents whose infants were in the neonatal intensive care unit (NICU) Nearly half of the moth-ers (44) met the criteria for ASD although none of the fathers did Furthermore the severity of the symptoms (measured by the number of concurrent symptoms) was greater for the moth-ers than for the fathers3 The reasons behind this difference have been widely speculated with some believing that it is due to the mothersrsquo greater psychological involvement with the infant as evidenced by their general greater vulnerability to postpartum psychological disorder It could also reflect gender differences in coping style
Having an infant who requires intensive medical care repre-sents a significant emotional burden for families Not only is there extreme anxiety surrounding the infantrsquos health and distress for the childrsquos suffering there is also the unfamiliar and intimidating environment of the NICU to adjust to Hopper in her review of the literature identified sources of stress for parents of sick neo-nates as falling into three areas4 Situational factors included the severity of the infantrsquos illness and how parents adapted to the life crisis of having a sick infant Personal factors involved parental emotions about their roles and the instrumental and informa-tional support which were available to them The third area was classified as environmental sources of stress and included the environment of the NICU and the relationship between parents and members of staff This relationship has been examined by several studies in the nursing literature nurses are seen as ide-ally placed to provide the necessary support and information to parents with sick neonates However whilst some studies have shown that supportive and helpful hospital staff can have a posi-tive effect on parents other studies have highlighted the prob-lems and difficulties which can manifest It has been shown that parents and nurses often have very different ideas about issues eg the necessary skills and competencies needed in an NICU or the characteristics that make a lsquogood motherrsquo
Research has shown that there may be a relationship between high levels of parental stress and an increased likelihood of depression5 Postpartum depression is a psychiatric illness which appears in 10ndash15 of postpartum women Its reported preva-lence rates however have ranged from less than 10 up to 306 depending on the instruments used the population exam-ined and the timing of the research Several factors have been found to be associated with postpartum depression including poor social support and infant-related stressors6 Evidence indi-cates that postnatal depression may be underreported and this is of concern since the mental and psychological health of the mother can affect her relationship with her infant and thus the infantrsquos cognitive and emotional development5 Depressed moth-ers appear to look touch and talk to their infants less frequently and also appear to show fewer positive and more negative faces7 The vocalizations of mothers suffering with depression have also
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
been found to be less effective at promoting cognitive growth and learning in infants8
If researchers are interested in finding ways of providing sup-port for families of sick neonates then they must listen to what such families perceive their needs to be in order to avoid increas-ing anxiety and distress Furthermore the provision of appropri-ate support be it emotional informational or social will enhance parental coping abilities increase self-esteem and reduce anxiety It should be noted though that the research conducted around these issues has often taken lsquosupport needsrsquo as being synony-mous with lsquoinformation needsrsquo Such studies have examined the type the amount and quality of information that parents receive and perceive themselves as needing but have not explored in equal depth the perceived emotional support needs of families who have a sick infant In addition the needs of parents may change throughout their infantrsquos illness Ward examined the per-ceived needs of 52 parents of infants in an NICU9 Parents rated the needs of their hospitalized infant as most important along with the need to be reassured Interestingly they ranked their support needs as least important This research was conducted during the first week of the infantsrsquo hospitalization however which would explain the preoccupation of the parents with the infantrsquos health These results demonstrate that if researchers want to find ways of providing emotional support to parents of sick neonates they must be prepared not only to listen to parents but also to be flexible enough to satisfy the parentsrsquo changing needs and expectations
Interventions aimed at supporting parents
Most interventions that been evaluated in controlled studies have focused on supporting the motherndashinfant relationship and provid-ing information on infant development Many of these interven-tions have included the aim of improving the parental emotional state and thus psychological outcomes such as stress or anxi-ety have been assessed However few studies appear to include fathers This means that strategies implemented to provide emo-tional support to families of sick neonates are often derived from interventions tailored for mothers even though fathers may have different emotional needs
A wide range of interventions with mothers and infants has been evaluated in the NICU Increasing motherndashinfant contact through kangaroo care has been found to reduce maternal anxiety1011 and educational programmes delivered to fami-lies in the NICU have also been associated with reduced emo-tional difficulties in parents12ndash14 Kaaresen and colleagues implemented an intervention which consisted of eight sessions before discharge and four home visits all by trained nurses The sample included 71 premature infants in the intervention group 69 premature infants in the control group and 74 infants in the full-term control group The randomized controlled trial found that the intervention reduced parenting stress in both mothers and fathers of premature infants compared to controls to a level equivalent to parents in the term control group13 At 6 months corrected age mothers of preterm infants who had not received the intervention had total PSI scores which were 17 points higher than the mothers of infants born at term (an effect size of 057) A similar study evaluated the efficacy of an educationalndashbehavioural programmendashCreating Opportunities for
PaeDiaTrics anD cHilD HealTH 184 19
Parent Empowerment (COPE) ndash through a randomized controlled trial with 260 families of premature infants14 COPE was a four-phase educationalndashbehavioural programme which began as early as 2ndash4 d after mothers had given birth and continued until 1 week after discharge from the NICU The programme consisted of audiotaped and written infant behaviour information along with photographs which focused on common behaviours and characteristics of premature infants It also included various par-ent activities in the form of a four-phase workbook which aimed to assist mothers in the implementation of the experimental infor-mation COPE was found significantly to reduce maternal stress in the NICU as well as maternal anxiety and depressive symptoms after hospitalization In contrast a cluster randomized trial of a parenting intervention delivered to mothers of very premature infants from soon after birth showed no benefits for parenting stress1 The authors hypothesized that the intervention had not been of sufficient intensity particularly in the weeks surrounding discharge Neonatal care presents a significant barrier to parent-ing in the early weeks following a very preterm birth and so inter-ventions which focus on the developmental needs of infants and the parentndashchild relationship should particularly aim to support parents as they take on the parenting role There was also concern that the intervention had failed to reach those most at risk
Since large-scale projects can be costly to implement and may often fail to reach the families in most need it may be wiser to focus on intervention programmes which are more practical and easier to implement within a neonatal care setting Research has shown that even interventions which are based on one-off meet-ings with parents of sick neonates can be effective Jotzo and Poets examined the effect of an intervention programme aimed at reducing the severity of traumatic responses as a result of giv-ing birth prematurely15 Their programme consisted of a one-off intervention meeting along with additional psychological help throughout the hospitalization of the infant The meeting cov-ered a variety of issues including a reconstruction of the events shortly before and after the infantrsquos birth relaxation techniques discussion of coping strategies available resources and social support and support during emotional outbursts The measures used included the Impact of Event Scale (IES) and the Peritrau-matic Dissociative Experience Questionnaire At discharge the mothers who received the intervention were found to have a significantly lower traumatic impact as a result of premature birth Furthermore fewer mothers in the intervention group showed symptoms of clinically significant psychological trauma at discharge compared to mothers in the control group (36 vs 76)15 The lsquoParents Circle Programrsquo is another intervention with a similar structure16 This consisted of a 90 min session for parents with the aim of enhancing the developing relationship between parents and infants and to offer parents support A total of 104 parents (59 mothers and 45 fathers) and 44 members of hospital staff were asked to evaluate the programme and their results were analysed using content analysis Families reported gaining perspective on their situation feeling supported becom-ing aware of cues and optimizing interactions and becoming aware of available resources Parents and staff alike felt that participating in the intervention helped parents overcome the difficulties associated with the early time of their infantrsquos hos-pitalization Additional studies have also found positive results with fairly minimal interventions including discussion groups
7 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
in the NICU music during kangaroo care and pairing mothers of sick neonates with trained mothers who had been through similar experiences
Parent support programmes
Parent support programmes (PSPs) which are based in NICUs can provide parents with the opportunity to talk to parents who have been in similar situations and also to discuss their emo-tions with professionals who can help them cope with their situa-tion111718 The parent-to-parent support programme for mothers of preterm infants evaluated by Preyde and Ardal included edu-cational parental support group meetings and individual par-ent-to-parent support (primarily telephone support)19 Measures used included the Parental Stressor Scale NICU the State and the Trait Anxiety Inventories and the Beck Depression Inven-tory After 4 months of participation mothers in the intervention group reported lower levels of stress state anxiety and depres-sion compared to control group mothers The authors speculated however that the participants who were able to meet face to face with other parents were those who benefited the most Hurst conducted a comprehensive survey of an NICU-based PSP This PSP was provided in a variety of formats including a weekly parent support group hospital visitation and 24-h telephone sup-port20 Of the 477 participants 303 families used the PSP dur-ing a 2-year evaluation period with 78 using only one form of support and 18 using two forms Of a sub-sample of 48 parents asked to complete an evaluation of the PSP 92 stated that they would recommend such a programme to other parents Furthermore the majority of parents felt that it made them feel supported and helped them deal with their emotions20 This is an indication that such programmes can be very successful in sup-porting parents throughout their infantrsquos hospitalization It also shows that it can be beneficial to give parents several options and formats when it comes to such support services It is impor-tant to consider though that both the Hurst and the Preyde and Ardal studies found that some participants did not find the sup-port programmes helpful even reporting that they had caused them increased stress and anxiety Therefore it should not be assumed that support programmes will suit every individual and will provide the required support for all parents1920 NICUs need to be flexible enough to provide parents with a range of forms of support to choose from
The increased understanding of the strains that parents of sick neonates have to deal with has also led to efforts to improve customary practices in NICUs Family-centred care focuses on infants and their needs and attempts to redefine the relationship between parents and caregivers These practices strive to provide parents with support during their infantrsquos illness by focusing on freely sharing information and on the collaboration between parents and hospital staff Family-centred care has been found to be associated with several beneficial outcomes including improved parental satisfaction increased parental comfort staff satisfaction and decreased parental stress18 Research is already examining these practices and questioning how these can be improved further Such research reflects the increasing effort focused on lsquohumanizingrsquo the environment in NICUs in order to make parents feel more comfortable about spending time with their infants
PaeDiaTrics anD cHilD HealTH 184 19
Conclusion
Surprisingly few interventions have prioritized the provision of emotional support for parents of sick neonates or accounted for the changing needs and wishes of parents over the course of their infantrsquos care Large-scale supportive education-based inter-ventions have been shown to be effective in reducing parental distress However the feasibility and sustainability of such pro-grammes should also be considered Programmes which require significant additional resources can be expensive and there are also issues of training and quality control Interventions which require significant input from parents may also place additional burdens on families making them potentially less accessible to those most at risk Arguably the aim should be to explore ways of providing acceptable and effective informational support which could be complemented by emotional support from health professionals and from other parents in the unit Increasingly studies are exploring the use of computers and multimedia as an engaging flexible and cost-effective method of targeting indi-vidual needs and providing support and information Such com-puter-based and interactive multimedia interventions have been found to be successful with a range of patient groups and could therefore be examined as a complementary method of providing informational support to families with sick neonates
REfEREnCEs
1 Glazebrook c Marlow n israel c et al randomised trial of a
parenting intervention during neonatal intensive care Arch Dis Child
Fetal Neonatal Ed 2007 92 F438ndash443
2 singer lT salvator a Guo s collin M lilien l Baley J Maternal
psychological distress and parenting stress after the birth of a very
low-birth-weight infant JAMA 1999 281 799ndash805
3 shaw rJ Deblois T ikuta l Ginzburg K Fleisher B Koopman c
acute stress disorder among parents of infants in the neonatal
intensive care nursery Psychosomatics 2006 47 206ndash212
4 Hopper a sources of stress for parents of a sick neonate a
literature review Pediatr Nurs 2000 30 29ndash32
5 Davis l edwards H Mohay H wollin J The impact of very
premature birth on the psychological health of mothers Early Hum
Dev 2003 73 61ndash70
6 Bernazzani O saucier J-F David H Borgeat F Psychosocial
predictors of depressive symptomatology level in postpartum
women J Affect Disord 1997 46 39ndash49
7 Field T infants of depressed mothers Infant Behav Dev 1995 18
1ndash13
8 Kaplan Ps Bachorowski J-a Zarlengo-strouse P child-directed
speech produced by mothers with symptoms of depression fails
to promote associative learning in 4-month-old infants Child Dev
1999 70 560ndash570
9 ward K Perceived needs of parents of critically ill infants in
a neonatal intensive care unit (nicU) Pediatr Nurs 2001 27
281ndash286
10 lai Hl chen cJ Peng Tc et al randomized controlled trial of music
during kangaroo care on maternal state anxiety and preterm infantsrsquo
responses Int J Nurs Stud 2006 43 139ndash146
8 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
11 Tallandini Ma scalembra c Kangaroo mother care and mother-
premature infant dyadic interaction Infant Ment Health J 2006 27
251ndash275
12 Ohgi s Fukuda M akiyama T Gima H effect of an early intervention
programme on low birthweight infants with cerebral injuries
J Paediatr Child Health 2004 40 689ndash695
13 Kaaresen Pi ronning Ja Ulvund se Dahl lB a randomized
controlled trial of the effectiveness of an early-intervention program
in reducing parenting stress after preterm birth Pediatrics 2006
118 e9ndash19
14 Melnyk BM Feinstein nF alpert-Gillis l et al reducing premature
infantsrsquo length of stay and improving parentsrsquo mental health
outcomes with the creating opportunities for parent empowerment
(cOPe) neonatal intensive care unit program a randomized
controlled trial Pediatrics 2006 118 e1414ndash1427
15 Jotzo M Poets cF Helping parents cope with the trauma of
premature birth an evaluation of a trauma-preventive psychological
intervention Pediatrics 2005 115 915ndash919
16 Pearson J andersen K evaluation of a program to promote positive
parenting in the neonatal intensive care unit Neonatal Netw 2001
20 43ndash48
17 roman l lindsay J Boger r et al Parent-to-parent support
initiated in the neonatal intensive care unit Res Nurs Health 1995
18 385ndash394
18 Meyer ec coll cTG lester BM Boukydis cFZ McDonough sM Oh w
Family-based intervention improves maternal psychological well-
being and feeding interaction of preterm infants Pediatrics 1994
93 241ndash246
PaeDiaTrics anD cHilD HealTH 184 19
19 Preyde M ardal F effectiveness of a parent ldquobuddyrdquo program for
mothers of very preterm infants in a neonatal intensive care unit
CMAJ 2003 168 969ndash973
20 Hurst i One size does not fit all Parentsrsquo evaluations of a support
program in a newborn intensive care nursery J Perinat Neonatal
Nurs 2006 20 252ndash261
Practice points
bull Parents of sick neonates experience significant distress and
exhibit higher levels of stress anxiety and depression than
parents of healthy infants
bull educational support emotional support and increased
motherndashinfant contact have been shown to promote maternal
well-being
bull emotional support for fathers has been largely neglected in
the research literature
bull Parents benefit from a choice of supportive facilities which
could include face-to-face sessions with health professionals
telephone support hospital visitation parent-to-parent
support and unit-based group support meetings
bull Parentsrsquo support needs can change during their infantrsquos
hospitalization and not all parents want or benefit from the
provision of additional information and emotional support in
the neonatal unit
9 copy 2008 elsevier ltd all rights reserved
Personal Practice
When should enteral feeds be started in preterm infantsnicholas D embleton
AbstractPaediatricians are regularly faced with the question of when best to start
enteral feeds in preterm infants this is important as longer term out-
come may be compromised by sub-optimal nutrition in early life clinical
factors that may affect the decision to start and the risk and benefits
are discussed
Keywords breast milk feeding nutrition parenteral nutrition
Key points in the history
Alice is lsquonutritionally vulnerablersquo and whilst this may not be immediately apparent it will affect her long term outcome Her energy stores are extremely limited and consist primarily of pro-tein She has less than 5 fat and little energy associated with stored glycogen She is losing about 1 gkgd protein equivalent so she needs at least that and a minimum of 50ndash60 kcalkg of energy just to maintain the status quo let alone grow
Her weight is on the 25th centile Review of any antenatal his-tory may reveal whether fetal growth was normal Fetal growth retardation can occur with a weight greater than 10th centile The presence of antenatal absent or reversed end diastolic flow in the umbilical artery indicates poor gut blood flow This increases the risk of necrotizing enterocolitis (NEC) and might suggest a more cautious approach to starting feeds1
She has no important cardiovascular problems but if she were hypotensive gut blood flow may be low There is no umbilical
Nicholas D Embleton BSC (Hons) MBBS (Hons) MD FRCPCH is Consultant in
Neonatal Medicine at Newcastle Neonatal Service Royal Victoria
Infirmary Newcastle upon Tyne NE1 4LP UK
Should you start feeds at a day of age
alice was born following spontaneous labour at 30 weeksrsquo
gestation she weighed 1300 g and is now 18 h old she was
briefly ventilated and then extubated to continuous positive
airway pressure 12 h ago in 35 oxygen she has had caffeine
citrate but still has intermittent episodes of self-correcting
apnoea she was commenced on iv 10 dextrose but this was
replaced by a parenteral amino acid solution (referred to as
lsquotPnrsquo) along with intralipid at 0900 this morning serum glucose
is 11 mmoll and blood pressure is 42 systolic
PaeDiatrics anD cHilD HealtH 184 20
arterial catheter in situ but there is no good evidence that this should delay the decision to start feeds Her glucose is high but this is quite common in a baby like this Could this be a sign of sepsis Caffeine does not affect the incidence of NEC2 The great-est risk factor for NEC in this case is prematurity
What else might be found on examination
Up until 24 h ago she was swallowing large amounts of amniotic fluid What will have changed since then
General examination should confirm peripheral perfusion lsquogestaltrsquo view (does she look lsquowellrsquo) and cardiovascular status lsquoBowel soundsrsquo are not usually helpful
The most important variable likely to affect gut perfusion is the arterial duct Precordial lsquoheaversquo and a loud murmur are sug-gestive but it is possible to have a significant ductal shunt in a baby with a normal examination Cardiac ultrasound will con-firm this diagnosis It might be better to treat a large shunt first with indometacin and to delay starting feeds for a further 24 h
It is not possible to assess gut perfusion clinically but normal perfusion elsewhere (adequate urine output usually indicates adequate renal perfusion) would be reassuring Most preterm babies have a few abdominal lsquoloopsrsquo visible but a distended abdomen with many palpable loops suggests ileus This might be secondary to sepsis or poor gut blood flow Preterm babies do not pass much meconium in the first 24ndash48 h
Balance of risks between starting and withholding feeds
Alice requires 35ndash4 gkgd of protein and 120 kcalkgd to grow3 This will initially be provided parenterally Delaying feeds increases the risk of gut villous atrophy and prolongs the need for lsquototal parenteral nutrition (TPN)rsquo TPN requires intravenous access and so increases the risk of sepsis and when prolonged use is required combined with the lack of enteral feeding may result in hepatic impairment
Delaying feeds may allow a gut that has been chronically under-perfused to re-establish more normal perfusion although normal gut endocrine function digestive enzyme upregulation and motility require a source of intraluminal nutrients1 A recent study suggested benefit from delaying the introduction of feeds4 but methodologi-cal problems exist5 Although a Cochrane meta-analysis suggested no benefit only two studies were included6 A large UK-based trial is examining the effect of early or late feeding in preterm infants who were born growth retarded following identification of antena-tal absent or reversed end diastolic flow in the umbilical artery7
When starting feeds what volume should be used
There are no good data to guide this decision We start with 24 mlkg (1 mlkgh) and then increase by this amount each day Most babies achieve full enteral feeds (ge150 mlkgd) by a week of age Feeding guidelines improve the outcome8 Measure-ment or assessment of gastric aspirates is not consistently useful in predicting subsequent feeding intolerance or development of NEC Aspirate volumes equivalent to or sometimes greater than the amount given in the preceding 1ndash2 h are usually normal Most aspirates have a greenish colour Thick bloody or intensely bile-stained aspirates require detailed assessment
0 copy 2008 elsevier ltd all rights reserved
Personal Practice
What else affects decisions and outcome
Feeding success is affected by sepsis and NEC Scrupulous atten-tion should be paid to hand washing and intravenous access and blood sampling should be minimized There is no good evidence to support the routine use of pro-kinetic agents or H2 blockers
The most important clinical intervention affecting the occur-rence of NEC is the use of breast milk9 All efforts should be directed at persuading parents of the benefits and supporting the process Some clinicians delay starting feeds for a further 24 h whilst expressed breast milk becomes available Donor breast milk might be equally efficacious10
RefeRenceS
1 Dorling J Kempley s leaf a Feeding growth restricted preterm
infants with abnormal antenatal Doppler results Arch Dis Child Fetal
Neonatal Ed 2005 90 F359ndash363
2 schmidt B roberts rs Davis P et al caffeine therapy for apnea of
prematurity N Engl J Med 2006 354 2112ndash2121
PaeDiatrics anD cHilD HealtH 184 20
3 embleton nD Pang n cooke rJ Postnatal malnutrition and growth
retardation an inevitable consequence of current recommendations
in preterm infants Pediatrics 2001 107 270ndash273
4 Berseth cl Bisquera Ja Paje VU Prolonging small feeding volumes
early in life decreases the incidence of necrotizing enterocolitis in
very low birth weight infants Pediatrics 2003 111 529ndash534
5 Menon G Boyle eM embleton nD et al introduction of enteral
feeds in preterm infants Pediatrics 2004 114 327ndash328
6 Kennedy Ka tyson Je chamnanvanikij s early versus delayed
initiation of progressive enteral feedings for parenterally fed low
birth weight or preterm infants Cochrane Database Syst Rev 2000
cD001970
7 wwwnpeuoxacukadept
8 Patole sK de Klerk n impact of standardised feeding regimens on
incidence of neonatal necrotising enterocolitis a systematic review
and meta-analysis of observational studies Arch Dis Child Fetal
Neonatal Ed 2005 90 F147ndash151
9 lucas a cole tJ Breast milk and neonatal necrotising enterocolitis
Lancet 1990 336 1519ndash1523
10 Boyd ca Quigley Ma Brocklehurst P Donor breast milk versus
infant formula for preterm infants systematic review and meta-
analysis Arch Dis Child Fetal Neonatal Ed 2007 92 F169ndash175
1 copy 2008 elsevier ltd all rights reserved
self-assessment
Case 1A term male infant born to consanguineous parents is assessed at 24 h of age due to poor feeding profuse yellow watery diar-rhoea and irritability He weighed 32 kg at birth and delivery was uneventful There was no polyhydramnios He has been breastfed since birth On examination he is pale with a non-tender but distended abdomen and reduced bowel sounds His weight is 275 kg and he looks dehydrated Examination is otherwise normal
Initial investigations (normal values in parentheses) showed
sodium 149 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 65 mmollitre (25ndash75)
creatinine 147 μmollitre (40ndash110)
chloride 119 mmollitre (95ndash105)
haemoglobin 172 gdl (140ndash200)
White blood cell count 80 times 109litre (100ndash260)
Platelet count 302 times 109litre (150ndash400)
arterial blood gas
ph 720 (730ndash745)
PcO2 23 kPa (46ndash60)
Bicarbonate 68 mmollitre (220ndash260)
Base excess minus186 mmollitre (minus20 to +20)
lactate 59 mmollitre (06ndash24)
An abdominal X-ray shows distended bowel loops with no intramural thickening or pneumoperitoneum (Figure 1)
He was given nil by mouth and received intravenous fluids and antibiotics His dehydration improved but the metabolic acidosis and diarrhoea persisted despite receiving no enteral feeds and the commencement of total parenteral nutrition Blood and stool cultures were negative
1 Which of the following best describes these results Choose ONE answer ONLY from the followingA Hypernatraemia hyperchloraemic metabolic acidosis
with increased anion gapB Hypernatraemia hyperchloraemic metabolic acidosis
with normal anion gap
Manish Sadarangani BM BCh MA MRCPCH is Clinical Research Fellow
at the Department of Paediatrics University of Oxford Centre for
Clinical Vaccinology and Tropical Medicine Churchill Hospital
Oxford OX3 7LJ UK
Shabna Rajapaksa MB BChir MA MRCPCH is Specialist Registrar in
Paediatrics at the Paediatric Intensive Care Unit John Radcliffe
Hospital Oxford OX3 9DU UK
Nicholas Mann MD FRCP FRCPCH DCH is Consultant Paediatrician at the
Department of Paediatrics Royal Berkshire Hospital Reading RG1
5AN UK
self-assessment
C Hypernatraemic dehydration and compensated metabolic acidosis
D Acute renal failureE Renal tubular acidosis
2 What is the likely diagnosis Choose ONE answer ONLY from the followingA Hirschsprung disease ndash long segmentB Cystic fibrosis with meconium ileusC Microvillus inclusion diseaseD Cowrsquos milk protein intoleranceE Lactose intolerance
3 What is the investigation of choice Choose ONE answer ONLY from the followingA Rectal biopsy with staining for acetylcholine receptorsB Immunoreactive trypsinC Gastrointestinal endoscopy and biopsyD Stool microscopy and cultureE Stool reducing substances
Case 2A 4-year-old boy presents with a 3 d history of jaundice and a florid rash He has had orange urine and there is no change in his stool colour His family originate from Kosovo and have lived in the UK for the last 8 years He has never left the UK There is no history of blood transfusion or sex-ual abuse The grandmother was recently diagnosed with hepatitis B
On examination he is well apyrexial and mildly jaundiced with cervical and axillary lymphadenopathy He has an exten-sive papular rash over the face extremities and trunk (Figure 2) There is 3 cm hepatomegaly with no splenomegaly or ascites Examination is otherwise normal
Figure 1 abdominal X-ray of baby
Paediatrics and child health 184 202 copy 2008 elsevier ltd all rights reserved
self-assessment
Initial investigations are as follows
haemoglobin 110 gdl (113ndash135)
White blood cell count 108 times 109litre (50ndash150)
Platelet count 278 times 109litre (150ndash400)
inr 10 (08ndash12)
aPt ratio 10 (08ndash13)
sodium 140 mmollitre (135ndash145)
Potassium 42 mmollitre (35ndash50)
Urea 56 mmollitre (25ndash75)
creatinine 65 μmollitre (45ndash120)
total bilirubin 66 μmollitre (0ndash15)
conjugated bilirubin 23 μmollitre (0ndash10)
alanine aminotransferase (alt) 2033 iUlitre (0ndash35)
alkaline phosphatase 987 iUlitre (71ndash234)
Gamma-glutamyl transferase (GGt) 870 iUlitre (0ndash51)
1 What is the name of this rash Choose ONE answer ONLY from the followingA Erythema multiformeB Erythema migransC GianottiminusCrosti syndromeD EczemaE Dermatitis herpetiformis
2 What is the most likely diagnosis Choose ONE Answer ONLY from the followingA Autoimmune hepatitisB Hepatitis BC Hepatitis DD Wilson diseaseE Alpha-1 antitrypsin deficiency
3 What is the best means of management Choose ONE answer ONLY from the followingA Isolation until the jaundice disappearsB ImmunosuppressionC Copper chelating agents and genetic counsellingD Patient and family education with consideration of
antiviral agentsE Liver transplantation
Case 3A 10-month-old boy presents with 3 weeks of vomiting and constipation ndash he is passing hard stools every 2ndash3 days He has fallen from the 9th to below the 04th centile in the last 6 weeks He passed meconium within the first 24 h of life On examina-tion he looks pale and there are some dysmorphic features ndash a short nose long philtrum and wide mouth He has normal heart sounds with a grade 3 ejection systolic murmur loudest at the upper right sternal edge Examination is otherwise normal
Initial investigations are as follows
haemoglobin 91 gdl (113ndash141)
total white blood cell count 124 times 109litre (60ndash170)
Platelet count 407 times 109litre (150ndash400)
sodium 144 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 78 mmollitre (25ndash75)
creatinine 78 μmollitre (45ndash120)
albumin 52 glitre (35ndash50)
corrected calcium 384 mmollitre (238ndash263)
Phosphate 167 mmollitre (099ndash157)
1 What is the most likely diagnosis Choose ONE answer ONLY from the followingA HyperparathyroidismB Acute leukaemiaC Williams syndromeD Hypervitaminosis DE Familial hypocalciuric hypercalcaemia
2 Which investigation would be most useful in establishing the diagnosis Choose ONE answer ONLY from the followingA Intact parathyroid hormone assayB Blood filmC Fluorescent in-situ hybridization for 7q1123 deletionD 25-hydroxyvitamin D assayE Urine calciumcreatinine ratio
3 Which of the following treatments would not be suitable for this patient Choose ONE answer ONLY from the followingA Low calcium dietB Normal saline infusionC FurosemideD CorticosteroidsE Bisphosphonates
Case 4A 10-week-old girl presents with a 2-day history of poor feed-ing Her mother has been concerned about weakness since birth She only has a flicker of movement in the arms none in the legs and has a weak cry She has been passing urine and opening her bowels normally She was born at full term by normal delivery and did not require any resuscitation at birth Normal fetal movements were felt antenatally and there was no polyhydramnios She is the first child of non- consanguineous parents and there is no significant family his-tory On examination she is alert and fixing and following appropriately She has a weak cry and a weak suck There is reduced central and peripheral tone with marked head lag
Figure 2 rash found on examination
Paediatrics and child health 184 203 copy 2008 elsevier ltd all rights reserved
self-assessment
Muscle power is grade 3 out of 5 in the arms and legs There is no muscle or tongue fasciculation and she has absent reflexes throughout The remainder of the examination is normal
Electromyogram shows irregular polyphasic motor unit potentials with marked instability consistent with a dener-vating and re-innervating process (Figure 3)
1 Which of the following additional investigations may be helpful Choose ONE answer ONLY from the followingA Nerve conduction studiesB Creatine kinase assayC Muscle biopsyD SMN1 gene analysisE All of the above
2 What is the most likely cause of this childrsquos symptoms Choose ONE answer ONLY from the followingA Congenital myotonic dystrophyB Duchenne muscular dystrophyC PraderminusWilli syndromeD Spinal muscular atrophyE Mitochondrial myopathy
3 What is the mode of inheritance of this disease Choose ONE answer ONLY from the followingA X-linked recessiveB Autosomal recessiveC Autosomal dominantD MitochondrialE Sporadic
Case 5A 13-year-old girl presents with a 3-week history of fever up to 40degC night sweats and headache She has a reduced appetite with some weight loss She has no other specific symptoms She was on holiday in China 7 months ago On examination she looks well and has a temperature of 387degC There is no lymphadenopathy and no rashes Examination is entirely normal
Results of investigations are as follows
haemoglobin 126 gdl (120ndash160)
total white blood cell count 132 times 109litre (43ndash108)
neutrophil count 115 times 109litre (25ndash75)
Platelet count 244 times 109litre (150ndash400)
Blood film neutrophilia with left shift
erythrocyte sedimentation rate 63 mmh (1ndash20)
c-reactive protein 219 mglitre (0ndash5)
Blood culture Streptococcus intermedius
from anaerobic bottle only
csf culture negative
Magnetic resonance imaging (MRI) of the brain shows acute frontal sinusitis with a large intracranial frontal extra-dural empyema (Figure 4)
1 Which of the following would be appropriate management Choose ONE answer ONLY from the followingA A 12-week course of intravenous antibioticsB Drainage of the frontal sinus followed by 2 weeks of
intravenous antibioticsC Drainage of the empyema followed by 2 weeks of
intravenous antibioticsD Drainage of the empyema and the frontal sinus
followed by 2 weeks of oral antibiotics
1151
1152
1153
1154
1155
1156
1157
1158
1159
1200
50ms 1mV
Figure 3 electromyogram recording from the patient Figure 4 Parasagittal section from mri scan of patient
Paediatrics and child health 184 204 copy 2008 elsevier ltd all rights reserved
self-assessment
E Drainage of the empyema and the frontal sinus followed by 8 weeks of intravenous antibiotics
2 Streptococcus intermedius is a potential pathogen in which of the following infections Choose ONE answer ONLY from the followingA Liver abscessB Urinary tract infectionC MeningitisD Thoracic empyemaE Pneumonia
3 Which of the following statements regarding lsquopyrexia of unknown originrsquo in children is false Choose ONE answer ONLY from the followingA Malignancy is the underlying pathology in 5ndash15 of
casesB An aetiology will be found in over 90 of casesC The most common cause is infectionD A rheumatological cause is found in 10ndash20 of casesE Familial Mediterranean fever can occur in children of
non-Mediterranean ethnicity
Answers
Case 11 AThe anion gap is a useful tool to differentiate the causes of a metabolic acidosis It is calculated by the equation
Anion gap = [Na K ] [Cl HCO ]3+ + minus minus+ minus +
It represents the effect of unmeasured anions on the plasma pH and is normally 10ndash18 mmollitre
2 CMicrovillus inclusion disease is a severe autosomal recessive enteropathy that is typically apparent within hours or days after birth It is the second most common cause of protracted diarrhoea in the newborn after infectious causes It is characterized by severe yellow watery diarrhoea and malabsorption due to hypoplasia andor atrophy of the villi of the small intestine secondary to an inherited defect in the brush border membrane This results in severe dehydration malnutrition and metabolic acidosis due to bicarbonate loss from the gut
3 CDiagnosis of microvillus inclusion disease is made on small bowel biopsy Electron microscopy findings are of intracellular brush border inclusions and densely packed apical cytoplasmic vesicular bodies indicating microvillous atrophy There is no cure Treatment is supportive with total parenteral nutrition and consideration of small bowel transplantation
Further reAding
Goulet O ruemmele f causes and management of intestinal failure
in children Gastroenterology 2006 130(suppl 1) s16ndash28
rhoads Jm Vogler rc lacey sr et al microvillus inclusion disease
In vitro jejunal electrolyte transport Gastroenterology 1991
100 811ndash817
Case 21 CGianottindashCrosti syndrome is a distinct self-limiting rash commonly associated with viral infections in children between 2 and 6 years of age It presents as multiple pink to redminusbrown papules or papulovesicles which may be pruritic and can become confluent Gianotti and Crosti initially described the exanthema as associated with hepatitis B virus and they termed it papular acrodermatitis of childhood It can occur in several viral diseases eg hepatitis A B and C coxsackie viruses and cytomegalovirus
2 BHepatitis is a syndrome characterized by inflammation or injury of liver cells which may develop into cell necrosis and subsequently fibrosis andor cirrhosis Biochemically there are raised liver enzymes The degree of transaminase elevation does not correlate with the severity of the disease process Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of viral hepatitis
3 DHepatitis B infection is transmitted via blood sexually or vertically Infection may be acute or chronic Diagnostic markers are the presence of surface antigen (HBsAg) and HBV DNA The presence of e antigen (HBeAg) indicates high infectivity Infected newborns have a 95 risk of becoming carriers this risk decreases with infection acquired later in childhood Approximately 15ndash25 of HBV carriers will die from cirrhosis or hepatocellular carcinoma Extrahepatic findings are more common in older children and include membranous glomerulonephritis and GianottiminusCrosti syndrome Fulminant hepatic failure occurs in severe cases resulting in persistent jaundice encephalopathy and coagulopathy Management includes counselling family members monitoring for ongoing liver disease and consideration of antiviral therapy
Further reAding
Brandt O abeck d Gianotti r Burgdorf W Gianotti crosti
syndrome J Am Acad Dermatol 2006 54 136ndash145
slowik mK Jhaveri r hepatitis B and c viruses in infants and
young children Semin Pediatr Infect Dis 2005 16 296ndash305
Case 31 CHypercalcaemia is uncommon in infancy The most common symptoms in this age group are irritability vomiting and constipation It may be a manifestation of Williams syndrome vitamin D or calcium excess as well as disorders associated with reduced bone formation such as hypophosphatasia or increased bone resorption such as malignancy Occasionally
Paediatrics and child health 184 205 copy 2008 elsevier ltd all rights reserved
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-
SympoSium neonatology
Temperature control in the neonateandrew lyon
Abstractthe control of body temperature is a challenge to the newborn baby
particularly if immature or sick Behavioural responses to environmental
temperature changes are almost non-existent the preterm baby has lim-
ited ability to mobilize energy sources to combat high heat losses par-
ticularly from evaporation there is evidence that many preterm babies
are still being allowed to get cold during stabilization and resuscitation
a low temperature at the time of admission to a neonatal unit is inde-
pendently associated with an increased mortality in the preterm infant
preventing evaporative heat losses at this time can abolish hypothermia
on admission Further studies are needed to determine the optimum
thermal management immediately after delivery there are no studies
that show any difference in outcome for preterm babies nursed in incu-
bators compared to those under radiant heaters High transepidermal
water loss (teWl) results in increased fluid and heat loss in the preterm
baby this can be managed by increasing environmental humidity al-
though this may be more difficult when babies are nursed under radiant
heaters nursing the baby in high humidity reduces teWl but more work
is needed to show if a reduction in water movement has an adverse ef-
fect on the rate of maturation of the skin the way a baby interacts with
their environment is always changing and whatever temperature and
humidity settings are first used it is necessary to monitor continuously
the thermal balance the continuous measurement and display of a cen-
tral and a peripheral temperature gives an early indication of cold stress
before there is any fall in the babyrsquos core temperature
Keywords centralndashperipheral temperature difference humidity
newborn preterm temperature control transepidermal water loss
Introduction
Children and adults maintain a constant deep body tempera-ture over a wide range of ambient thermal conditions (homeo-thermic) This is achieved by physiological and behavioural responses that control the rate at which heat is produced or lost The newborn infant is also homeothermic but control of body temperature can only be achieved over a narrower range of ambient conditions The preterm infant has even greater dif-ficulty in body temperature control and the most immature infants behave at times as if they are poikilothermic ndash their body
Andrew Lyon MA MB FRCP FRCPCH is Consultant Neonatologist at the
Simpson Centre for Reproductive Health Royal Infirmary of Edinburgh
Little France Edinburgh EH16 4SA UK
paeDiatRiCS anD CHilD HealtH 184 15
temperature tending to drift up and down with the ambient tem-perature The aim in neonatal care is to provide a thermal envi-ronment which keeps body temperature in the normal range and which does not stress the infant to produce or lose large amounts of heat
The importance of keeping newborn babies warm has been known for centuries1 In the 1950s William Silverman and others showed a clear link between temperature control and neonatal mortality In a series of randomized controlled trials they showed that keeping babies warm in incubators resulted in an absolute reduction in mortality of 2523 In many of these studies a sig-nificant numbers of babies were under 1000 g birthweight and the improvement in survival was seen in all birthweight groups No other single change in practice has had such a dramatic effect on mortality of the newborn baby
The EPICure study of a cohort of babies under 26 weeksrsquo ges-tation delivered in the UK in 1995 showed that low admission temperature was an independent risk factor for neonatal death even after adjustment for other known risks4 In this population study 30 43 and 58 of babies at gestations 25 24 and 23 weeks respectively who were admitted to neonatal units had an admission temperature below 35 degC The report of the CESDI 2728 project showed that in babies born at 27 and 28 weeksrsquo gestation an admission temperature below 36 degC was found in 73 of those who died compared with 59 in those who survived5
The importance of early temperature as a predictor of out-come in preterm babies is shown by its inclusion in risk scoring systems such as the Clinical Risk Index for Babies (CRIB)6 and the Score for Neonatal Acute Physiology ndash perinatal extension (SNAPPE-II)7
Extended periods of cold stress can lead to harmful side effects including delayed adaptation to extrauterine life hypoglycaemia respiratory distress hypoxia metabolic acidosis coagulation defects acute renal failure necrotizing enterocolitis failure to gain weight or weight loss and death
Many factors are associated with an increased risk of hypo-thermia These include prematurity intrauterine growth restric-tion central nervous system damage and congenital defects such as abdominal wall defects where bowel is exposed to the air
Induced cooling may help protect the brain of the asphyxiated term newborn8 but prolonged exposure to cold in babies with no brain injury must be avoided Overheating the baby with sus-pected asphyxial brain injury must also be prevented as hyper-thermia may increase the degree of damage9
Temperature control at delivery
The temperature of the fetus is between 05 and 1degC higher than that of the mother At birth the infant is exposed to a colder environment than in utero Although some heat loss may be important in stimulating onset of breathing and other adaptive mechanisms10 it is important to avoid a continuing drop in body temperature In the term baby this is achieved by drying wrapping and placing under a radiant heater if resuscitation is needed
The preterm baby often needs a period of stabilization or resuscitation and traditionally has been placed naked on a resuscitaire Despite the use of direct radiant heat studies
5 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
such as EPICure and CESDI 2728 have shown that many of these babies are cold by the time of admission to the neo-natal unit In a study from the USA of 5277 babies with a birthweight below 1500 g in the Neonatal Research Network only 108 had an admission temperature of 37 degC or above In nearly half the babies the first recorded temperature was below 36 degC Admission temperature was inversely related to mortality (28 increase per 1 degC) and late-onset sepsis There was an association of low temperature with the need for intubation at delivery suggesting that radiant heat alone had not been sufficient to offset the heat losses during prolonged resuscitation11
A baby exchanges heat with their environment by conduc-tion radiation convection and evaporation The preterm baby is at high risk of net heat loss because of a high surface area to volume ratio and increased transepidermal water loss resulting in heat lost by evaporation The normal surge in metabolic rate which occurs after birth is much reduced limiting the production of heat from the mobilization of brown fat The development in the control of skin blood flow is also delayed in the imma-ture baby reducing their ability to maintain heat by peripheral vasoconstriction12
Evaporation is the major mechanism of heat loss during resus-citation The baby will lose 560 cal for every millilitre of water evaporated from the skin (the heat of evaporation) Vohra et al have shown that using polyethylene occlusive skin wrapping around the body up to the neck during resuscitation of preterm babies under 28 weeksrsquo gestation significantly improves the central temperature on admission to the neonatal unit13 This is due to a reduction in evaporative heat losses In this random-ized study comparing rectal temperature on admission of babies wrapped at birth with those managed without wrapping body size was an important determinant of heat loss the mean rectal temperature increasing by 021degC with each 100 g increase in birthweight
The use of plastic bags leaving just the head exposed has also been found to be effective in reducing transepidermal water and heat losses during resuscitation14 It is important not to expose the skin once the baby is in the plastic bag ndash clini-cal inspection and auscultation can be done through the bag and if vascular access is needed a small hole can be cut in the plastic
Whether a plastic bag or occlusive dressing is used it is important to remember that there is still significant heat losses from the head which should be covered with a hat during resus-citation and stabilization15
Concern has been expressed about hyperthermia in some babies possibly secondary to the use of occlusive dressings or plastic bags16 Two babies in the study by Vohra et al13 had a rectal temperature above 375 degC In a small study from Edin-burgh 11 of 27 babies under 28 weeksrsquo gestation managed in plastic bags were found to have an admission temperature above 375 degC Of these eight were above this temperature from birth possibly associated with a maternal pyrexia while in the other three the temperature increased (by no greater than 06 degC) after being placed in the bag17
Preventing evaporative heat loss using occlusive dressings or plastic bags has been shown to be effective in preventing hypothermia after delivery at least in babies under 29 weeksrsquo
paeDiatRiCS anD CHilD HealtH 184 15
gestation A Cochrane review concludes that in this group con-sideration should be given to their use in the delivery suite18
No study has yet been powered to show that these treatments reduce neonatal mortality and long term outcome has not been evaluated Further large high quality randomized controlled tri-als are still needed Not least we need to confirm that the mem-brane wrapped around the infantrsquos trunk does not damage the immature skin
Transport
The transport of the newborn baby particularly the preterm infant presents many challenges Transport is not only between units but also within a hospital eg from the delivery suite to the neonatal unit or to and from the radiology department or the operating room
The most effective mode of transport within a hospital building will depend on the local configuration Newly designed neonatal units should be closely linked to the delivery suite to prevent the need for transport over long distances along draughty corri-dors A randomized controlled study comparing transfer from the delivery suite to the neonatal unit of babies under 28 weeksrsquo ges-tation using a radiant warmer or a transport incubator showed no difference in admission temperature in the two groups19 All babies in both groups had been managed with occlusive wrap-ping in the delivery room
Transfer between units is most commonly by road in an ambulance Although incubators are heated there is likely to be high radiative heat losses especially in cold weather This can be reduced by covering the incubator and by using blankets around the baby Evaporative heat losses can be reduced by using a plas-tic bag There will be high evaporative heat losses from the respi-ratory tract if ventilator gases are not heated and humidified Heated gel mattresses which warm patients through release of latent heat of crystallization can be used during transport The baby gains heat by conduction Safe use of this device is critically dependent on gel temperature at the point of activation20
Thermal care within the neonatal unit
The full-term newborn infant will maintain a normal temperature if nursed fully dressed in a cot in a warm room Recommenda-tions for optimum environmental conditions for nursing healthy infants in the newborn period have been published21
Skin-to-skin contact is an effective way of maintaining body temperature even in the very preterm infants2223
The preterm baby even if well may be unable to maintain an adequate temperature without some additional source of heat There are a variety of ways of providing this including incuba-tors radiant heaters and heated mattresses The heated gel- or water-filled mattress is very effective in helping maintain the temperature of the well preterm baby while allowing easy access for parents and staff
Clothes act as a significant thermal barrier to heat loss New-born infants needing intensive or high dependency care are often nursed naked to allow close observation and easy access for examination and treatment This significantly affects tempera-ture control as the resistance to heat loss of a naked baby is three times less than that of a clothed wrapped infant2425
6 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Control of the thermal environment is important for all babies but it is the unwell immature babies who present the greatest challenge They are usually nursed either in an incubator or on an open platform under a radiant heater The early clinical trials of Silverman and others showed that the use of incuba-tors to keep babies warm improved outcome There have never been any controlled studies that show that radiant heaters are as effective clinically Babies nursed with similar skin temperatures have a higher basal metabolic rate when managed under radi-ant heaters compared with incubators26 However no study has shown any significant difference in outcome for babies nursed using either of these devices although Meyer et al27 reported a non-significant trend to better outcome in babies nursed under a radiant heater
Transepidermal water loss
Silverman in the 1950s showed that babies are better able to maintain their body temperature in a humid environment com-pared with a dry environment28
In the 1970s it became possible to measure the evaporation rate of water from the skin surface29 Transepidermal water losses (TEWL) are high in the immature baby At 26 weeksrsquo gestation on day 1 of life the baby can lose over 50 kcalkg by evapora-tion compared with less than 5 kcalkg in the term infant30 Data from Hammerlund et al30 suggest that the skin matures rapidly after birth and adult losses are reached around 10 d of age in all babies After this time the major source of heat loss in all babies is from radiation More recently others have shown that in the very immature baby the maturation of the skin may take longer and 30 weeksrsquo corrected age is a better estimate of the time taken to reach adult TEWL31 In practical terms the amount of trans-epidermal fluid losses after about 14 d are unlikely to remain a major problem
Evaporative water loss from the skin depends on the ambi-ent water vapour pressure irrespective of how the baby is being nursed The high rate of evaporation during care under a radiant heater is due to the low ambient water vapour pressure and not any direct effect of non-ionizing radiation on the skin32
TEWL results in loss of both heat and fluid Under a radi-ant heater the temperature of the baby is maintained because of radiant heat gain but the large fluid losses can be a seri-ous problem Various interventions can help reduce evaporative fluid losses mainly from the skin but also from the respiratory tract
IncubatorsWithin an incubator it is relatively easy to raise the ambient water vapour pressure by introducing humidity within the can-opy The use of a relative humidity of 80 for the first 7ndash10 d of life significantly reduces TEWL in even the most immature infant30 Modern designs use a sealed water system to produce the humidity minimizing the concerns about possible increased infection risk in humidified incubators
Opening the incubator portholes results in a rapid fall in humidity although the air temperature within the canopy is maintained The handling of babies within incubators has been shown to be associated with increased thermal stress33 and it is likely that this is due to the fall in environmental humidity
paeDiatRiCS anD CHilD HealtH 184 15
resulting in increased evaporative heat losses Increasing the air temperature will compensate for the heat loss but incubators are relatively slow to respond to such changes
High humidity within the incubator can cause lsquorain outrsquo on the inside of the canopy This is caused by water condensing on the cold walls and can be minimized by ensuring an adequate environmental temperature within the nursery (around 28 degC)
Radiant heatersTEWL is the major problem in babies nursed under radiant heaters A shield or plastic blanket can be used to cover the baby and create a humidified microenvironment Warm humid-ified air can be passed under the shield or blanket but care must be taken to control the temperature and to make sure it does not affect the skin servo probe attached to the baby If the cover is removed the humidity falls rapidly and the baby starts to lose large amounts of fluid The radiant heater will compen-sate for any fall in the babyrsquos temperature but fluid losses are a concern
Maintenance of skin integrityDamage to the fragile skin of the preterm baby occurs easily and results in a significant increases both in TEWL and the risk of infection Maintaining skin integrity is very important and any adhesives on the skin should be kept to a minimum
Skin coveringsTransparent adhesive dressings on the skin reduce fluid loss but cause significant damage making them impractical
Use of semipermeable non-adhesive dressings lowers TEWL and reduces the bacteria number in the covered skin34 In a ran-domized controlled trial in infants less than 1000 g the skin cov-ered with a semipermeable membrane was in better condition but there were no significant differences in fluid requirements or electrolyte status35
Emollients are used to cover the skin and prevent fluid loss They have been shown to be safe and do not cause burns when exposed to radiant heat or phototherapy Their use reduces excessive drying skin cracking and fissuring However the effect of these products wears off after about 3 h necessitating repeated application36 Treated infants had better skin scores and there were no differences in bacterial skin counts fungal counts or colonization patterns or fluid requirements and electrolyte status37
Ventilator humidityThere can be high fluid and heat losses from the respiratory tract of the ventilated baby It is important to use adequate humidifi-cation in all ventilator circuits
PhototherapyThe effect of phototherapy on TEWL is variable No change was found in a group of thermally stable infants38 yet others have reported an increase in TEWL despite skin temperature and rela-tive humidity remaining unchanged39 Rather than increase fluid intake just because phototherapy has been started fluid balance should be individually monitored and adjusted if necessary
Modern phototherapy units produce little heat but there is still some increase in the temperature of the top of the incubator
7 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
canopy This will reduce radiative heat losses and the incubator air temperature may have to be reduced to prevent a rise in the babyrsquos temperature
Transepidermal water loss and skin maturationTransepidermal movement of water is essential for the acceler-ated maturation of the skin of the immature baby40 It also helps in maintaining the epidermal barrier function41
Use of high ambient humidity in nursing preterm babies under 28 weeksrsquo gestation has been shown to reduce the rate of promo-tion of skin barrier development42
More work in the immature baby is needed to determine the optimum level and duration of environmental humidity as well as the associated benefits and risks of use and the effects of humidification on clinically important outcomes43
Temperature monitoring and its interpretation
The concept of the neutral thermal environment in which a baby uses a minimum of energy to maintain thermal stability has proven useful in determining the optimum environmental temperature for nursing the newborn baby4445 The published data are now old and do not include any allowance for added humidity This makes them less useful in the care of the very immature baby
The way a baby interacts with their environment is always changing and whatever settings are first used it is necessary to monitor continuously the thermal balance Continuous mea-surement of oxygen consumption to allow calculation of energy expenditure is not practical and in normal day-to-day care tem-perature monitoring is the only means of assessing the thermal stability of the baby
There is no single deep body temperature as this will vary depending on the metabolic rate of a particular tissue The brain has the highest temperature of any organ within the body It is however possible to find a central temperature that is representa-tive of deep body temperature Trends in this temperature reflect changes in the deep body temperatures of the body at least with sufficient accuracy for day-to-day clinical care
Traditionally rectal temperature has been used as the mea-sure of deep body temperature This is still used commonly in many countries but less so in UK There is a significant risk of damage to the mucosa of the rectum Also rectal temperature is unreliable being affected by the depth of insertion of the ther-mometer whether the baby has just passed a stool and by the temperature of the blood returning from the lower limbs It is difficult to retain the probes in the same position making this an unreliable site for continuous temperature monitoring
The temperature in the oesophagus at the level of the heart gives a measure of the temperature of the blood in the great veins returning from the body This is possibly the best overall representation of the lsquodeep body temperaturersquo Measurement of oesophageal temperature is however very invasive and not suit-able for clinical monitoring
The temperature of the skin over the liver or in the axilla reflects central temperature Actual values will be lower than the deep body temperatures but in the immature baby these sites can be used to show the trend in central temperature A more accurate measurement can be obtained by placing the
paeDiatRiCS anD CHilD HealtH 184 15
probe between the scapulae and a non-conducting mattress No tape is needed on the skin as the baby lies on the probe holding it in place If the probe is over an area of skin from which no heat can be lost by conduction convection radia-tion or evaporation then with heat flow from the centre of the body to the skin down a temperature gradient this area of skin will warm up to the same temperature as the bodyrsquos core This so-called zero heat flux temperature has been shown to be very close to the central temperature as measured by an oesophageal probe46
The measurement of a single temperature tells us how well the baby is maintaining that temperature but nothing about how much energy is being used to achieve thermal balance The continuous measurement and display of a central (abdominal axilla or zero heat flux) and a peripheral (sole of the foot) tem-perature detects cold stress with the peripheral temperature fall-ing before the central measurement changes
The preterm baby who appears to be comfortable in their environment will have a central temperature measured from a skin probe of 368ndash373 degC and a centralndashperipheral temperature difference of 05ndash1 degC An increasing centralndashperipheral tempera-ture difference particularly above 2 degC is usually due to cold stress and occurs before any fall in central temperature12
Hypovolaemic babies will vasoconstrict their peripheral circu-lation in an attempt to maintain blood pressure This results in an increase in the centralndashperipheral temperature difference but in such cases there are usually other signs of hypovolaemia such as rising heart rate and falling blood pressure12
A high central temperature particularly if unstable along with a wide centralndashperipheral gap is seen in septic babies47
Conclusion
Although we have known for a very long time the importance of maintaining the temperature of the newborn we are still faced with new challenges in the care of the sick immature baby Tem-perature control during their period of adaptation to extrauterine life is often poor and allowing these vulnerable babies to cool is associated with adverse outcome Simple measures can prevent hypothermia following delivery If cold at birth is associated with poor outcome there is no reason to believe that preventing ther-mal stress is any less important once the baby is in the neonatal unit It is important that the risks and benefits associated with various methods of controlling the infantrsquos temperature are fully understood
RefeRenCeS
1 Cone te perspectives in neonatology in Sith gF Vidyasagar D eds
Historical Review and Recent advances in neonatal and perinatal
medicine mead Johnson nutritional Division 1983 p 9ndash33
2 Silverman Wa Fertig JW Berger ap the influence of the thermal
environment upon survival of newly born preterm infants Pediatrics
1958 22 876ndash885
3 Silverman Wa agate FJ Fertig JW a sequential trial of the
nonthermal effect of atmospheric humidity on survival of human
infants of low birth weight Pediatrics 1963 31 710ndash724
8 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
4 Costeloe K Hennessy e gibson at marlow n Wilkinson aR for the
epiCure Study group the epiCure study outcomes to discharge
from hospital for infants born at the threshold of viability Pediatrics
2000 196 659ndash671
5 CeSDi project 2728 available from wwwcemachorguk
publicationsp2728mainreportpdf
6 parry g tucker J tarnow-mordi W for the uK neonatal Staffing
Study Collaborative group CRiB ii an update of the clinical risk
index for babies score Lancet 2003 361 1789ndash1791
7 Richardson DK Corcoran JD escobar gJ et al Snap-ii and Snappe-ii
simplified newborn illness severity and mortality risk scores
J Pediatr 2001 138 92ndash100
8 Wyatt JS gluckman pD liu py et al CoolCap Study group
Determinants of outcomes after head cooling for neonatal
encephalopathy Pediatrics 2007 119 912ndash921
9 yager Jy armstrong ea Jaharus C Saucier Dm Wirrell eC preventing
hyperthermia decreases brain damage following neonatal-ischemic
seizures Brain Res 2004 1011 48ndash57
10 Harned Jr HS Herrington Rt Ferreiro Ji the effects of immersion
and temperature on respiration in newborn lambs Pediatrics 1970
45 598ndash605
11 laptook aR Salhab W Bhaskar B neonatal Research network
admission temperature of low birth weight infants predictors and
associated morbidities Pediatrics 2007 119 e643ndash649
12 lyon aJ pikaar me Badger p mcintosh n temperature control in
infants less than 1000g birthweight in the first 5 days of life Arch
Dis Child 1997 76 F47ndash50
13 Vohra S Roberts RS Zhang B Janes m Schmidt B Heat loss
prevention (Help) in the delivery room a randomized controlled
trial of polyethylene occlusive skin wrapping in very preterm infants
J Pediatr 2004 145 750ndash753
14 lyon aJ Stenson B Cold comfort for babies Arch Dis Child Fetal
Neonatal Ed 2004 89 F93ndash94
15 Stothers JK Head insulation and heat loss in the newborn Arch Dis
Child 1981 56 530ndash534
16 newton t Watkinson m preventing hypothermia at birth in
preterm babies at a cost of overheating some Arch Dis Child Fetal
Neonatal Ed 2003 88 F256
17 Smith Cl Quine D mcCrosson F armstrong l lyon a Stenson B
Changes in body temperature after birth in preterm infants
stabilised in polythene bags Arch Dis Child Fetal Neonatal Ed 2005
90 F444
18 mcCall em alderdice Fa Halliday Hl Jenkins Jg Vohra S
interventions to prevent hypothermia at birth in preterm andor low
birthweight babies Cochrane Database of Systematic Reviews 2005
issue 1 art noCD004210 doi10100214651858CD004210pub2
19 meyer mp Bold gt admission temperatures following radiant
warmer or incubator transport for preterm infants lt 28 weeks
a randomised study Arch Dis Child Fetal Neonatal Ed 2007 92
F295ndash297
20 Carmichael a mcCullough S Kempley St Critical dependence of
acetate thermal mattress on gel activation temperature Arch Dis
Child Fetal Neonatal Ed 2007 92 F44ndash45
21 Hey en the care of babies in incubators in gairdner D Hull D
eds Recent advances in paediatrics 4th edn london J amp a
Churchill 1971 p 171ndash216
22 Whitelaw a Heisterkamp g Sleath K acolet D Richard m Skin-to-
skin contact for very low birthweight infants and their mothers Arch
Dis Child 1988 63 1377ndash1381
paeDiatRiCS anD CHilD HealtH 184 15
23 Bauer K pyper a Sperling p uhrig C Versmold H effects of
gestational and postnatal age on body temperature oxygen
consumption and activity during early skin-to-skin contact between
preterm infants of 25ndash30-week gestation and their mothers Pediatr
Res 1998 44 247ndash251
24 Hey en Katz g orsquoConnell B the total thermal insulation of the
newborn baby J Physiol 1970 207 683ndash689
25 Hey en temperature regulation in sick infants in tinker J Rapin m
eds Care of the Critically ill patient Berlin Springer 1983 p
1013ndash1029
26 leBlanc mH Relative efficacy of an incubator and an open warmer
in producing thermoneutrality for the small premature infant
Pediatrics 1982 69 439ndash445
27 meyer mp payton mJ Salmon a Hutchinson C deKlerk a
a clinical comparison of radiant warmer and incubator care for
preterm infants from birth to 1800grms Pediatrics 2001 108
395ndash401
28 Silverman Wa Blanc Wa effect of humidity on survival of newly
born premature infants Pediatrics 1957 20 477ndash487
29 Hammarlund K Sedin g transepidermal water loss in newborn
infants iii relation to gestational age Acta Paediatr Scand 1979
68 795ndash801
30 Hammerlund K Stroumlmberg B Sedin g Heat loss from the skin of
preterm and fullterm newborn infants during the first weeks after
birth Biol Neonate 1986 50 1ndash10
31 Kalia yn nonata lB lund CH guy RH Development of skin
barrier function in premature infants J Invest Dermatol 1998 111
320ndash326
32 Kjartansson S arsan S Hammarlund K Sjoumlrs g Sedin g Water loss
from the skin of term and preterm infants nursed under a radiant
heater Pediatr Res 1995 37 233ndash238
33 mok Q Bass Ca Ducker Da mcintosh n temperature instability
during nursing procedures in preterm neonates Arch Dis Child
1991 66 783ndash786
34 mancini aJ Sookdeo-Drost S madison KC Smoller BR lane at
Semipermeable dressings improve epidermal barrier function in
premature infants Pediatr Res 1994 36 306ndash314
35 Donahue ml phelps Dl Richter Se Davis Jm a semipermeable skin
dressing for extremely low birth weight infants J Perinatol 1996 16
20ndash26
36 nopper aJ Horii Ka Sookdeo-Drost S Wang tH mancini aJ lane at
topical ointment therapy benefits premature infants J Pediatr 1996
128 660ndash669
37 pabst RC Starr Kp Qaiyumi S Schwalbe RS gewold iH the effect
of application of aquaphor on skin condition fluid requirements
and bacterial colonization in very low birth weight infants
J Perinatol 1999 19 278ndash283
38 Kjartansson S Hammarlund K Sedin g insensible water loss from
the skin during phototherapy in term and preterm infants Acta
Paediatr 1992 81 764ndash768
39 grunhagen DJ de Boer mg de Beaufort aJ Walther FJ
transepidermal water loss during halogen spotlight phototherapy in
preterm infants Pediatr Res 2002 51 402ndash405
40 Hanley K Jiand y elias pm Feingold KR Williams ml acceleration
of barrier ontogenesis in vitro through air exposure Pediatr Res
1997 41 293ndash299
41 Denda m Sato J masuda y et al exposure to a dry environment
enhances epidermal permeability barrier function J Invest Dermatol
1998 111 858ndash863
9 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
42 Aringgren J Sjoumlrs g Sedin g ambient humidity influences the rate of
skin barrier maturation in extremely preterm infants J Pediatr 2006
148 613ndash617
43 Sinclair l Sinn J Higher versus lower humidity for the prevention of
morbidity and mortality in preterm infants in incubators (protocol)
Cochrane Database Syst Rev 2007 issue 2 art noCD006472
doi10100214651858
44 Hey en Katz g the optimum thermal environment for naked
babies Arch Dis Child 1970 45 328ndash334
45 Sauer pJJ Dane HJ Visser HKa new standards for neutral thermal
environment of healthy very low birthweight infants in week one of
life Arch Dis Child 1984 59 18ndash22
46 Dollberg S Xi y Donnelly mm a noninvasive alternative to rectal
thermometry for continuous measurement of core temperature in
the piglet Pediatr Res 1993 34 512ndash517
47 messaritakis J anagnostakis D laskari H Katerelos C Rectal-skin
temperature difference in septicaemic newborn infants Arch Dis
Child 1990 65 380ndash382
paeDiatRiCS anD CHilD HealtH 184 16
Practice points
bull Hypothermia in the newborn infant is associated with adverse
outcome
bull Despite improvements in technology the preterm baby is still
at high risk of hypothermia immediately after delivery
bull prevention of evaporative heat losses eliminates hypothermia
at resuscitation
bull High evaporative fluid losses must be prevented if the baby
is nursed under a radiant heater
bull more studies are needed to determine the optimum
management after delivery and to show if reducing
transepidermal water loss has an effect on the rate of skin
maturation
bull Continuous monitoring and display of a central and peripheral
temperature gives early warning of developing cold stress
0 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemiaJ m Hawdon
Abstractat birth the newborn baby undergoes many adaptive changes to inde-
pendent extrauterine life these include the changes of metabolic adap-
tation which must be understood in order to identify and manage the
conditions in which metabolic adaptation is delayed impaired or fails
resulting in low levels of glucose and other metabolic fuels which in turn
affect neonatal neurological function and if prolonged and severe cause
potential adverse outcome Babies identified as at risk of impaired met-
abolic adaptation must undergo clinical monitoring including accurate
blood glucose monitoring tailored to their condition Babies who present
with abnormal clinical signs in association with a low blood glucose level
must be investigated for underlying cause and treated promptly preven-
tion and treatment of clinically significant hypoglycaemia must be planned
to avoid compromising successful establishment of breast feeding
Keywords alternative fuels blood glucose breast feeding neonatal
metabolic adaptation operational thresholds risk factors
Introduction
At birth the newborn baby undergoes many adaptive changes to independent extrauterine life These include the changes of met-abolic adaptation essential to ensure energy provision to vital organs and then to sustain growth and further development The changes involved in metabolic adaptation must be understood in order to identify and manage the conditions in which metabolic adaptation is delayed impaired or fails The clinical outcome of these circumstances is usually referred to with the single short-hand diagnostic term lsquoneonatal hypoglycaemiarsquo However as will be illustrated in this article it is not appropriate to ascribe a diagnostic label to neonatal hypoglycaemia first because glucose is not the only fuel in the neonatersquos fuel economy and second because hypoglycaemia is the consequence of a number of vari-ous underlying disorders and thus does not in itself warrant a diagnostic label
There have been extensive studies of metabolic adaptation in human neonates and neonatal non-human mammals The latter studies have identified those mammals most similar to humans
J M Hawdon MA MBBS MRCP FRCPCH PhD is Consultant Neonatologist and
Honorary Senior Lecturer at UCL EGA Institute for Womenrsquos Health
Elizabeth Garrett Anderson and Obstetric Hospital University College
London Hospitals NHS Foundation Trust Huntley Street London UK
paeDiatRiCS anD CHilD HealtH 184 161
in terms of metabolic adaptation and sought to compare nutri-tionally comparable time frames eg suckling versus weaning periods Whilst the processes of metabolic adaptation are well described in term and preterm human neonates there are few if any clinical studies in human neonates of sufficient rigour to provide evidence for the circumstances in which brain injury may occur and thus it is not possible to provide evidence-based guide-lines for the prevention and management of clinically significant hypoglycaemia Therefore recommendations in this article and in the referenced review articles by recognized experts remain pragmatic and urge clinicians to individualize management for each baby placing heavy emphasis on careful clinical evaluation rather than single numerical definitions of brain-injuring hypogly-caemia and on detecting and treating underlying pathologies1ndash6
Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
During intrauterine life the fetus receives via the placenta a con-stant supply of nutrients initially for growth but in the third tri-mester also for storage Glucose crosses the healthy placenta at a rate of approximately 5 mgkgmin In addition to that required for basal fetal metabolism glucose is converted to glycogen which is stored in the liver cardiac muscle and central nervous system In the third trimester excess glucose is converted to tri-glycerides which are stored in adipose tissue
Insulin is an important fetal hormone to ensure glucose and other substrates are utilized for growth and storage but in nor-mal circumstances insulin is not required for fetal glucose con-trol The exception is for the infant of the mother with poorly controlled diabetes when transfer of glucose across the placenta is at a higher rate driven by the maternalndashfetal concentration gra-dient This results in increased insulin secretion excess growth and increased storage of glycogen and adipose tissue (macroso-mia) along with increased risk of intracellular hypoxia
Conversely in the fetus affected by severe placental insuffi-ciency transfer of glucose and other nutrients across the placenta is at a lower rate and the fetus is required to metabolize first its own fuel stores and then structural proteins (eg in muscle) to ensure energy delivery to the vital organs assisted by the redis-tribution of blood flow to these organs Should placental function deteriorate further these adaptive responses fail Fetal hypogly-caemia has been described in these circumstances78
When placental nutrition abruptly ceases at birth the healthy neonate is dependent upon endocrine changes to initiate meta-bolic adaptation Insulin levels fall steadily and the action of any residual circulating insulin is overcome by the surge of the coun-ter-regulatory hormones glucagon and the catecholamines This change in the balance of glucoregulatory hormones induces the activity of key enzymes for glycogenolysis (release of glucose from glycogen stores) gluconeogenesis (production of glucose from precursors including glycerol and amino acids) lipolysis (release of free fatty acids and glycerol from adipose tissue stores) and beta-oxidation of fatty acids to produce ketone bodies910 If fasting is prolonged structural protein is broken down to release gluconeogenic amino acids Other than lipolysis and proteolysis all of these processes take place in the liver Glycogenolysis also takes place in cardiac muscle and the central nervous system providing immediate energy (in the form of glucose or lactate)
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
at this crucial time411 Clearly during this catabolic phase of immediate postnatal nutrition prior to the establishment of suck-ling feeds provision of energy for vital organ function is at the expense of growth and fuel storage
The postnatal metabolic transition is characterized by low cir-culating blood glucose concentrations compared to those of older infants and children often for a number of days12 This is almost always of no pathological significance for a number of reasons including differences in the function and metabolic requirements of the brain and importantly the production and utilization of alter-native fuels lactate and ketone bodies which are in plentiful supply in the neonate341213ndash20 An important finding from clinical studies and of clinical relevance to those caring for mothers and babies is that in all groups of infants studied to date those who are breast fed have higher circulating ketone body levels than those who are formula fed even after correcting for blood glucose levels102122
There are circumstances however when hypoglycaemia is severe and prolonged and conditions when alternative fuel pro-duction is also impaired or fails In these circumstances low blood glucose levels do acquire clinical significance The key metabolic processes and the risk factors for impaired metabolic adaptation are summarized in Table 1
Metabolic changes at birth ndash key hormones and metabolic processes and risk factors for impaired metabolic adaptation
Postnatal metabolic
changes
Risk factors
Hormones
insulin falls neonatal hyperinsulinism ndash infant of
diabetic mother or idiopathic
glucagon surge possibly blunted by iv glucose or
formula feeds
Catecholamine surge maternal beta-blocker medication
(Cortisol ndash weak effect) (pituitary or adrenal insufficiency)
Metabolic processes
glygogenolysis preterm intrauterine growth
restriction (iugR) ndash reduced stores
perinatal hypoxia-ischaemia ndash stores
utilized
Hyperinsulinism
maternal beta-blocker medication
glycogen storage disorders
gluconeogenesis Hyperinsulinism
maternal beta-blocker medication
Hepatic dysfunction
Very rare inborn errors of metabolism
lipolysis preterm iugR ndash reduced stores
Hyperinsulinism
maternal beta-blocker medication
Ketogenesis Defects of beta-oxidation of fatty
acids
Hepatic dysfunction
Table 1
paeDiatRiCS anD CHilD HealtH 184 16
Impaired metabolic adaptation
Risk factors for impaired metabolic adaptation vary and may be related to any of the following reduced body fuel stores failure of the normal endocrine changes at birth systemic illnesses which impede function of the liver where the key metabolic processes occur or rarely inborn errors of metabolism (see Table 1)
It is well recognized that significant hypoglycaemia will result in a reduced level of consciousness andor fits However it is always important to be alert for detect and treat an underlying pathology which could be causing both the hypoglycaemia and the abnormal signs Often abnormal signs and hypoglycaemia are co-morbidities eg a primary neurological problem causes both abnormal neurological signs and hypoglycaemia secondary to poor feeding For this reason all possible underlying causes for presentation with hypoglycaemia must be considered and investigations planned accordingly Investigations for inborn errors of metabolism and endocrine disorders are most informa-tive if carried out when blood glucose levels are low
There have been extensive efforts to use data from clinical stud-ies of the human neonate to determine the significance of neonatal hypoglycaemia in terms of neurophysiological neurodevelopmental and neuroradiological sequelae However there are major difficul-ties in interpreting these clinical studies as to date these have been flawed by confounding factors such as immaturity placental insuf-ficiency and co-existing complications by heterogeneity of subjects and by failure to take into account protective mechanisms11423 The evidence from both animal and human studies suggests lsquopurersquo hypo-glycaemic brain injury is rare and for hypoglycaemic brain injury to occur there must be co-existing failure of metabolic adaptation such that alternative fuels are not available There is no evidence that lsquotransitionalrsquo hypoglycaemia in the healthy neonate is associated with acute or long term sequelae and indeed even for babies in the at-risk groups on many occasions protective factors will prevail
Diagnosis of clinically significant hypoglycaemia
lsquoNeonatal hypoglycaemiarsquo is a commonly cited diagnosis most often based on a single blood glucose level and using inaccurate methods of measurement and with disregard for the presence or absence of associated clinical signs In the many published texts and local guidelines there is no consistency of approach For this reason a multinational group of experts attempted to examine critically the evidence on which clinical recommendations should be made1 Fol-lowing detailed analysis the authors considered it impossible to define hypoglycaemia as a single blood glucose level and instead suggested operational thresholds and therapeutic goals They con-cluded that low blood glucose levels accompanied by neurological signs should be investigated and treated regardless of the blood glu-cose level They also pragmatically concluded that a blood glucose level below 10 mmollitre should be treated immediately In babies who are at risk of impaired metabolic adaptation but who have no clinical signs it is recommended that interventions to raise blood glucose level are considered if blood glucose levels are persistently below 20 mmollitre For sick and very low birthweight babies who are likely to have a requirement for intravenous glucose there should be a lsquotherapeutic goalrsquo to maintain blood glucose levels above 25 mmollitre Where there is known hyperinsulinism (a very high-risk condition characterized by high intravenous glucose
2 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
requirements to maintain normoglycaemia) an operational thresh-old and therapeutic goal of 35 mmollitre has been proposed24
Finally there must be careful consideration of the infant of the diabetic mother In extreme and rare cases there may be signifi-cant but transient hyperinsulinism and in these cases the thera-peutic goal must be 35 mmollitre More commonly babies whose mothersrsquo diabetes has been well controlled will have normal lsquotran-sitional hypoglycaemiarsquo or slightly delayed metabolic adaptation while insulin levels fall postnatally There must be careful and repeated clinical assessment including blood glucose monitoring For infants of diabetic mothers who have no evidence of signifi-cant hyperinsulinism and no abnormal clinical signs there is no evidence that the operational threshold for hyperinsulinism must be applied Indeed to do so would result in separation of large numbers of healthy babies from their mothers with the conse-quent impact upon breast feeding and resource allocation25
The operational thresholds for various groups of babies are summarized in Table 2
The guidance relating to operational thresholds is predicated upon the accurate measurement of blood glucose levels It is now well known that the commonly used reagent strips are insufficiently accurate to diagnose hypoglycaemia and monitor at-risk infants and there must be access to equipment which allows immediate and accurate determination of blood glucose levels1426ndash28
Blood glucose monitoring
An accurate method for blood glucose monitoring must be employed as described above The sample should be free flowing venous or from a warm heel such that the blood flows freely without squeezing
Blood of high haematocrit often yields low blood glucose lev-els because of dilution of glucose by red cell water However this is also clinically relevant because polycythaemia is itself a high-risk situation Therefore in polycythaemic infants both the haematocrit and blood glucose level must be monitored and both acted upon accordingly
Operational thresholds for blood glucose levels in the management of babies at risk of impaired metabolic adaptation124
Clinical condition Blood glucose level at which
to consider intervention and
therapeutic goal
all at-risk babies lt10 mmollitre
abnormal neurological
signs
intervene regardless of blood
glucose levelSystematically unwell baby therapeutic goal of 25 mmollitre
at-risk babies no abnormal
neurological signs
persistently lt20 mmollitre
Hyperinsulinism 35 mmollitre
Table 2
paeDiatRiCS anD CHilD HealtH 184 163
Only babies in at-risk groups or babies who have abnormal neurological signs should be subjected to blood glucose monitor-ing (Table 3)
It is important not to commence blood glucose monitoring too soon after birth as to do so would fail to differentiate the baby with incipient hypoglycaemia from the baby undergoing the nor-mal postnatal fall in blood glucose level It is recommended in the otherwise healthy but at-risk baby to wait until around 3 h after birth to make the first blood glucose estimation2528 In prac-tice this is usually before the second feed assuming best practice of offering a baby a breast (or if necessary formula feed) imme-diately after birth Clearly if the baby is unwell or has abnormal clinical signs in the first 3 h they will be treated according to clinical condition which will include intravenous fluids and the therapeutic goal described above would apply
Similarly the temptation to measure blood glucose level shortly (within 2 h) after intravenous glucose has been discon-tinued must be avoided In this circumstance as at birth blood glucose levels fall and then subsequently rise in response to coun-ter-regulation It is this effective rise which must be assessed by blood glucose measurement at least 2 h after a change is made (provided the baby remains clinically well)
Blood glucose levels rise after a feed and fall to a nadir before the subsequent feed As our concern is the lowest blood glucose level during the feed cycle and as this measurement may assist in determining best feed frequency it is important that pre-feed blood glucose concentration is measured There is no clinical value in measuring a post-feed blood glucose level as this may be falsely reassuring and this practice subjects babies to more frequent heel pricks or venesections than is necessary
Finally consideration must be given to when to discontinue blood glucose monitoring This will depend upon the babyrsquos clin-ical condition feeding pattern and underlying disorder or risk factors for impaired metabolic adaptation
Prevention and management of clinically significant hypoglycaemia
In babies at risk of clinically significant hypoglycaemia and who are well enough to tolerate enteral feeds milk feeds are the
At-risk babies for whom blood glucose monitoring is recommended
abnormal neurological signs
Systemically unwell eg suspected or proven infection
hypoxicndashischaemic encephalopathy
preterm (lt 37 weeks)
intrauterine growth restriction (lt 2nd centile and any baby with
signs of wasting)
infant of diabetic mother
polycythaemia
maternal beta-blocker medication
Suspected hyperinsulinism
Suspected inborn error of metabolism or endocrine disorder
Table 3
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
mainstay of prevention For babies who are able to feed orally breast feeding should be first choice and there must be maximal support for the mother to do so This is a key clinical priority for midwives and paediatricians
If there are concerns regarding adequacy of breast feeding to prevent hypoglycaemia the mother should be encouraged to commence expression of milk from very soon after birth If there is insufficient breast milk to prevent babies reaching the opera-tional thresholds described above there should be judicious use of formula milk using only the smallest amount required to keep the babyrsquos glucose in the required range Formula milk in exces-sive quantities has been demonstrated to suppress normal meta-bolic adaptation2122
In babies for whom early enteral feeds are not appropriate or not tolerated or for whom enteral feeding does not prevent blood glucose level falling below operational thresholds intravenous glucose infusion at rates around 4ndash5 mgkgmin (58ndash72 mlkgd of 10 dextrose) are usually sufficient to prevent hypoglycae-mia If blood glucose levels remain below therapeutic goals the rate of infusion may be steadily increased Excess glucose infu-sion over and above that required to maintain the therapeutic goal will stimulate insulin and there is a risk of rebound hypo-glycaemia if high rate glucose infusions are too rapidly reduced Milk feeds if tolerated should be continued if intravenous glu-cose is commenced
If infused volume of glucose solution becomes excessive in order to maintain therapeutic goals or if fluid restriction must be applied more concentrated glucose concentrations must be infused through a central venous line This is particularly rel-evant to the hyperinsulinaemic baby in whom glucose infusion rates in excess of 8ndash10 mgkgmin are required to maintain ther-apeutic goals There is a high risk of severe and brain-damaging hypoglycaemia if treatment is delayed or fails to raise blood glu-cose levels and management of these babies requires consulta-tion with or referral to a specialist centre24
If there is presentation of hypoglycaemia with abnormal clinical signs or a very low blood glucose level (less than 1 mmollitre) this mandates urgent treatment with intravenous glucose The rates of glucose infusion described above are usually sufficient to bring the blood glucose level rapidly to the therapeutic goal without a bolus of glucose being necessary In fact a bolus dose of glucose will result in a peak blood glucose level and then an insulin surge making subsequent management problematical This is minimized by the use of a lsquomini-bolusrsquo should a bolus of glucose be required ndash 200 mg glucosekg (2 mlkg of 10 dextrose)28 Indications for mini-bolus are infants presenting with fits or coma or an lsquounre-cordablersquo or zero blood glucose level A mini-bolus should always be followed with glucose infusion or an increased glucose infusion rate if a baby already receiving intravenous glucose has required a mini-bolus
The temptation to supplement enteral feeds with glucose polymers and energy supplements (eg Duocal) or to use oral glucose gels or solutions (eg Hypostop) should be avoided as this carries a risk of necrotizing enterocolitis is likely to suppress normal metabolic adaptation and will suppress the appetite of the baby for effective oral feeding
Finally there are additional medications which may be employed in specific circumstances (Table 4) More detailed descriptions are given elsewhere242728 Babies who have hypoglycaemia which
paeDiatRiCS anD CHilD HealtH 184 164
is difficult to control by the measures described above and who require these additional treatments should be cared for in a centre which has expertise in metabolic and endocrinological conditions
Summary
Much controversy and confusion has surrounded neonatal hypo-glycaemia but this usually arises as a result of failure to under-stand the processes of normal metabolic adaptation and the fact that hypoglycaemia is a presenting sign rather than a diagnosis in itself Plans for investigation and management must be based upon the most likely underlying cause of impaired metabolic adaptation and take into account the clinical condition of the baby This is counter to the current trend to propose rigid pro-tocols and algorithms and re-introduces the value of detailed clinical evaluation and decision making The mainstay of man-agement is close clinical observation of vulnerable infants and energy provision tailored to their individual needs whilst avoid-ing excessively invasive management (namely unnecessary sep-aration of mother and baby routine or excessive formula milk supplementation or intravenous glucose administration) which themselves inhibit protective metabolic responses and impede successful establishment of breast feeding
ReFeRenCeS
1 Cornblath m Hawdon Jm Williams aF et al Controversies regarding
definition of neonatal hypoglycemia Suggested operational
thresholds Pediatrics 2000 105 1141ndash1145
2 Cornblath m ichord R Hypoglycemia in the neonate Semin
Perinatol 2000 24 136ndash149
3 Vannucci RC Vannucci SJ Hypoglycaemic brain injury Semin
Neonatol 2001 6 147ndash155
4 Rozance pJ Hay WW Hypoglycaemia in newborn infants features
associated with adverse outcomes Biol Neonate 2006 90 74ndash86
5 Hawdon Jm Hypoglycaemia in newborn infants defining the
features associated with adverse outcomes ndash a challenging remit
Biol Neonate 2006 90 87ndash88
6 Williams aF neonatal hypoglycaemia clinical and legal aspects
Semin Fetal Neonatal Med 2005 10 363ndash368
7 Soothill pW nicolaides KH Campbell S prenatal asphyxia
hyperlacticaemia hypoglycaemia and erythroblastosis in growth
retarded fetuses BMJ 1987 294 1051ndash1053
Additional medication in specific conditions (if these are required there must also be referral to a specialist centre)
Medication Indication
glucagon intramuscular bolus dose of 200 μgkg
transient rise in blood glucose level eg
when difficulty re-siting intravenous infusion
Diazoxide Hyperinsulinism
Hydorcortisone pituitary or adrenal insufficiency
Table 4
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
8 Hawdon Jm Ward platt mp mcphail S Cameron H Walkinshaw Sa
prediction of impaired metabolic adaptation by antenatal Doppler
studies in small for gestational age fetuses Arch Dis Child 1992
67 787ndash792
9 Deshpande S Hawdon Jm et al adaptation to extrauterine life in
Rodeck C Whittle m eds Fetal medicine Basic Science and Clinical
practice edinburgh Churchill livingstone 1999
10 Ward platt m Deshpande S metabolic adaptation at birth Semin
Fetal Neonatal Med 2005 10 341ndash350
11 eyre Ja Stuart ag Forsyth RJ Heaviside D Bartlett K glucose
export from the brain in man evidence for a role for astrocytic
glycogen as a reservoir of glucose for neural metabolism Brain Res
1994 28 349ndash352
12 Hawdon Jm Ward platt mp aynsley-green a patterns of metabolic
adaptation for preterm and term infants in the first neonatal week
Arch Dis Child 1992 67 357ndash365
13 Hawdon Jm Ward platt mp aynsley-green a prevention and
management of neonatal hypoglycaemia Arch Dis Child Fetal
Neonatal Ed 1994 70 F60ndash64
14 Hawdon Jm Hypoglycaemia and the neonatal brain Eur J Paediatr
1999 158 S9ndash12
15 massieu l Haces ml montiel t Hernaacutendez-Fonseca K acetoacetate
protects hippocampal neurons against glutamate-mediated neuronal
damage during glycolysis inhibition Neuroscience 2003 120
365ndash378
16 yamada Ka Rensing n thio ll Ketogenic diet reduces
hypoglycaemia-induced neuronal death in young rats Neurosci Lett
2005 385 210ndash214
17 nehlig a Brain uptake and metabolism of ketone bodies in animal
models Prostaglandins Leukot Essent Fatty Acids 2004 70
265ndash275
18 Hernaacutendez mJ Vannucci RC Salcedo a Brennan RW Cerebral blood
flow and metabolism during hypoglycemia in newborn dogs
J Neurochem 1980 35 622ndash628
19 Vannucci RC nardis ee Vannucci SJ Campbell pa Cerebral
carbohydrate and energy metabolism during hypoglycaemia in
newborn dogs Am J Physiol 1981 256 H1659ndashH1666
20 anwar m Vannucci RC autoradiographic determination of regional
cerebral blood flow during hypoglycaemia in newborn dogs Pediatr
Res 1988 24 41ndash45
21 Hawdon Jm Williams aF et al Formula supplements given to
healthy breastfed preterm babies inhibit postnatal metabolic
adaptation results of a randomised controlled trial Arch Dis Child
2000 82 a30
paeDiatRiCS anD CHilD HealtH 184 16
22 de Rooy l Hawdon Jm nutritional factors that affect the postnatal
metabolic adaptation of full-term small- and large-for gestational
age infants Pediatrics 2002 109 e42
23 Hawdon Jm Hypoglycaemia and brain injury ndash when neonatal
metabolic adaptation fails in levene m ed Fetal and neonatal
neurology and neurosurgery edinburgh Churchill livingstone in
press
24 Hussain K Congenital hyperinsulinism Semin Fetal Neonatal Med
2005 10 369ndash376
25 acolet D Diabetes in pregnancy Caring for the Baby after Birth
CemaCH 2007 2
26 Hussain K Sharief n the inaccuracy of venous and capillary blood
glucose measurement using reagent strips in the newborn period
and the effect of haematocrit Early Hum Dev 2000 57 111ndash121
27 Hawdon Jm Disorders of blood glucose homeostasis in the neonate
in Rennie Jm ed Robertonrsquos textbook of neonatology 4th edn
edinburgh Churchill livingstone 2005
28 Deshpande S Ward platt mp the investigation and management
of neonatal hypoglycaemia Semin Fetal Neonatal Med 2005 10
351ndash361
Practice points
bull identify risk factors for impaired metabolic adaptation
bull Clinical monitoring including accurate blood glucose
measurement for at-risk babies
bull Feed at-risk babies soon after birth and maintain thermal
homeostasis
bull take first blood glucose level at 3ndash4 h of age
bull intervene in at-risk baby with no clinical signs if two
consecutive blood glucose measurements lt 20 mmollitre
bull intervene in any baby with blood glucose measurement
lt 10 mmollitre
bull intervene in any baby with abnormal clinical signs regardless
of blood glucose level
bull investigate for underlying cause of failure of metabolic
adaptation
bull maintain lactation and breast feeding
5 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Resuscitation of the term and premature babyJonathan Wyllie
Abstractalthough most newly born babies establish normal respiration and
circulation without help up to 1minus2 may require some resuscitation
or stabilization Babies who do not establish adequate regular normal
breathing or who have a heart rate of less than 100 beatsmin or other
problems such as prematurity may require assistance the differences in
approach to the resuscitation of such babies originate in the physiology
and pathophysiology of acute asphyxia at birth However management
of airway and breathing remain the key features of resuscitation and
where cardiac depression has occurred this is nearly always due to hy-
poxia secondary to respiratory compromise therefore most babies will
respond within 2minus3 min of effective aeration of the lungs and the need
for intubation chest compressions or drugs is rare the international
liaison Committee on Resuscitation (ilCoR) evaluated evidence in 2000
and 2005 in order to provide guidelines for resuscitation they will do
so again for 2010 this evidence is limited in terms of both quantity and
quality and controversies still exist more research is needed to ensure
that our future actions are based upon evidence rather than history this
article will review the recommended approach to resuscitation as well as
some newer evidence
Keywords guidelines neonatal newborn premature resuscitation
Background
In the UK 669 601 babies were born alive in 2006 and most made the transition to extrauterine life without problems Those babies who did not establish adequate regular normal breathing or who had a heart rate of less than 100 beatsmin may have required assistance1 Factual evidence concerning the true requirement for resuscitation at birth is sparse Up to 10 of newborns may require some assistance to begin breathing with less than 1 needing extensive resuscitation2 However just because a baby received resuscitation does not necessarily mean that it was required and rates of intervention may be altered by educa-tion34 or the personnel present at deliveries5 In a UK tertiary centre with a standard approach to resuscitation at birth up to 12 of all babies received some airway assistance with just over 1 being intubated3 In Sweden only 1 of babies over 2500 g required mask or endotracheal tube ventilation at birth of which most responded to the former4
Jonathan Wyllie MBChB FRCPCH is Consultant Neonatologist at the James
Cook University Hospital Marton Road Middlesbrough TS4 3BW UK
paeDiatRiCS anD CHilD HealtH 184 16
Sometimes it is possible to predict babies who are likely to have respiratory depression at birth and to have appropriate per-sonnel present at delivery Guidelines for attendance at deliveries will vary with institution but even when almost 40 of deliv-eries are attended there may still be a further 15 of babies who require unexpected resuscitation5 a proportion that seems to remain whatever changes are made
The physiology of babies requiring help at birth has been summarized previously167 It allows a logical approach to resus-citation (Figure 1) when evidence is lacking and may prompt further research
Resuscitation at birth
PreparationAt birth resuscitation is more likely in babies with intrapartum evidence of significant fetal compromise those less than 35 weeksrsquo gestation those delivering vaginally by the breech and in multiple births Personnel trained in newborn resuscitation should be available at every delivery1 Someone experienced in tracheal intubation and advanced resuscitation should also be easily available for normal low-risk deliveries in hospital and ideally in attendance for deliveries with an increased likelihood of needing resuscitation In the latter cases the equipment and environment can be prepared beforehand including a discussion with the parents Wash your hands put on gloves and consider what help may be needed
Cord clampingAt birth it has long been known that delay in clamping the cord will lead to less anaemia in babies and reduce subsequent iron deficiency8 However few hospitals have practised this interven-tion due to worries about hypothermia and the need to resusci-tate or stabilize babies In developed countries the advantages seemed to be outweighed by the potential disadvantages A recent randomized controlled study of delayed clamping of the cord in premature babies found that the intervention group had less late-onset sepsis and fewer intraventricular haemorrhages9 This is a low-risk strategy which needs further evaluation in order to introduce it without increasing other risk factors in pre-mature deliveries
Assessment and temperature controlAssessment and temperature control for the newborn baby should occur at all deliveries The assessment indicates the need for resuscitation Babies may vary from 23 to 40+ weeksrsquo ges-tation and in weight from 500 to 5000 g They are born naked and wet and if left cannot cope with an environmental tem-perature of less than 32degC However if the term baby is imme-diately dried put skin-to-skin with the mother and covered the delivery room temperature can be as low as 25ndash28degC Obviously the smaller the baby the greater the surface area to mass ratio and the greater the risk of hypothermia Compromised babies are particularly vulnerable10 and hypothermia will lower oxygen tension11 increase metabolic acidosis12 and inhibit surfactant production13
An effective method of maintaining the temperature of prema-ture babies less than 28 weeksrsquo gestation is wrapping them with plastic before drying and then placing them under a radiant
6 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Dry the babyRemove any wet towels and cover
Start the clock or note the time
Give 5 inflation breathsLook for a response
If no increase in heart rate look for chest movement
Re-check head positionApply Jaw thrust
Repeat inflation breathsLook for a response
If no increase in heart rate look for chest movement
Try alternative airway opening manoeuvresRepeat inflation breaths
Look for a response
If no increase in heart rate look for chest movement
If the heart rate is not detectable or slow (lt60)Start compressions
3 compressions to each breath
Reassess heart rate every 30 secondsConsider venous access and drugs
Assess colour tone breathing and heart rate
Open the airway
If not breathing
If still not breathing
If no response
If still no response
When the chest is moving
If meconium present
Baby breathing wellDo not suction the airway
Baby floppy and not breathing wellConsider inspection and suction before
inflation breaths
Head in neutral position
Inflation breathsUse a well-fitting face mask
connedted to a
pressure-limited gas supply
Each breath 2ndash3 seconds
duration at 30 cm H2O for a
term baby
Get help from a second personto support the airway andor
inspect the oropharynx under
direct vision and consider
suction andor insert an
oropharyngeal airway
Chest compressionsCompvent ratio 31
Rate 120 events per minute
Ensure the chest moves with each ventilation breath
If breathingReassess heart rate and monitor baby
If heart rate is satisfactory but increasingContinue ventilation breaths at about 30 per
minute until baby is breathing adequately
If heart rate is satisfactory but increasingContinue ventilation breaths at about 30 per
minute until baby is breathing adequately
If heart rate is increasingStop compressions
Continue ventilation breaths at about 30 per
minute until baby is breathing adequately
If the chest is not movingRecheck head position and repeat inflation
breaths If competent consider intubation
If the chest is still not movingThe airway is the problem
Figure 1 newborn life support (Courtesy of the Resuscitation Council uK)
heater14 There is a small risk of hyperthermia so the temperature must be monitored carefully
An assessment is made of the babyrsquos colour tone respira-tions and heart rate127 The most important of these is heart rate and a stethoscope is more reliable than cord pulsation15 How-ever saturation monitors may offer a more reliable assessment of both heart rate and colour16 but their interpretation requires a detailed knowledge of normal saturations at birth at differing gestations A baby who is apnoeic and floppy in the absence of neurological disease is unconscious and likely to be in terminal apnoea however this does not change the initial approach other
paeDiatRiCS anD CHilD HealtH 184 167
than the need to summon help early APGAR scores are never calculated to guide resuscitation
Airway
If a baby is in primary apnoea then with an open airway the first gasp will start to aerate the lungs and most babies will be able to lsquoresuscitatersquo themselves as shown in physiological stud-ies on animals Neutral positioning of the babyrsquos head chin lift jaw thrust oropharyngeal airways and endotracheal intubation may all be helpful in certain situations if performed correctly17
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Endotracheal intubationThe placement of an endotracheal tube has long been the gold standard of airway control and this remains true in the unconscious baby if it is correctly sized placed and fixed in a timely manner However experience is directly related to effec-tiveness in endotracheal intubation1819 and the success rate of less experienced clinicians such as a resident (STA1-3) or a fel-low (STA3-5) is lower varying between 33 and 68 Even senior neonatologists often take longer than guidelines recom-mend19 Experienced clinicians may judge correct endotracheal position visually or by an increase in heart rate with the first breaths but detection of exhaled carbon dioxide will give more rapid confirmation in larger babies12171920 and this can be par-ticularly useful for less experienced clinicians or those supervis-ing them However not all systems for the detection of exhaled carbon dioxide work in the smallest premature infants
Laryngeal masksLaryngeal masks may be effective for ventilating term newborn babies but there are few data for small premature infants There have been reports of dislodged laryngeal airways during paedi-atric arrests when chest compressions have been administered Although success of placement at first attempt by paediatri-cians is greater with a laryngeal mask than with an endotra-cheal tube21 the only and small randomized controlled trial in the delivery room favoured endotracheal intubation when per-formed by an anaesthetist22 Based mainly upon case reports the laryngeal mask can be recommended when positioning and mask ventilation and endotracheal intubation have failed to secure the airway but not as yet as a primary method of airway control
MeconiumIn 2000 Wisewell et al23 reported a large randomized controlled trial showing that tracheal intubation and suctioning of meco-nium-stained but vigorous babies at birth did not reduce the incidence or severity of meconium aspiration syndrome More recently another randomized trial has now shown that suction-ing on the perineum similarly offers no benefit24 Neither of these practices is recommended but intubation and suction of meconium from the trachea of non-vigorous babies born through meconium-stained liquor is still recommended
Breathing
In the apnoeic baby the first breaths establish the resting lung volume and aerate the fluid-filled alveoli This mechanical effect aided by surface tension within the alveoli causes the initial fall in pulmonary vascular resistance Experimentally this effect occurs even if the lungs are ventilated with nitrogen but is increased when air is used presumably due to the vasodilator effect of 21 oxygen The mechanical stretching of the lung also triggers the activation of cyclo-oxygenase beginning the production of prostacyclin Bradykinin is produced which has a further direct vasodilator effect and also possibly via prostacyclin Therefore adequate airway control and passive ventilation is vital not only because babies requiring resuscitation at birth have an almost uniformly respiratory aetiology but also in order to promote post-natal adaptation and reverse any maladaptation
paeDiatRiCS anD CHilD HealtH 184 16
In term babies peak ventilatory pressures of 20ndash30 cmH2O may be required but the minimal pressure needed to achieve an improvement in heart rate should be used or if there is no response chest wall movement Longer breaths at lower pressure may be more effective in displacing alveolar fluid and establish-ing the resting lung volume in lungs with sufficient surfactant and may improve initial oxygenation However premature new-borns are obviously physiologically and anatomically less pre-pared for delivery than infants at term Over-inflation has been implicated in histological lung damage in animal models and high tidal volumes appear to be equally damaging whether given before or immediately after administration of surfactant How-ever the same effect is not seen if these excessive tidal volumes are delivered 15 min after administration of surfactant2526 It is now thought that both excess end expiratory volume and inad-equate end-expiratory volume may cause lung damage2728 In premature infants it would therefore seem sensible to use lower pressures of 20ndash25 cmH2O12 delivered in a controlled way to prevent over-inflation and to apply positive end-expiratory pres-sure (PEEP) to prevent damage from under-inflation PEEP also improves both lung compliance and gas exchange2930 Without PEEP the airways collapse during the expiratory phase in animal models of newborn resuscitation
If animal data can be extrapolated it would also seem appro-priate to give surfactant as soon as possible to premature babies in order to ameliorate damage2526
The majority of newborn infants requiring resuscitation will re-establish regular respiration after administration of a few breaths which may be due to Headrsquos paradoxical reflex by which the inflation triggers an inspiratory effort
VentilationOnce the lungs are aerated if the newborn remains apnoeic ventilation should be continued at 30ndash60 breathsmin avoiding hyperventilation and using the minimum pressure possible to maintain a heart rate greater than 100 beatsmin
Face mask the majority of infants who require ventilation receive it via a face mask This may be attached to a bagvalve system with a spring lsquoblow offrsquo system or a lsquoT-piecersquo with a set flow and pressure It is important to realize that the bagvalve system is flow sensitive and that the harder the operator presses the greater the flow and the higher the delivered pressure In fact 60 cmH2O can be achieved with vigorous squeezing of a self-inflating bag Therefore it may be advantageous that most opera-tors are unlikely to be as effective as they suppose in creating a seal with the mask31 This is a skill that requires tuition and prac-tice31 In delivering a set pressure T-piece systems such as the Tom Thumbcopy or Neopuffcopy perform better than any bagminusvalve system but require a gas supply There is no evidence that lung compliance can be assessed using any bag system
Continuous airway pressure case series have suggested that early or delivery room use of continuous positive airway pres-sure (CPAP) in premature babies may reduce chronic lung dis-ease There have been two randomized trials of which one was a pilot study The data from the COIN trial do not show any advan-tage other than a reduction in intubation and surfactant use in the intervention group However an excess of pneumothorax
8 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
was also reported The Vermont Oxford Network and the SUP-PORT trials will provide further data but at present the delivery room use of CPAP cannot be widely recommended and should be limited to those units experienced in its use or taking part in research
Air or oxygen oxygen has been in widespread use for resuscita-tion at birth since the 1930s and even hyperbaric oxygen was seriously supported in the 1960s For many years there have been concerns about tissue damage from oxygen deprivation during and after resuscitation It became evident in the 1950s that unrestricted oxygen therapy could have serious conse-quences for future vision More recently concerns have been raised about potential adverse effects on respiratory physiology cerebral circulation and tissue damage from oxygen free radicals even during resuscitation A meta-analysis of four human studies demonstrated a reduction in mortality and no evidence of harm in infants resuscitated in air versus 100 oxygen3233 However there are several significant methodological concerns with these studies and the results should be interpreted with caution There is insufficient evidence to recommend any specific concentration of oxygen to be used for newborn resuscitation Monitoring the oxygen saturation of babies may be helpful but as yet there are no time-related normal target ranges and healthy term babies may take up to 10 min to achieve preductal oxygen saturation of greater than 95 and up to 60 min to achieve this postductally
There is therefore equipoise which would be open to an appropriate randomized controlled trial In the meantime the evidence only supports use of either 21 or 100 oxygen It is provoking to realize that if air had been in constant use since the 1930s there would be insufficient evidence for use of supple-mental oxygen
Circulation
Early resuscitation (temperature control airway breathing) provides oxygenated blood in the pulmonary arterioles which if returned to the heart causes the rate to increase34 If due to acidosis and hypoxia the circulation is ineffective then chest compressions may be needed They should be commenced when the heart rate remains below 60min despite effective airway and breathing management127 The best technique is using two hands to encircle the chest1 A ratio of three compressions to one breath is internationally accepted127 but has no evidence to support it Research has shown that neither compressions nor drugs will work in this situation without oxygenated blood so effective lung aeration and ventilation is essential A logical approach would be to fill the alveoli with air and to compress the chest until they are empty However training and teamwork require an agreed ratio which has therefore not changed since guidelines were first agreed internationally Success is assessed by an increase in heart rate which should therefore be assessed every 30 s Compressions stop when the spontaneous heart rate is greater than 60 beatsmin
In hypoxic newborn animal models successful resuscitation can restore cardiac output and blood pressure to levels above baseline within 5ndash10 min However it should be noted that there is a decline to 30 lower than basal levels within 2 h and that blood pressure is relatively spared suggesting an even greater
paeDiatRiCS anD CHilD HealtH 184 16
reduction in tissue perfusion This should be considered in the later care of any neonate who was hypoxic at birth
Drugs
Neonatal bradycardia at birth is almost always due to hypoxia plusmn acidosis and therefore drugs are rarely needed Adrenaline (epi-nephrine) is reported as being used in between 1 and 4 babies per 2000 births which is a large variation in practice Reported success is also variable and must be interpreted in light of this variation The use of drugs in extremely premature infants is con-troversial Some data suggested good outcomes for babies below 28 weeksrsquo gestation given adrenaline but these were flawed by high numbers of babies receiving resuscitative drugs some before the airway had been appropriately managed Audit data now suggest a poor outcome such that many clinicians would now council against the use of adrenaline and other drugs to resuscitate extremely premature newborn babies
Adrenaline (epinephrine)In 2003 a Cochrane review of randomized controlled trials involv-ing adrenaline use for resuscitation of neonates was unable to identify a single clinical trial35 Despite the lack of human neo-natal data animal models show the potential of adrenaline in asphyxial cardiac arrest and it is reasonable to use it when ade-quate ventilation and chest compressions have failed to increase the heart rate above 60 beatsmin Use 10ndash30 μgkg intrave-nously and preferably via an umbilical venous line The tracheal route cannot be recommended but if used it is likely that doses within this range will be ineffective and 100 μgkg might be tried However the safety of such doses has not been studied
BicarbonateThe use of bicarbonate has long been controversial but many of the concerns relate to the rapid correction of acidosis in neonates after resuscitation or the routine use of bicarbonate infusion nei-ther of which can be advocated There are no published human neonatal data to support its use although some exist from animal studies Animal data have also shown that the binding of adren-aline to receptors in the myocardium is significantly impaired by lactic acidosis and recent work on human lymphocyte beta-adrenergic receptors supports this view Whether this is also true of the more important alpha receptors is unknown In practice reversing intracardiac acidosis may improve myocardial function and assist in achieving a return of spontaneous circulation 1ndash2 mmolkg of bicarbonate may be given but this remains a contro-versial area
VolumeVolume expansion should only be given when it is suspected that the baby has suffered blood loss or the infant appears to be in shock (pale poor perfusion weak pulse) and has not responded adequately to other resuscitative measures If there is no history suggestive of blood loss shock is most likely to be due to myo-cardial dysfunction in which case fluids should be administered cautiously The most logical replacement fluid would be blood but in its absence isotonic crystalloid rather than albumin is the solution of choice given in 10 mlkg aliquots and observing the response Three randomized trials in neonates have shown
9 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
isotonic crystalloid to be as effective as albumin for the treat-ment of hypotension but none has examined either the relative or actual effectiveness in resuscitation A recent blinded randomized study comparing normal saline albumin or no volume expansion in a normovolaemic asphyxiated neonatal animal model showed that volume expansion was not beneficial and made a number of parameters worse36
NaloxoneNaloxone is not recommended as part of the initial resuscita-tion of newborns with respiratory depression Before it is given supporting ventilation should have restored the heart rate and colour The dose is 100 μgkg intravenously or intramuscularly Tracheal administration cannot be recommended Although administration of naloxone to neonates who have been exposed to maternal opioids during labour is a practice of long-standing it lacks the proper evidence of efficacy
Non-response to resuscitation
There are few more frightening situations professionally than applying the correct interventions in resuscitating or stabilizing a baby and getting no response Each stage must be adequately performed before moving onto the next and this requires regular reassessment When experienced help is needed at a newborn resuscitation it is usually the airway and ventilation that require correction If the heart rate does not increase this usually means that the lungs have not been successfully aerated In some cases however it may mean that the heart cannot respond as the cir-culation is inadequate In this situation the only way to check that the lungs have been successfully aerated is to see the chest move with ventilation or to obtain evidence of ventilation from a detector of exhaled carbon dioxide If you do not see chest movement after another five breaths the most likely cause is an obstructed airway either due to incorrect positioning or because the jaw has not been drawn forwards An oropharyngeal airway can be very helpful at this point especially in the term baby Only very occasionally is the airway blocked by mucus vernix blood or meconium but if the airway is guaranteed and there is no heart rate response or chest movement this should be sought by direct suction of the trachea even in the absence of any meconium staining of liquor Pneumothoraces can occur spontaneously after delivery but are rare at resuscitation carried out with pressure-limited devices Equally rare are diaphragmatic hernias that have not been diagnosed antenatally giving problems at resuscitation
If the chest is moving but the heart rate has not responded to resuscitation consider rare possibilities such as fetal blood loss pneumothorax or heart block (mothers with undiagnosed systemic lupus erythematosis delivered for fetal bradycardia) as possibilities With adequate ventilation there is no evidence of oxygen concentrations less than 100 being responsible for prolonged bradycardia or failure to respond although current practice would support increasing the delivered oxygen concen-tration if resuscitation had been commenced using air
Outcome
The prognosis for the full-term baby subjected to sudden acute asphyxia is usually good provided the episode does not last for
paeDiatRiCS anD CHilD HealtH 184 17
long Most babies resuscitated from primary apnoea have no sequelae secondary to the resuscitation Many babies who start to breathe again regularly within 20 min of the circulation being restored recover completely but it is rare for a baby who is still gasping after 30 min to recover
The prognosis for the preterm baby of less than about 34 weeksrsquo gestation subjected to severe acute anoxia is less predict-able This is because of the risk of secondary intraventricular haemorrhage or periventricular intracerebral haemorrhage andor infarction after even a relatively brief asphyxial episode espe-cially in the period immediately around birth
The effects of chronic hypoxia are also difficult to predict but a reasonably clear idea of the extent of the problem should be obtainable within 36ndash48 h of the original chronic asphyxial insult A mild short-lasting state of hyperexcitability usually car-ries a good prognosis even if there is seizure activity but more severe symptoms can be associated with permanent handicap This is seen especially in infants with encephalopathy requiring ventilation
REFERENCEs
1 Biarent D Bingham R Richmond S et al european Resuscitation
Council guidelines for Resuscitation 2005 Section 6 paediatric life
support Resuscitation 2005 67(suppl 1) S97ndashS133
2 international liaison Committee on Resuscitation part 7 neonatal
resuscitation Resuscitation 2005 67 293ndash303
3 Singh J Santosh S Wyllie J mellon a effects of a course in
neonatal resuscitation - evaluation of an educational intervention
on the standard of neonatal resuscitation Resuscitation 2006 68
385ndash389
4 palme-Kilander C methods of resuscitation in low-apgar-score
newborn infants - a national survey Acta Paediatr 1992 81
739ndash744
5 Kroll l twohey l Daubeney p et al Risk factors at delivery and
the need for skilled resuscitation Eur J Obstet Gynecol Reprod Biol
1994 44 175ndash177
6 Wyllie Jp Resuscitation of the newborn The Foundation Years
2007 3(4) 153ndash157
7 Richmond S ed newborn life Support Resuscitation at Birth
london Resuscitation Council 2006
8 Ceriani Cernadas Jm Carroli g pelligrine l et al the effect of timing
of cord clamping on neonatal venous hematocrit values and clinical
outcome at term a randomized controlled trial Pediatrics 2006
117 e779ndashe786
9 mercer JS Vohr BR mcgrath mm padbury JF Wallach m oh W
Delayed cord clamping in very preterm infants reduces the incidence
of intraventricular hemorrhage and late-onset sepsis a randomized
controlled trial Pediatrics 2006 117 1235ndash1242
10 Dahm lS James lS newborn temperature and calculated heat loss
in the delivery room Pediatrics 1972 49 504ndash513
11 Stephenson J Du J tk o the effect of cooling on blood gas
tensions in newborn infants J Pediatr 1970 76 848ndash852
12 gandy gm adamsons Jr K Cunningham n Silverman Wa James lS
thermal environment and acid-base homeostasis in human infants
during the first few hours of life J Clin Invest 1964 43 751ndash758
13 gluck l Kulovich mV eidelman ai et al Biochemical development
of surface activity in mammalian lung pulmonary lecithin synthesis
0 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
in the human fetus and newborn and etiology of the respiratory
distress syndrome Pediatr Res 1972 6 81ndash99
14 Vohra S Roberts RS Zhang B Janes m Schmidt B Heat loss
prevention (Help) in the delivery room a randomised controlled
trial of polyethylene occlusive skin wrapping in very preterm infants
J Pediatr 2004 145 750ndash753
15 owen CJ Wyllie Jp Determination of heart rate in babies at birth
Resuscitation 2004 60 213ndash217
16 orsquoDonnell Cp Kamlin Co Davis pg Carlin JB morley CJ Clinical
assessment of infant colour at delivery Arch Dis Child Fetal
Neonatal Ed 2007 92 F465ndashF467
17 international liaison Committee on Resuscitation part 13 neonatal
Resuscitation guidelines Circulation 2005 112(suppl 24)
iV188ndashiV195
18 leone ta Rich W Finer nn neonatal intubation Success of
pediatric trainees J Pediatr 2005 146 638ndash641
19 orsquoDonnell Cp Kamlin Co Davis pg morley CJ endotracheal
intubation attempts during neonatal resuscitation success
rates duration and adverse effects Pediatrics 2006 117
e16ndash21
20 Repetto Je Donohue pa-CpK Baker SF Kelly l nogee lm use of
capnography in the delivery room for assessment of endotracheal
tube placement J Perinatol 2001 21 284ndash287
21 gandini D Brimacombe JR neonatal resuscitation with laryngeal
mask airway in normal and low birth weight infants Anesth Analg
1999 89 642ndash643
22 esmail n Saleh m ali a laryngeal mask airway versus endotracheal
intubation for apgar score improvement in neonatal resuscitation
Egypt J Anesthiol 2002 18 115ndash121
23 Wiswell te gannon Cm Jacob J et al Delivery room management
of the apparently vigorous meconium-stained neonate results of
the multicenter international collaborative trial Pediatrics 2000
105 1ndash7
24 Vain ne Szyld eg prudent lm Wisewell te aguilar am Vivas ni
oropharyngeal and nasopharyngeal suctioning of meconium-stained
neonates before delivery of their shoulders multicentre randomised
controlled trial Lancet 2004 364 597ndash602
25 Bjorklund lJ ingimarsson J Curstedt t larsson a Robertson B
Werner o lung recruitment at birth does not improve lung function
in immature lambs receiving surfactant Acta Anaes Scand 2001 45
986ndash993
26 Bjorklund lJ ingimarsson J Curstedt t et al manual ventilation
with a few large breaths at birth compromises the therapeutic effect
of subsequent surfactant replacement in immature lambs Pediatr
Res 1997 42 348ndash355
paeDiatRiCS anD CHilD HealtH 184 17
27 taskar V John J evander e Robertson B Jonson B Surfactant
dysfunction makes lungs vulnerable to repetitive collapse and re-
expansion Am J Respir Crit Care Med 1997 155 313ndash320
28 muscedere Jg mullen JB gan K Slutsky aS tidal ventilation at low
airway pressures can augment lung injury Am J Respir Crit Care Med
1994 149 1327ndash1334
29 nilsson R grossman g Robertson B Bronchiolar epithelial lesions
induced in the premature rabbit neonate by short periods of artificial
ventilation Acta Pathol Microbiol Scand 1980 88 359ndash367
30 probyn me Hooper SB Dargaville pa et al positive end expiratory
pressure during resuscitation of premature lambs rapidly improves
blood gases without adversely affecting arterial pressure Pediatr
Res 2004 56 198ndash204
31 Wood Fe morley CJ Dawson Ja et al improved techniques
reduce face mask leak during simulated neonatal resuscitation
study 2 Arch Dis Child Fetal Neonatal Ed in press doi101136
adc2007117788
32 tan a Schulz a orsquoDonnell CpF Davis pg air versus oxygen for
resuscitation of infants at birth Cochrane Database Syst Rev 2004
(3) CD002273
33 Davis pg tan a orsquoDonnell Cp Schulze a Resuscitation of newborn
infants with 100 oxygen or air a systematic review and meta-
analysis Lancet 2004 364 1329ndash1333
34 Dawes g Fetal and neonatal physiology Chicago year Book
publisher 1968 p 141ndash159
35 Ziino aJa Davies mW Davis pg epinephrine for the resuscitation
of apparently stillborn or extremely bradycardic newborn infants
Cochrane Database Syst Rev 2003 (2) CD003849
36 Wyckoff m garcia D margraf l perlman J laptook a Randomized
trial of volume infusion during resuscitation of asphyxiated neonatal
piglets Pediatr Res 2007 61 415ndash420
Practice points
bull Resuscitation at birth is different from that at all other times
of life
bull a standard approach can be applied to most newborn
resuscitation
bull guidelines are based on a rigorous evaluation of evidence
where possible
bull evidence is sparse but evolving
bull most preterm babies require stabilization rather than
resuscitation
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Acidndashbase physiology and blood gas interpretation in the neonateSusern tan
morag Campbell
Abstractacidndashbase balance describes the complex processes that work to main-
tain a stable extracellular pH for optimal cellular function the process
of balancing the production and neutralization of tissue acid provides a
great challenge for newborn infants who have significantly higher rates
of acid production than adults Factors which help maintain a stable
acidndashbase balance include buffers the respiratory system and renal sys-
tem Both intracellular and extracellular buffers resist changes in pH
the most important extracellular buffer system for maintaining stable
pH is the bicarbonate system in response to acidosis or alkalosis the
respiratory system balances the production of acid with the clearance
of Co2 by altering respiratory rate the kidneys provide a delayed but
sustained response to pH imbalance by excreting either acidic or alkaline
urine in response to systemic acidosis and alkalosis respectively in sick
premature infants these systems have a limited capacity completely to
control pH this review discusses the physiology of the three systems
which control acidndashbase balance patterns of clinical abnormalities in
acidndashbase status and their underlying causes are discussed We present
a systematic approach to blood gas analysis and interpretation in new-
born infants
Keywords acidosis alkalosis bicarbonate bloodndashgas analysis
metabolic pH
Introduction
Blood gas analysis is a routine procedure performed on newborn babies receiving respiratory support in the neonatal intensive care The combination of invasive and non-invasive assessment of ventilation and oxygenation enables clinicians appropriately to modify respiratory care according to each individual babyrsquos rapidly changing clinical status
Understanding the fundamentals of acidndashbase balance helps us to use blood gas analysis not only to assess respiratory sta-tus but also to provide information on metabolic status and the adequacy of tissue perfusion
Susern Tan MBBS MRCP is Clinical Fellow at the Neonatal Intensive Care
Unit 6th Floor North Wing St Thomasrsquo Hospital London SE1 7EH UK
Morag Campbell MBChB MRCP is Consultant Neonatologist at the
Neonatal Intensive Care Unit 6th Floor North Wing St Thomasrsquo
Hospital London SE1 7EH UK
paeDiatRiCS anD CHilD HealtH 184 17
What is understood by acid-base balance
Acidndashbase balance refers to the complex physiological processes used by the body to maintain a stable extracellular pH1 A serum pH within the range of 735ndash745 provides the ideal environment for cellular metabolism Maintaining a stable pH is critical as the metabolic activity of proteins is pH dependent and small changes in hydrogen ion (H+) concentration can potentially alter physio-logical function
Acids are substances that yield free H+ in solution while a base accepts H+ and in solution combines with an acid to neu-tralize it In the normal metabolic state H+ are continuously pro-duced and neutralized to maintain a steady pH balance12 The rate of H+ production is two to three times higher in neonates because of their rapid growth rates and increased acid production from protein turnover and bone mineralization The challenge of maintaining a stable pH through processing and neutralizing H+ is therefore greatest in newborn infants
Using exact values of H+ concentration to assess acidndashbase status is cumbersome and it is more commonly expressed as pH defined by the equation
pH = minuslog H+
Maintaining acidndashbase balance
The balance between production and excretion of acids in the body is controlled by buffer systems which have an immediate effect and by the respiratory and the renal systems
Buffer systemsBuffer solutions resist change in pH when acid or alkali is added due to their capacity to absorb or give up H+ The three main buffer systems in the body are the bicarbonate phosphate and protein systems1ndash3 The protein and phosphate buffer systems are intracellular and act as lsquosinksrsquo for extracellular H+ which are exchanged with intracellular potassium (K+) and sodium ions (Na+) In an acute metabolic acidosis hyperkalaemia may develop due to this H+ exchange4
The bicarbonate buffer system is extracellular and consists of a mixture of carbonic acid (H2CO3) and sodium bicarbon-ate (NaHCO3) This buffer system helps maintain a stable pH by soaking up excess H+ with HCO3
minus which in solution forms carbonic acid (H2CO3) Carbonic acid is a weak acid and readily dissociates to give CO2 which is transported in dissolved form to the lungs for excretion
H+ + HCO3minus harr H2CO3 harr H2O + CO2
The bicarbonate system therefore completes the neutraliza-tion of excess H+ and a stable plasma pH is maintained The relationships between pH HCO3
minus and CO2 in this system are described by the HendersonndashHasselbalch equation15
pH = 61 + log HCO3minus003 times CO2
where 61 is the log of the dissociation coefficient of carbonic acid and 003 the solubility of CO2 in plasma Buffers are most potent when there are equal amounts of H+ and HCO3
minus in solution The
2 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
bicarbonate system is not a potent buffer however as HCO3minus
and CO2 are readily altered by the body this system plays a very powerful role in pH homeostasis15
Respiratory regulationThe respiratory system adapts within minutes to hours as part of the acute response to acidosis This system modifies pH by balancing production of H+ with ventilatory clearance of CO2
H+ directly stimulates chemoreceptors in the respiratory cen-tre of the brainstem producing an increase in respiratory rate26 The response to respiratory acidosis is very rapid as CO2 easily diffuses across the bloodndashbrain barrier however in metabolic acidosis compensation is delayed until plasma bicarbonate fully equilibrates with cerebrospinal fluid (CSF) bicarbonate There is an inverse relationship between alveolar ventilation and partial pressure of dissolved carbon dioxide (PaCO2) a reduction in alveolar ventilation raises PaCO2 and decreases pH Changes in pH therefore affect alveolar ventilation and conversely changes in alveolar ventilation cause significant changes in pH
Renal regulationThe kidneys provide a delayed but sustained response to acidndashbase imbalances by excreting either acidic or alkaline urine In full-term and preterm babies the capacity for acid excretion and bicarbonate reabsorption is reduced as glomerular filtration rates are low and tubular function immature7 Renal function matures with gestation postnatal age and glucocorticoid and thyroid hormones78 Due to their limited capacity to preserve HCO3
minus newborn infants have lower serum bicarbonate levels and are predisposed to acidosis7
Bicarbonate is not effectively reabsorbed due to its size and electrical charge Instead intraluminal HCO3
minus combines with secreted H+ in tubular luminal fluid to produce carbonic acid which dissociates to give H2O and CO2 This CO2 diffuses into tubular cells combines with intracellular H2O and forms carbonic acid which liberates HCO3
minus and H+ HCO3minus is then
recovered to the circulation by exchange for chloride ions (Clminus) through the basal cell membrane247
Renal acid secretion occurs at all sites except the loop of Henle Primary active transport accounts for 5 and secondary for the remaining 95 of total H+ excretion Secondary trans-port involves an exchange between luminal Na+ and intracel-lular H+ Both ions bind to a membrane transport protein The Na+ concentration gradient between the tubular lumen and cells enables Na+ drag into the cell which generates energy to fuel active H+ excretion into the tubular lumen1ndash47
Quantifying acidosis
Standard base excess is a calculated value derived from PaCO2 and pH It is expressed as the mmollitre of base above or below normal buffer bases required to correct the pH to 74 at a PaCO2 of 40 mmHg A negative base excess or base deficit indicates an acidosis while a positive base excess indicates a relative alkalosis15
Anion gap is the measured difference between anions and cations in the blood
Anion gap = (Na+ + k+) minus (HCO3+Clminus)
paeDiatRiCS anD CHilD HealtH 184 17
Calculation of the anion gap enables clinicians better to define the underlying cause of a metabolic acidosis9 The common causes of an increased anion gap acidosis in neonates include lactic acidosis due to tissue hypoperfusion and hypoxia it may also be seen with certain inborn errors of metabolism and in uraemia910 The anion gap can help distinguish between the rela-tively benign non-anion gap hyperchloraemic acidosis seen in premature infants and a pathological lactic acidosis due to poor end-organ perfusion1011
Strong ion theory
Stewart described a complex acidndashbase model which proposed that H+ concentration results from the dissociation of water which is influenced by PaCO2 the strong ion difference and plasma weak acids12
Strong ions are ions that dissociate at normal body pH and include Na+ K+ and Clminus Weak acids in plasma which contrib-ute include albumin inorganic phosphate and plasma proteins their concentrations do not change with pH and are therefore a constant The effect of these factors and other unmeasured tissue ions on acidndashbase status can be quantified by the calculation of the strong ion gap (SIG)112 In the neonatal unit it is perhaps more important that we consider how principles of this model may relate to acidndashbase status rather than fully to quantify the SIG Theoretically low albumin and phosphate levels which fre-quently occur in premature infants by reducing the concentra-tion of weak acids can produce a relative alkalosis while high phosphate levels in renal failure may contribute to acidosis
Tissue oxygenation
Oxygenation is closely linked to acidndashbase status as optimal cel-lular function requires oxygen to fuel aerobic metabolism and produce energy In hypoxic conditions anaerobic metabolism predominates which is energy inefficient and results in a lactic acidosis1011
Tissue oxygen availability is related to regional blood flow haemoglobin level and haemoglobin oxygen affinity Arterial blood gases measure the partial pressure of dissolved oxygen (PaO2) which represents a small component of total oxygen con-tent the majority being transported bound to haemoglobin The relationship between percentage haemoglobin saturation (SaO2) and PaO2 is described by the sigmoidal oxyhaemoglobin disso-ciation curve which enables us to relate the two measures to each other235 The affinity of haemoglobin for oxygen is altered by local tissue factors Increases in temperature H+ PaCO2 and 23-diphosphoglycerate (DPG) levels shift the oxyhaemoglobin dissociation curve to the right reducing affinity for oxygen Decreases in temperature H+ PaCO2 and 23-DPG levels shift the curve to the left increasing oxygen affinity1ndash35 In the body haemoglobin oxygen affinity continuously changes increasing in the lungs to enable efficient oxygen uptake and decreasing at tissue level to provide efficient oxygen delivery to metabolically active tissues
Avoiding both hypoxia and hyperoxia is important in the neo-natal unit as deleterious effects of hypoxia are seen in infants with pulmonary hypertension1314 while hyperoxia is associated with an increased incidence of retinopathy of prematurity1516
3 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Clinical acidndashbase imbalances
Clinical acidndashbase imbalances can be respiratory metabolic or a mixture of both These abnormalities may be corrected by the acidndashbase regulatory mechanisms in the body in an attempt to maintain normal pH (Figure 1)
Respiratory acidosisThis occurs when any disorder leads to decreased alveolar ventilation Common causes of respiratory acidosis are listed in Table 1 Reduced respiratory clearance of CO2 means more dissolved CO2 accumulates in the plasma leading to increased production of carbonic acid and H+ Through chemoreceptor stimulation respiratory acidosis rapidly alters ventilation in an attempt to reduce CO226 Chemoreceptor mediated ventila-tory increases may only partly adjust in premature infants with underlying lung disease In babies with a sustained respiratory acidosis eg in chronic lung disease then metabolic compen-sation occurs through increased renal excretion of H+ and reabsorption of HCO3
minus slowly restoring pH to around 80 of normal47
paeDiatRiCS anD CHilD HealtH 184 17
The management of PaCO2 levels in infants receiving mechan-ical ventilation has important clinical implications Premature babies have impaired cerebral autoregulation17 and adverse neurological sequelae are reported in association with high PaCO2 levels18ndash20 Ventilation strategies which advocate lsquoper-missive hypercarbiarsquo have been developed to minimize airways damage from mechanical ventilation21 Published data suggest pulmonary benefits however the safe level of PaCO2 remains to be defined in premature infants2021
Respiratory alkalosisThis occurs when more CO2 is excreted than is produced by the body Pathological conditions leading to respiratory alkalosis are rare Hyperventilation in the neonatal setting is often iatrogenic or may be due to disorders in brainstem control of breathing including hypoxicndashischaemic encephalopathy or primary central nervous system abnormalities (see Table 1)
If respiratory alkalosis is sustained it may be compensated for by reduced reabsorption of filtered bicarbonate Reported adverse associations of low PaCO2 include periventricular leuco-malacia and intraventricular haemorrhage1922
K+
H+
Overventilation
CO2 + H2O harr H2CO3 harr H+ + HCO3ndash
Bicarbonate Buffer
Intracellular Buffer
uarr H+ excretionuarr HCO3
ndash absorption
uarr buffered H+
(NH4+ H2PO4
ndash)uarr ventilation rate
RespiratoryAcidosis
MetabolicAcidosis
darr CO2and uarr pH
RespiratoryAlkalosis
MetabolicAlkalosis
darr H+ anduarr pH
darr ventilation rate
uarrCO2
and darr pH
darr H+ excretiondarr HCO3
ndash absorption
uarrH+ and
darr pH
Brain
Brain
Intracellular Buffer
H+
K+
Sepsis
HypoxiaRDS
Metabolismand growth
Diuretics
Airwayobstruction
Neuromuscularproblems
IEM
Gastric losses
+ +
ndash -
Renal BufferRespiratory Buffer
Figure 1 mechanisms for regulation of extracellular pH iem inborn errors of metabolism RDS respiratory distress syndrome
4 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Common causes of acidndashbase imbalances
pH PCO2 H2CO3 Base excess Common neonatal causes
Respiratory acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
uarr normal normal bull upper airway obstruction choanal atresia
pierre-Robin sequence
bull lung abnormalities respiratory distress
syndrome transient tachypneoa of
newborn pneumonia meconium aspiration
syndrome pulmonary hypoplasia
congenital pulmonary malformations
bull Central hypoventilation hypoxic-ischaemic
encephalopathy intracranial haemorrhage
bull neuromuscular insufficiency congenital
myopathies congenital neuropathies
bull iatrogenic inadequate ventilatory settings
Compensated lower limit
of normal
uarr uarr gt+3
metabolic acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
normal darr ltminus3 increased anion gap
bull lactic acidosis sepsis hypoperfusion
shock necrotizing enterocolitis
bull inorganic acidosis inborn errors of
metabolism renal failure
normal anion gap
bull increased gastrointestinal H2Co3 losses
ileostomy diarrhoea
bull Renal tubular acidoses
Compensated lower limit
of normal
darr darr ltminus3
Respiratory alkalosis Uncompensated gt 745 darr normal normal bull iatrogenic excessive ventilatory settings
bull Compensatory hyperventilation hypoxic-
ischaemic encephalopathy
Compensated higher limit
of normal
darr darr ltminus3
metabolic alkalosis Uncompensated gt 745 normal uarr gt+3 bull gastric losses vomiting non-replacement
of excessive nasogastric aspirates
bull thiazide and loop diuretics
bull Hypokalaemia
Compensated higher limit
of normal
uarr uarr gt+3
Table 1
Metabolic acidosisThis frequently affects infants in the neonatal unit and has many causes1011 (see Table 1) There may be overproduction of tissue acid impaired acid clearance gastrointestinal loss of bicarbonate or an exogenous increased acid load eg chloride total paren-teral nutrition (TPN) or albumin1ndash323
Calculation of the anion gap to distinguish an increased anion gap acidosis from a non-anion gap acidosis is important both for treatment and prognosis1011 Acidosis stimulates respiratory compensation but this is limited in unstable infants Similarly renal compensation with improved HCO3
minus conservation is con-strained by tubular immaturity Treatment of the acidosis should be directed at the underlying cause eg hypoxia hypotension or excess Clminus rather than by administration of base
Metabolic alkalosisThis is unusual in neonates and is most frequently seen in infants with chronic lung disease or heart failure who are receiving diuretics Diuretics cause alkalosis by increasing renal fluid and Na+ losses An active process to reabsorb Na+ occurs in tubule cells which through enhanced H+ secretion and HCO3
minus reab-sorption produce alkalosis27
paeDiatRiCS anD CHilD HealtH 184 17
Metabolic alkalosis may also occur with excessive loss of gas-tric contents eg protracted vomiting or inadequate replacement of nasogastric aspirates (see Table 1)
Interpreting blood gases
Blood gas measurements can provide important diagnostic and prognostic information and a systematic approach to blood gas analysis is described in Table 2 The clinical management of infants with abnormal gases requires a good understanding of acidndashbase physiology and tissue oxygenation and an apprecia-tion of factors which may affect the reliability of samples
Arterial blood sampling is the gold standard however indwelling arterial catheters and arterial stab samples are usually restricted to infants who are critically ill or those who require sig-nificant ongoing intervention Gases are most frequently measured in capillary or venous samples which correlate well with arterial samples for PaCO2 pH and base excess in babies and children receiving intensive care These correlations however are not valid in infants with peripheral vasoconstriction and hypotension2324
Non-invasive monitoring techniques may enable us to reduce the frequency of blood gas sampling Transcutaneous monitoring
5 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
A systematic approach to blood gas analysis
1 Collect the relevant information
bull type of gas ndash capillary or arterial
bull Current respiratory support ndash document level
bull transcutaneous Co2 and Sao2 levels
bull Clarify no significant clinical events before sampling
2 pH accept a range between 730 and 745 in newborn
babies this is lower than in older children is there an
alkalosis (pH gt 745) or an acidosis (lt 730)
3 Co2 aim for a range between 45 and 65 kpa a paCo2 level
more than 65 kpa suggests inadequate alveolar ventilation
while less than 45 kpa suggests hyperventilation Correlate
values with non-invasive measures
4 o2 Can only be assessed from arterial gases aim for pao2
between 60 and 80 kpa Correlate results with pulse
oximetry levels
5 HCo3 and base excess normal HCo3 level is between 20 and
24 mmollitre and bases excess +3 to minus3
6 anion gap look at the anion gap and lactate to help identify
the cause of an acidosis normal lactate levels should be less
than 2 mmollitre
7 Respiratory or metabolic compensation look at the pH and
assess whether it is appropriate for the Co2 level or is there
evidence of compensation
8 interpret use both the clinical history and blood gas
findings to help you identify the primary problem aim your
management at treating the underlying cause
9 Reassess if clinical management changes have been made
repeat the blood gas after an appropriate time interval to
ensure improvement
Table 2
provides a highly accurate and reliable method for measuring PaCO2 through the skin it can however be technically difficult may cause tissue damage and is of limited reliability when peripheral perfusion is reduced25 Continuous end-tidal CO2 measurements correlate well with arterial CO2 values in patients with normal ventilation and perfusion however in babies with lung disease alveolar collapse small tidal volumes and rapid respiratory rates can make these measurements unreliable26 Despite its limitations transcutaneous monitoring provides the best method for CO2 trend monitoring in the neonatal intensive care unit (NICU)25
Oxygen saturation levels can be continuously measured non-invasively using pulse oximetry While oximetry is easy to perform and accurate on occasion SaO2 levels obtained may be unreliable when tissue perfusion is poor or with movement artefact SaO2 monitoring is highly sensitive at detecting hypoxia but is limited in detecting hyperoxia as at levels more than 90 small changes in SaO2 may result in unacceptably large increases in PaO227 It is therefore essential that SaO2 alarm limits are set for all neonates receiving respiratory support to detect hypoxia and prevent hyperoxia1627
Continuous non-invasive monitoring provides invaluable information when managing complex infants in the NICU but it does not replace the need for regular blood gas analysis
paeDiatRiCS anD CHilD HealtH 184 17
ReFeRenCeS
1 Kellum Ja Determinants of blood pH in health and disease
Crit Care 2000 4 6ndash14
2 Quigley R Baum m neonatal acid base balance and disturbances
Semin Perinatol 2004 28 97ndash102
3 Brouillette Rt Waxman DH evaluation of the newbornrsquos blood gas
status Clin Chem 1997 43 215ndash221
4 Chan JC acid-base disorders and the kidney Adv Pediatr 1983 30
401ndash471
5 Siggaard-andersen o the pH-log pCo2 blood acidndashbase nomogram
revised Scand J Lab Invest 1962 14 598ndash604
6 Saetta m mortola Jp interaction of hypoxic and hypercapnic stimuli
on breathing pattern in the newborn rat J Appl Physiol 1987 62
506ndash512
7 Baum m Quigley R postnatal renal development in Seldin DW
giebisch g eds the kidney physiology and pathophysiology new
york lippincott Williams and Wilkins 2000 p 703ndash726
8 ortiz la Quan a Weinberg a et al effect of prenatal
dexamethasone on rat renal development Kidney Int 2001 59
1663ndash1669
9 gabow pa Kaehny WD Fennessey pV goodman Si gross pa
Schrier RW Diagnostic importance of an increased serum anion gap
N Engl J Med 1980 303 854ndash858
10 lorenz Jm Kleinman li markarian K oliver m Fernandez J Serum
anion gap in the differential diagnosis of metabolic acidosis in
critically ill newborns J Pediatr 1999 135 751ndash755
11 Deshpande Sa platt mp association between blood lactate and
acid-base status and mortality in ventilated babies Arch Dis Child
1997 76 F15ndash20
12 Stewart pa modern quantitative acid-base chemistry Can J Physiol
Pharmacol 1983 61 1444ndash1461
13 Dakshinamurti S pathophysiologic mechanisms of persistent
pulmonary hypertension of the newborn Pediatr Pulmonol 2005
39 492ndash503
14 mourani pm ivy DD gao D abman SH pulmonary vascular
effects of inhaled nitric oxide and oxygen tension in
bronchopulmonary dysplasia Am J Respir Crit Care Med 2004
170 1006ndash1013
15 Deulofeut R Critz a adams-Chapman i Sola a avoiding hyperoxia
in infants le 1250 g is associated with improved short- and long-
term outcomes J Perinatol 2006 26 700ndash705
16 Chow lC Wright KW Sola a Can changes in clinical practice
decrease the incidence of severe retinopathy of prematurity in very
low birth weight infants Pediatrics 2003 111 339ndash345
17 Boylan gB young K panerai RB Rennie Jm evans DH Dynamic
cerebral autoregulation in sick newborn infants Pediatr Res 2000
48 12ndash17
18 Kaiser JR gauss CH pont mm Williams DK Hypercapnia during
the first 3 days of life is associated with severe intraventricular
hemorrhage in very low birth weight infants J Perinatol 2006 26
279ndash285
19 Fabres J Carlo Wa phillips V Howard g ambalavanan n Both
extremes of arterial carbon dioxide pressure and the magnitude of
fluctuations in arterial carbon dioxide pressure are associated with
severe intraventricular hemorrhage in preterm infants Pediatrics
2007 119 299ndash305
20 thome uH Carroll W Wu tJ et al outcome of extremely preterm
infants randomized at birth to different paCo2 targets during the
first seven days of life Biol Neonate 2006 90 218ndash225
6 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
21 Carlo Wa Stark aR Wright ll et al minimal ventilation to prevent
bronchopulmonary dysplasia in extremely-low-birth-weight infants
J Pediatr 2002 141 370ndash374
22 okumura a Hayakawa F Kato t et al Hypocarbia in preterm
infants with periventricular leukomalacia the relation between
hypocarbia and mechanical ventilation Pediatrics 2001 107
469ndash475
23 peters o Ryan S matthew l Cheng K lunn J Randomised
controlled trial of acetate in preterm neonates receiving parenteral
nutrition Arch Dis Child 1997 77 F12ndash15
24 yildizda D yapiciolu H yilmaz Hl Sertdemir y Correlation of
simultaneously obtained capillary venous and arterial blood gases
of patients in a paediatric intensive care unit Arch Dis Child 2004
89 176ndash180
25 aliwalas ll noble l nesbitt K et al agreement of carbon
dioxide levels measured by arterial transcutaneous and end tidal
methods in preterm infants 28 weeks gestation J Perinatol 2005
25 26ndash29
26 Hagerty JJ Kleinman me Zurakowski D et al accuracy of a new
low-flow sidestream capnography technology in newborns a pilot
study J Perinatol 2002 22 219ndash225
paeDiatRiCS anD CHilD HealtH 184 17
27 poets CF Wilken m Seidenberg J Southall Dp von der Hardt H
Reliability of a pulse oximeter in the detection of hyperoxemia
J Pediatr 1993 122 87ndash90
Practice points
bull a stable extracellular pH is important for optimal cellular
functioning
bull abnormalities in acidndashbase balance are regulated by buffer
systems and the respiratory and renal tract
bull maintaining a stable pH is challenging for newborn babies
due to their high rates of acid production and immature
regulatory mechanisms
bull arterial or capillary blood gases provide an effective way to
monitor acidndashbase balance in newborns
bull Blood gases should be analysed in a structured manner
assessing pH and then respiratory and metabolic components
bull the treatment of acidndashbase abnormalities should be directed
at the underlying problem not merely at correcting pH
7 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Recognition and management of neonatal seizuresmalcolm levene
AbstractSeizures are the most common major manifestation of central nervous
system dysfunction in the newborn there are many causes but perina-
tal asphyxia and haemorrhagicinfarction lesions account for about 75
there is now considerable evidence that frequent but short seizures in
the neonate affect subsequent neurodevelopmental outcome Studies
using eeg or modified continuous tracing of eeg activity (aeeg or CFm)
have shown that there is often electroconvulsive dissociation this re-
fers to poor correlation between electrical seizures and clinical seizures
Commonly used anticonvulsants appear to increase electroconvulsive
dissociation effective management of neonatal seizures has proved very
disappointing and less than 50 of seizures are abolished by first-line
anticonvulsant medication (phenobarbitone or phenytoin) Drugs such
as midazolam and lidocaine may further reduce seizures but require
more evaluation the challenge is to assess new and more effective anti-
convulsants which are themselves associated with little neurotoxicity
Keywords antiepileptic drugs eeg neonatal seizures neurodegeneration
Convulsions are the most common major neurological sign seen in newborn infants and their incidence estimated from large population studies is 26 per 1000 live births1 Premature infants are over four times more likely to have convulsions than full-term infants12 Neonatal status epilepticus (continuous seizure activity lasting 30 min or more) diagnosed clinically is rare and accounts for only 5 of infants with seizures1 although this is now recognized more frequently as the result of continuous EEG monitoring3
Neonatal convulsions are described as presenting in a num-ber of different ways and various seizure types can be seen in the same baby over a number of hours The frequencies of the various patterns of seizure activity are given in Table 1 In very premature babies and to a lesser extent in term infants minor movement abnormalities may be difficult to identify as subtle seizures These include lip smacking tongue thrusting mouth-ing pedalling type movements of the lower limbs or swimming movements of the arms Apnoea can be a common manifesta-tion of subtle seizures The signs can be protean and vary from baby to baby or even in the same baby Virtually any stereotypic
Malcolm Levene MD FMedSc FRCPCH FRCH is Professor and Head of
Department of Paediatrics and Child Health at University of Leeds Leeds
and Honorary Neonatologist at Leeds General Infirmary Leeds UK
paeDiatRiCS anD CHilD HealtH 184 178
movement may be a manifestation of a seizure disorder in the newborn
Aetiology
The more carefully the fitting baby is investigated the more likely it is that a cause for the seizures will be found A number of recent papers have described the aetiology of neonatal con-vulsions after extensive investigations14 Tekgul et al4 recently studied a consecutive group of full-term infants with evidence of neonatal convulsions (recognized both clinically and on EEG) and reported their outcome Table 2 summarizes these data as well as risk of moderate or severe disability for each causative factor Perinatal asphyxia is the commonest cause for convul-sions in term infants with haemorrhagic or ischaemic lesions also being common
Overall the prognosis for the group of term babies with con-vulsions was good 72 had a favourable outcome Where asphyxia (hypoxicndashischaemic insult) is the cause of neonatal convulsions the outcome is poor in 50 The prognosis for neonatal convulsions when they were due to arterial or cere-brovenous infarction or intracranial haemorrhage was generally good Individually inborn errors are a very rare cause of neo-natal convulsions but in view of the treatable nature of some of these it is essential that these be considered and investigated appropriately5
Patterns of seizure activity in the newborn
Movement pattern Frequency ()
Clonic 50
tonic 20
Subtle 10ndash35 depending on maturity
myoclonic 5
Table 1
Cause incidence and outcome of neonatal convulsions in term infants14
Aetiological factor Incidence () Poor outcome ()
asphyxia 38ndash40 50
Cerebral arteriovenous
infarction
20 0
intracranial haemorrhage 12ndash20 13
Congenital cerebral anomaly 5ndash10 100
Hypoglycaemiahypocalcaemia 3ndash19
infection 3ndash20
inborn error of metabolism 1
unknown cause 10ndash13 0
Refers to moderate and severe neurodevelopmental abnormalitynumbers too small to make meaningful predictions
Table 2
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Controversies in the clinical management of neonatal seizures
In recent years we have learnt much more about the neurobi-ology of seizures and their effect on the developing brain The neonatal brain is in a neurophysiologically hyperexcitable state compared to the more mature brain and therefore is more prone to seizure activity This is due largely to a relative excess of GABA neuroreceptors GABA receptors are usually inhibitory but in the immature brain they have a paradoxically excitatory effect This changes at about term in primates and with progressive develop-ment they adopt a neuroinhibitory role6
The propensity to seizures in the neonatal brain makes resolv-ing the balance of risks between continuing seizure activity on the one hand against potentially adverse effects of therapy on the other a very important equation Added to this is the problem of accurately diagnosing neonatal seizures and whether commonly used anticonvulsants are successful in controlling them
These conundrums can be posed as a series of challenging questions which are discussed below
Do neonatal convulsions cause brain injuryConvulsions are a sign of neurological compromise and may indi-cate significant underlying structural brain damage or biochemi-cal disturbance which may cause further brain damage in its own right There has been considerable debate about the scale of the disability that convulsions cause the immature brain over and above that due to the underlying cause Most of our knowledge comes from studies in rodents and these have provided some tentative answers to this question
Seizures in the mature brain lead to neuronal necrosis but studies in very young rat pups whose brain development is somewhat similar to full-term infants have shown that a series of five brief seizures on five successive days does not cause struc-tural neuronal damage but does produce morphological changes in hippocampal neurones and worryingly deficits in the rat learning and visual spatial memory function in adolescent and adult life7 A single prolonged neonatal convulsion in similarly immature rats does not produce any functional effects8 Others have shown that following priming of the neonatal rat brain by short seizures as described above a further insult comprising induction of status epilepticus in the same rats at an older age causes neuronal necrosis9 This has been referred to as the lsquotwo hit hypothesisrsquo10
A more specific question is does seizure activity in an already significantly compromised brain cause additional neuropathol-ogy Wirrell et al11 studied a series of immature rat pups with the induction of an hypoxicndashischaemic (asphyxial) insult fol-lowed by either chemically-induced fits or a control sham pro-cedure In the more severely asphyxiated animals the degree of brain damage was increased significantly in those that had the additional burden of induced seizures
In summary these studies show that the immature brain is more resistant to short frequent post-seizure damage than the mature brain but despite resulting in no loss of neuronal numbers the function of the brain is permanently affected in later life In the asphyxiated brain seizures appear to have an additional adverse effect on brain damage Furthermore the immature brain that has been lsquoprimedrsquo by early seizures is more
paeDiatRiCS anD CHilD HealtH 184 179
vulnerable to status epilepticus later in life It would appear from these data that frequent seizures in the human infant should be stopped and this begs the question as to whether currently used anticonvulsants effectively control neonatal seizures
Can we rely on clinical versus EEG diagnosis of neonatal convulsionsTraditionally the diagnosis of neonatal convulsions has been made by observation and description of the frequency of abnor-mal movements EEG has been technically difficult in the hostile electrical activity of a neonatal intensive care environment and considerable expertise is required for analysis of the trace It is usually not practical to undertake traditional EEG recordings at the time the baby shows abnormal movements More recently various technological developments have allowed more direct investigation of neuronal electrical activity by either video-EEG or compressed recording of the amplitude integrated EEG (aEEG or CFM)
Rennie et al3 at Kingrsquos College Hospital London have under-taken extensive evaluation of video-EEG and have found that this technique detects many convulsions not recognized by a single channel aEEG or CFM trace Of 19 infants with evidence of convulsions on EEG only four were recognized on CFM but this may have been due to the observersrsquo lack of experi-ence with this technique In other centres that have developed appropriate expertise aEEG or CFM has proved more sensitive to the detection of seizures Video-EEG studies have also shown that many movements interpreted by experienced clinicians to be seizures are not associated with abnormal cortical activity Conversely many electrical seizures are not associated with abnormal movements This is referred to as electroconvulsive dissociation
In summary clinical observation alone to detect the fitting baby is unreliable in that it may either over-detect seizure activ-ity which is not present on EEG or under-detect clinical seizures in infants with EEG-proven convulsions The decision as to which babies to treat with antiepileptic drugs therefore becomes somewhat arbitrary
Do anticonvulsants stop neonatal seizuresAlthough neonatal seizures are common there are few random-ized controlled trials assessing the benefits of antiepileptic drugs (AEDs) in the treatment of this condition Phenobarbitone is the most widely used first-line AED and in an Australasian study 95 of neonatologists and paediatric neurologists used this drug as first-line management12 The most commonly used loading dosage is 20 mgkg but regimens of up to 40 mgkg have been recommended (Table 3)13 Four trials have evaluated the effect of phenobarbitone in abolishing neonatal seizures Two of these studies used EEG to monitor response to the drug1415 and one compared phenobarbitone with phenytoin15 In the latter study seizures were completely controlled in only 43 of babies and in the group where phenytoin was the first drug used com-plete seizure control was achieved in 45 This study switched babies from their first AED to the other if complete control was not obtained on EEG monitoring after exposure to first-line therapy In babies who had been given phenobarbitone as first-line therapy seizure control was only achieved in 57 after phenytoin was added In those given phenytoin first complete
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Dosage regimens for first- second- and third-line anticonvulsants in the neonatal period
Loading dose Second loading dose if first
unsuccessfulMaintenance dose
phenobarbitone 20 mgkg by slow iv injection 10 mgkg iv 25ndash5 mgkg od
phenytoin 20 mgkg iv over 20 min not recommended
midazolam 150ndash200 μgkg iv infusion 1 μgkgmin iv infusion increasing to 5 μgkgmin
until favourable response
lidocaine 2 mgkg iv over 10 min 6 mgkgh for 6 h iv then 4 mgkgh for 12 h then
2 mgkgh for 12 h
lorazepam 005ndash01 mgkg by slow iv injection
Diazepam 03ndash04 mgkg iv over 3ndash5 min
lidocaine should not be used if the infant has previously been treated with phenytoin
Table 3
seizure control was achieved with the adding of phenobarbitone in 62
Boylan et al14 assessed the efficacy of phenobarbitone (20ndash40 mgkg iv over 20 min) in 14 babies monitored by video-EEG in only four was there complete abolition of seizures and in the other 10 electroconvulsive seizure activity increased whereas clinical evidence of seizures reduced This has been termed elec-troclinical dissociation and anticonvulsant drug use in the new-born appears to increase this feature They also showed that the babies least likely to respond to the first-line AED are those with the most abnormal background EEG
Two studies have evaluated the use of phenobarbitone in babies who had sustained significant asphyxial insult at birth Hall et al13 compared high-dose phenobarbitone (mean 39 mgkg) versus standard dose (27 mgkg) and reported fewer convul-sions and a significant reduction of severe disability or death in the high dose group (RR 030 CI 010ndash093) A recent study from India16 of babies with hypoxicndashischaemic encephalopathy ran-domized 25 babies to phenobarbitone (20 mgkg loading dose) and compared them with 20 control babies Only 2 of 25 (4) in the phenobarbitone group developed convulsions compared with 8 of 20 (40) in the control group (p = 001) Because of the specific enrolment criteria (asphyxial insult) neither of these studies is strictly comparable to the studies by Painter et al15 and Boylan et al14 whose intention was to assess the efficacy of first-line anticonvulsant therapy on convulsions of any cause diagnosed either clinically or by EEG
Other anticonvulsants used as second- and third-line drugs have been subject to few studies in the newborn Midazolam is administered as a bolus followed by continuous infusion A recent study17 has shown that in 10 of 13 neonates given intravenous midazolam for status epilepticus control of electri-cal seizures was achieved within the first hour of treatment having been previously shown to be refractory to phenobarbi-tone treatment Some of these babies required a second bolus infusion of midazolam to obtain control of all electrographic seizures
In some parts of Europe lidocaine is used as a third-line anti-convulsant Malingre et al18 evaluated 20 infants refractory to
paeDiatRiCS anD CHilD HealtH 184 180
both phenobarbitone and midazolam and who were then given lidocaine by continuous infusion Lidocaine was effective in abolishing electroconvulsive seizures diagnosed by aEEG in 76 of the treatment courses studied No babies developed cardiac arrhythmias a previously reported complication of lidocaine in older patients As a result of pharmacokinetic studies the dosage regimen has been modified (see Table 3)
In summary phenobarbitone is effective in seizure control in less than 50 of babies and even when combined with phe-nytoin the efficacy of these drugs together remains poor More worrying is the observation that phenobarbitone tends to reduce clinically evident seizures thereby giving the clinician a false sense of security whilst having little or no effect on the num-bers of electroconvulsive disorders This has been summarized appropriately as lsquoafter all these years we still love what doesnrsquot workrsquo19 Both midazolam and lidocaine infusions appear to be effective in abolishing severe seizures in some infants resistant to phenobarbitone Lidocaine should not be given to babies previ-ously exposed to phenytoin for fear of a synergistic adverse effect on cardiac rhythm
Do antiepileptic drugs cause brain damageA riskndashbenefit analysis is needed to evaluate the efficacy of anticonvulsants in stopping neonatal seizures which is poor with standard anticonvulsants as discussed above against the risk of administering the anticonvulsant drugs themselves Phenobarbitone has been reported to have adverse effects on the developing brain including inhibition of brain growth20 neuronal toxicity21 and adverse behavioural and cognitive effects into adult life when administered to young animals22 Phenytoin shows unpredictable plasma levels and potential cardiotoxicity
Recent studies have shown an effect of AED exposure on the developing brain by causing neurodegeneration23 Phenytoin administration to immature rat pups at doses which produce serum levels similar to those achieved in human neonates was associated with widespread neuronal death as a result of apop-tosis (programmed cell death) Phenobarbitone had a similar effect when a dosage regimen similar to 40 mgkg was used and
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
this effect was maximal in the more immature brain Diazepam and clonazepam also resulted in a similar effect Midazolam and lidocaine were not tested in this study The combination of phenobarbitone or phenytoin with diazepam had a particularly profound effect on neurodegeneration
In summary recent data suggest that the commonly used AEDs for neonatal convulsions may in themselves cause neuro-degeneration due to apoptosis with lasting effects on develop-ment Many babies with neonatal convulsions are treated with at least two AEDs and this may produce more severe adverse effects than the seizures themselves
Practical management of neonatal seizures
Assimilation of these data and formulation of a rational policy is difficult when faced with a fitting neonate on an intensive care unit and pressure on the medical staff to lsquodo somethingrsquo but it is important to accept that sometimes doing nothing is preferable to using potentially dangerous drugs in a situation which does not warrant such intervention Many babies who have normal interseizure neurological clinical findings and whose seizures are relatively brief and infrequent probably do not need anticon-vulsant medication A normal or near-normal background EEG trace should reassure the clinician that anticonvulsants can be withheld
Some causes of neonatal convulsions are treatable such as meningitis hypoglycaemia hypocalcaemia and inborn errors of metabolism and each baby should be rapidly and carefully investigated for cause of the convulsions
In some babies clinical assessment of seizures is difficult ie when the baby is very sick small or paralyzed Sometimes it may be difficult to assess the significance of certain movement pat-terns Under these circumstances an EEG may prove to be very helpful In many units EEG is not available out of hours and a simple aEEG or CFM is strongly advised Modern instruments are very simple to apply and prolonged or frequent seizures should be identified with only moderate training The printout can be faxed to a more senior doctor if there is doubt as to what is shown on the trace
The balance of knowledge now is that frequent seizures cause additional damage to the developing brain and that treatment to abolish the seizures is warranted Unfortunately there is little evidence that the majority of seizures can be effectively termi-nated by current standard therapy Furthermore it appears that the more abnormal the background EEG the more difficult it is to control the seizures Nevertheless a written protocol for the management of neonatal convulsions is required on each unit Phenobarbitone and phenytoin remain the mainstay of treat-ment although their effectiveness is disappointing There is little to suggest that midazolam is more effective than lidocaine as third-line therapy but lidocaine is precluded if phenytoin has been previously used
In view of the anxiety as to the neurodegenerative effects on the immature brain of most anticonvulsants used in the neonatal period (particularly when multiple drugs are used) it is prefer-able to use only one drug to maximum dosage before introduc-ing a second In addition the duration of anticonvulsants should be minimized and the drugs stopped at the earliest opportu-nity It is my practice to stop anticonvulsants prior to discharge
paeDiatRiCS anD CHilD HealtH 184 18
from hospital if the baby is neurologically normal on clinical examination
REFEREnCES
1 Ronen gm penney S andrews W the epidemiology of clinical
neonatal seizures in newfoundland a population-based study
J Pediatr 1999 134 71ndash75
2 lanska mJ lanska DJ Baumann RJ et al a population-based study
of neonatal seizures in Fayette County Kentucky Neurology 1995
45 724ndash732
3 Rennie Jm Chorley g Boylan gB et al non-expert use of the
cerebral function monitor for neonatal seizure detection Arch Dis
Child Fetal Neonatal Ed 2004 89 F37ndashF40
4 tekgul H gauvreau K Soul J et al the current etoliologic profile
and neurodevelopmental outcome of seizures in term newborn
infants Pediatrics 2006 117 1270ndash1280
5 Surtees R Wolf n treatable neonatal epilepsy Arch Dis Child 2007
92 659ndash661
6 Ben-ari y Holmes gl effects of seizures on developmental
processes in the immature brain Lancet Neurol 2006 5 1055ndash
1063
7 Holmes gl gairsa Jl Chevassus-au-louis n et al Consequences of
neonatal seizures in the rat morphological and behavioral effects
Ann Neurol 1998 44 845ndash857
8 Stafstrom Ce Chronopoulos a thurber S et al age-dependent
cognitive and behavioural deficits following kainic-acid inducing
seizures Epilepsia 1993 34 420ndash432
9 Schmid R tandon p Stafstrom Ce et al effects of neonatal seizures
on subsequent seizure-induced brain injury Neurology 1999 53
1754ndash1761
10 Hoffmann aF Zhao Q Holmes gl Cognitive impairment following
status epilepticus and recurrent seizures during early development
support for the ldquotwo-hit hypothesisrdquo Epilepsy Behav 2004 5
873ndash877
11 Wirrell eC armstrong ea osman lD et al prolonged seizures
exacerbate perinatal hypoxic-ischemic brain damage Pediatr Res
2001 50 445ndash454
12 Carmo KB Barr p Drug treatment of neonatal seizures by
neonatologists and paediatric neurologists J Paediatr Child Health
2005 41 313ndash316
13 Hall Rt Hall FK Daily DK High-dose phenobarbital therapy in term
newborn infants with severe perinatal asphyxia a randomized
prospective study with three-year follow-up J Pediatr 1998 132
345ndash348
14 Boylan gB Rennie Jm pressler Rm et al phenobarbitone neonatal
seizures and video-eeg Arch Dis Child Fetal Neonatal Ed 2002 86
F165ndash170
15 painter mJ Scher mS Stein aD et al phenobarbital compared with
phenytoin for the treatment of neonatal seizures N Engl J Med
1999 341 485ndash489
16 Singh D Kumar p narang a a randomized controlled trial of
phenobarbital in neonates with hypoxic ischemic encephalopathy
J Matern Fetal Neonatal Med 2005 18 391ndash395
17 Castro Conde JR Borges H Domenech martinez e et al midazolam
in neonatal seizures with no response to phenobarbital Neurology
2005 64 876ndash879
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
18 malingre mm Van Rooij lgm Rademaker Cma et al Development
of an optimal lidocaine infusion strategy for neonatal seizures Eur
J Pediatr 2006 165 598ndash604
19 Sankar R painter mJ neonatal seizures after all these years we still
love what doesnrsquot work Neurology 2005 64 776ndash777
20 Diaz J Schain J Bailey Bg phenobarbital-induced brain growth
retardation in artificially reared rat pups Biol Neonate 1977 32 77ndash82
21 mattson RH phenobarbital toxicity in levy RH Dreifuss Fe
mattson RH et al eds antiepipeptic Drugs 3rd edn new york
Raven 1985 p 341ndash355
22 mikati ma Holmes gl Chronopoulos a et al phenobarbital
modifies seizure-related brain injury in the developing brain Ann
Neurol 1994 36 425ndash453
23 Bittigau p Sifringer m genz K et al antiepileptic drugs and
apoptotic neurodegeneration in the developing brain Proc Natl
Acad Sci U S A 2002 99 15089ndash15094
paeDiatRiCS anD CHilD HealtH 184 182
Practice points
bull the clinician needs to be aware that almost any repetitive
stereotype movement pattern can be a manifestation of
neonatal seizures
bull eeg is important in defining neonatal seizures
bull Frequent short-lived seizures have been shown to cause long-
term neurodevelopmental problems
bull Conventional anticonvulsant medication is ineffective in
abolishing neonatal seizures in greater than 50 of cases
bull there is evidence that exposure of the neonatal brain to
multiple anticonvulsants causes neuronal death
bull Future research is needed to evaluate more effective
anticonvulsants for treating this condition
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
Emotional support for families of sick neonatesMarina nicolaou
cristine Glazebrook
AbstractParents of sick neonates experience high levels of stress anxiety and
depression Most interventions with families of sick infants have focused
on fostering the motherndashinfant relationship through the provision of
information about infant developmental needs or through increased
motherndashinfant contact Many of these studies have reported improved
maternal well-being though there are some concerns about the scope
and practicality of large-scale interventions The few studies to have
prioritized emotional support for parents of sick neonates have pro-
duced encouraging results even interventions requiring relatively few re-
sources such as telephone support parent-to-parent support and group
support have been associated with reduced psychological morbidity for
parents The needs of parents can change throughout their infantrsquos hos-
pitalization and not all want or benefit from the provision of additional
support Thus neonatal intensive care units should aim to provide a
varied flexible and sustainable programme of support options Further
research should focus on the needs of fathers
Keywords mental health neonatal intensive care parents
The admission of an infant to neonatal care is acknowledged to be a source of considerable distress for families This review aims to explore evidence for the psychological impact on families of having an infant in neonatal intensive care and to identify evi-dence for the effectiveness of interventions to promote parental well-being It will conclude with recommendations for strategies to support parents of vulnerable infants and suggestions for fur-ther research
Psychological impact of neonatal care for parents
The majority of research examining the effect on parents of having a sick neonate has focused on families of premature or low birthweight infants Such research has found that parents with a sick neonate exhibit high levels of stress compared to normative samples and to parents of healthy full-term infants1 Singer et al2 examined the stress experienced by mothers of high-risk very low birthweight (VLBW) low-risk VLBW and term
Marina Nicolaou MPhil is a Teaching Assistant at the School of
Community Health Sciences University of Nottingham Nottingham UK
Cristine Glazebrook PhD is a Professor of Health Psychology at the School
of Community Health Sciences University of Nottingham Nottingham UK
PaeDiaTrics anD cHilD HealTH 184 196
infants Several self-report measures were used including the Brief Symptom Inventory the Parenting Stress Index (PSI) the Impact on Family Scale and the Family Inventory of Life Events and Changes (FILE) Mothers of VLBW infants had more psycho-logical distress at 1 month compared to mothers of term infants Mothers of high-risk VLBW infants also reported high psycho-logical distress at 2 years and high levels of parenting stress at 3 years Mothers have also been found to have higher stress levels compared to fathers Shaw et al3 examined the prevalence of acute stress disorder (ASD) in 40 parents whose infants were in the neonatal intensive care unit (NICU) Nearly half of the moth-ers (44) met the criteria for ASD although none of the fathers did Furthermore the severity of the symptoms (measured by the number of concurrent symptoms) was greater for the moth-ers than for the fathers3 The reasons behind this difference have been widely speculated with some believing that it is due to the mothersrsquo greater psychological involvement with the infant as evidenced by their general greater vulnerability to postpartum psychological disorder It could also reflect gender differences in coping style
Having an infant who requires intensive medical care repre-sents a significant emotional burden for families Not only is there extreme anxiety surrounding the infantrsquos health and distress for the childrsquos suffering there is also the unfamiliar and intimidating environment of the NICU to adjust to Hopper in her review of the literature identified sources of stress for parents of sick neo-nates as falling into three areas4 Situational factors included the severity of the infantrsquos illness and how parents adapted to the life crisis of having a sick infant Personal factors involved parental emotions about their roles and the instrumental and informa-tional support which were available to them The third area was classified as environmental sources of stress and included the environment of the NICU and the relationship between parents and members of staff This relationship has been examined by several studies in the nursing literature nurses are seen as ide-ally placed to provide the necessary support and information to parents with sick neonates However whilst some studies have shown that supportive and helpful hospital staff can have a posi-tive effect on parents other studies have highlighted the prob-lems and difficulties which can manifest It has been shown that parents and nurses often have very different ideas about issues eg the necessary skills and competencies needed in an NICU or the characteristics that make a lsquogood motherrsquo
Research has shown that there may be a relationship between high levels of parental stress and an increased likelihood of depression5 Postpartum depression is a psychiatric illness which appears in 10ndash15 of postpartum women Its reported preva-lence rates however have ranged from less than 10 up to 306 depending on the instruments used the population exam-ined and the timing of the research Several factors have been found to be associated with postpartum depression including poor social support and infant-related stressors6 Evidence indi-cates that postnatal depression may be underreported and this is of concern since the mental and psychological health of the mother can affect her relationship with her infant and thus the infantrsquos cognitive and emotional development5 Depressed moth-ers appear to look touch and talk to their infants less frequently and also appear to show fewer positive and more negative faces7 The vocalizations of mothers suffering with depression have also
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
been found to be less effective at promoting cognitive growth and learning in infants8
If researchers are interested in finding ways of providing sup-port for families of sick neonates then they must listen to what such families perceive their needs to be in order to avoid increas-ing anxiety and distress Furthermore the provision of appropri-ate support be it emotional informational or social will enhance parental coping abilities increase self-esteem and reduce anxiety It should be noted though that the research conducted around these issues has often taken lsquosupport needsrsquo as being synony-mous with lsquoinformation needsrsquo Such studies have examined the type the amount and quality of information that parents receive and perceive themselves as needing but have not explored in equal depth the perceived emotional support needs of families who have a sick infant In addition the needs of parents may change throughout their infantrsquos illness Ward examined the per-ceived needs of 52 parents of infants in an NICU9 Parents rated the needs of their hospitalized infant as most important along with the need to be reassured Interestingly they ranked their support needs as least important This research was conducted during the first week of the infantsrsquo hospitalization however which would explain the preoccupation of the parents with the infantrsquos health These results demonstrate that if researchers want to find ways of providing emotional support to parents of sick neonates they must be prepared not only to listen to parents but also to be flexible enough to satisfy the parentsrsquo changing needs and expectations
Interventions aimed at supporting parents
Most interventions that been evaluated in controlled studies have focused on supporting the motherndashinfant relationship and provid-ing information on infant development Many of these interven-tions have included the aim of improving the parental emotional state and thus psychological outcomes such as stress or anxi-ety have been assessed However few studies appear to include fathers This means that strategies implemented to provide emo-tional support to families of sick neonates are often derived from interventions tailored for mothers even though fathers may have different emotional needs
A wide range of interventions with mothers and infants has been evaluated in the NICU Increasing motherndashinfant contact through kangaroo care has been found to reduce maternal anxiety1011 and educational programmes delivered to fami-lies in the NICU have also been associated with reduced emo-tional difficulties in parents12ndash14 Kaaresen and colleagues implemented an intervention which consisted of eight sessions before discharge and four home visits all by trained nurses The sample included 71 premature infants in the intervention group 69 premature infants in the control group and 74 infants in the full-term control group The randomized controlled trial found that the intervention reduced parenting stress in both mothers and fathers of premature infants compared to controls to a level equivalent to parents in the term control group13 At 6 months corrected age mothers of preterm infants who had not received the intervention had total PSI scores which were 17 points higher than the mothers of infants born at term (an effect size of 057) A similar study evaluated the efficacy of an educationalndashbehavioural programmendashCreating Opportunities for
PaeDiaTrics anD cHilD HealTH 184 19
Parent Empowerment (COPE) ndash through a randomized controlled trial with 260 families of premature infants14 COPE was a four-phase educationalndashbehavioural programme which began as early as 2ndash4 d after mothers had given birth and continued until 1 week after discharge from the NICU The programme consisted of audiotaped and written infant behaviour information along with photographs which focused on common behaviours and characteristics of premature infants It also included various par-ent activities in the form of a four-phase workbook which aimed to assist mothers in the implementation of the experimental infor-mation COPE was found significantly to reduce maternal stress in the NICU as well as maternal anxiety and depressive symptoms after hospitalization In contrast a cluster randomized trial of a parenting intervention delivered to mothers of very premature infants from soon after birth showed no benefits for parenting stress1 The authors hypothesized that the intervention had not been of sufficient intensity particularly in the weeks surrounding discharge Neonatal care presents a significant barrier to parent-ing in the early weeks following a very preterm birth and so inter-ventions which focus on the developmental needs of infants and the parentndashchild relationship should particularly aim to support parents as they take on the parenting role There was also concern that the intervention had failed to reach those most at risk
Since large-scale projects can be costly to implement and may often fail to reach the families in most need it may be wiser to focus on intervention programmes which are more practical and easier to implement within a neonatal care setting Research has shown that even interventions which are based on one-off meet-ings with parents of sick neonates can be effective Jotzo and Poets examined the effect of an intervention programme aimed at reducing the severity of traumatic responses as a result of giv-ing birth prematurely15 Their programme consisted of a one-off intervention meeting along with additional psychological help throughout the hospitalization of the infant The meeting cov-ered a variety of issues including a reconstruction of the events shortly before and after the infantrsquos birth relaxation techniques discussion of coping strategies available resources and social support and support during emotional outbursts The measures used included the Impact of Event Scale (IES) and the Peritrau-matic Dissociative Experience Questionnaire At discharge the mothers who received the intervention were found to have a significantly lower traumatic impact as a result of premature birth Furthermore fewer mothers in the intervention group showed symptoms of clinically significant psychological trauma at discharge compared to mothers in the control group (36 vs 76)15 The lsquoParents Circle Programrsquo is another intervention with a similar structure16 This consisted of a 90 min session for parents with the aim of enhancing the developing relationship between parents and infants and to offer parents support A total of 104 parents (59 mothers and 45 fathers) and 44 members of hospital staff were asked to evaluate the programme and their results were analysed using content analysis Families reported gaining perspective on their situation feeling supported becom-ing aware of cues and optimizing interactions and becoming aware of available resources Parents and staff alike felt that participating in the intervention helped parents overcome the difficulties associated with the early time of their infantrsquos hos-pitalization Additional studies have also found positive results with fairly minimal interventions including discussion groups
7 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
in the NICU music during kangaroo care and pairing mothers of sick neonates with trained mothers who had been through similar experiences
Parent support programmes
Parent support programmes (PSPs) which are based in NICUs can provide parents with the opportunity to talk to parents who have been in similar situations and also to discuss their emo-tions with professionals who can help them cope with their situa-tion111718 The parent-to-parent support programme for mothers of preterm infants evaluated by Preyde and Ardal included edu-cational parental support group meetings and individual par-ent-to-parent support (primarily telephone support)19 Measures used included the Parental Stressor Scale NICU the State and the Trait Anxiety Inventories and the Beck Depression Inven-tory After 4 months of participation mothers in the intervention group reported lower levels of stress state anxiety and depres-sion compared to control group mothers The authors speculated however that the participants who were able to meet face to face with other parents were those who benefited the most Hurst conducted a comprehensive survey of an NICU-based PSP This PSP was provided in a variety of formats including a weekly parent support group hospital visitation and 24-h telephone sup-port20 Of the 477 participants 303 families used the PSP dur-ing a 2-year evaluation period with 78 using only one form of support and 18 using two forms Of a sub-sample of 48 parents asked to complete an evaluation of the PSP 92 stated that they would recommend such a programme to other parents Furthermore the majority of parents felt that it made them feel supported and helped them deal with their emotions20 This is an indication that such programmes can be very successful in sup-porting parents throughout their infantrsquos hospitalization It also shows that it can be beneficial to give parents several options and formats when it comes to such support services It is impor-tant to consider though that both the Hurst and the Preyde and Ardal studies found that some participants did not find the sup-port programmes helpful even reporting that they had caused them increased stress and anxiety Therefore it should not be assumed that support programmes will suit every individual and will provide the required support for all parents1920 NICUs need to be flexible enough to provide parents with a range of forms of support to choose from
The increased understanding of the strains that parents of sick neonates have to deal with has also led to efforts to improve customary practices in NICUs Family-centred care focuses on infants and their needs and attempts to redefine the relationship between parents and caregivers These practices strive to provide parents with support during their infantrsquos illness by focusing on freely sharing information and on the collaboration between parents and hospital staff Family-centred care has been found to be associated with several beneficial outcomes including improved parental satisfaction increased parental comfort staff satisfaction and decreased parental stress18 Research is already examining these practices and questioning how these can be improved further Such research reflects the increasing effort focused on lsquohumanizingrsquo the environment in NICUs in order to make parents feel more comfortable about spending time with their infants
PaeDiaTrics anD cHilD HealTH 184 19
Conclusion
Surprisingly few interventions have prioritized the provision of emotional support for parents of sick neonates or accounted for the changing needs and wishes of parents over the course of their infantrsquos care Large-scale supportive education-based inter-ventions have been shown to be effective in reducing parental distress However the feasibility and sustainability of such pro-grammes should also be considered Programmes which require significant additional resources can be expensive and there are also issues of training and quality control Interventions which require significant input from parents may also place additional burdens on families making them potentially less accessible to those most at risk Arguably the aim should be to explore ways of providing acceptable and effective informational support which could be complemented by emotional support from health professionals and from other parents in the unit Increasingly studies are exploring the use of computers and multimedia as an engaging flexible and cost-effective method of targeting indi-vidual needs and providing support and information Such com-puter-based and interactive multimedia interventions have been found to be successful with a range of patient groups and could therefore be examined as a complementary method of providing informational support to families with sick neonates
REfEREnCEs
1 Glazebrook c Marlow n israel c et al randomised trial of a
parenting intervention during neonatal intensive care Arch Dis Child
Fetal Neonatal Ed 2007 92 F438ndash443
2 singer lT salvator a Guo s collin M lilien l Baley J Maternal
psychological distress and parenting stress after the birth of a very
low-birth-weight infant JAMA 1999 281 799ndash805
3 shaw rJ Deblois T ikuta l Ginzburg K Fleisher B Koopman c
acute stress disorder among parents of infants in the neonatal
intensive care nursery Psychosomatics 2006 47 206ndash212
4 Hopper a sources of stress for parents of a sick neonate a
literature review Pediatr Nurs 2000 30 29ndash32
5 Davis l edwards H Mohay H wollin J The impact of very
premature birth on the psychological health of mothers Early Hum
Dev 2003 73 61ndash70
6 Bernazzani O saucier J-F David H Borgeat F Psychosocial
predictors of depressive symptomatology level in postpartum
women J Affect Disord 1997 46 39ndash49
7 Field T infants of depressed mothers Infant Behav Dev 1995 18
1ndash13
8 Kaplan Ps Bachorowski J-a Zarlengo-strouse P child-directed
speech produced by mothers with symptoms of depression fails
to promote associative learning in 4-month-old infants Child Dev
1999 70 560ndash570
9 ward K Perceived needs of parents of critically ill infants in
a neonatal intensive care unit (nicU) Pediatr Nurs 2001 27
281ndash286
10 lai Hl chen cJ Peng Tc et al randomized controlled trial of music
during kangaroo care on maternal state anxiety and preterm infantsrsquo
responses Int J Nurs Stud 2006 43 139ndash146
8 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
11 Tallandini Ma scalembra c Kangaroo mother care and mother-
premature infant dyadic interaction Infant Ment Health J 2006 27
251ndash275
12 Ohgi s Fukuda M akiyama T Gima H effect of an early intervention
programme on low birthweight infants with cerebral injuries
J Paediatr Child Health 2004 40 689ndash695
13 Kaaresen Pi ronning Ja Ulvund se Dahl lB a randomized
controlled trial of the effectiveness of an early-intervention program
in reducing parenting stress after preterm birth Pediatrics 2006
118 e9ndash19
14 Melnyk BM Feinstein nF alpert-Gillis l et al reducing premature
infantsrsquo length of stay and improving parentsrsquo mental health
outcomes with the creating opportunities for parent empowerment
(cOPe) neonatal intensive care unit program a randomized
controlled trial Pediatrics 2006 118 e1414ndash1427
15 Jotzo M Poets cF Helping parents cope with the trauma of
premature birth an evaluation of a trauma-preventive psychological
intervention Pediatrics 2005 115 915ndash919
16 Pearson J andersen K evaluation of a program to promote positive
parenting in the neonatal intensive care unit Neonatal Netw 2001
20 43ndash48
17 roman l lindsay J Boger r et al Parent-to-parent support
initiated in the neonatal intensive care unit Res Nurs Health 1995
18 385ndash394
18 Meyer ec coll cTG lester BM Boukydis cFZ McDonough sM Oh w
Family-based intervention improves maternal psychological well-
being and feeding interaction of preterm infants Pediatrics 1994
93 241ndash246
PaeDiaTrics anD cHilD HealTH 184 19
19 Preyde M ardal F effectiveness of a parent ldquobuddyrdquo program for
mothers of very preterm infants in a neonatal intensive care unit
CMAJ 2003 168 969ndash973
20 Hurst i One size does not fit all Parentsrsquo evaluations of a support
program in a newborn intensive care nursery J Perinat Neonatal
Nurs 2006 20 252ndash261
Practice points
bull Parents of sick neonates experience significant distress and
exhibit higher levels of stress anxiety and depression than
parents of healthy infants
bull educational support emotional support and increased
motherndashinfant contact have been shown to promote maternal
well-being
bull emotional support for fathers has been largely neglected in
the research literature
bull Parents benefit from a choice of supportive facilities which
could include face-to-face sessions with health professionals
telephone support hospital visitation parent-to-parent
support and unit-based group support meetings
bull Parentsrsquo support needs can change during their infantrsquos
hospitalization and not all parents want or benefit from the
provision of additional information and emotional support in
the neonatal unit
9 copy 2008 elsevier ltd all rights reserved
Personal Practice
When should enteral feeds be started in preterm infantsnicholas D embleton
AbstractPaediatricians are regularly faced with the question of when best to start
enteral feeds in preterm infants this is important as longer term out-
come may be compromised by sub-optimal nutrition in early life clinical
factors that may affect the decision to start and the risk and benefits
are discussed
Keywords breast milk feeding nutrition parenteral nutrition
Key points in the history
Alice is lsquonutritionally vulnerablersquo and whilst this may not be immediately apparent it will affect her long term outcome Her energy stores are extremely limited and consist primarily of pro-tein She has less than 5 fat and little energy associated with stored glycogen She is losing about 1 gkgd protein equivalent so she needs at least that and a minimum of 50ndash60 kcalkg of energy just to maintain the status quo let alone grow
Her weight is on the 25th centile Review of any antenatal his-tory may reveal whether fetal growth was normal Fetal growth retardation can occur with a weight greater than 10th centile The presence of antenatal absent or reversed end diastolic flow in the umbilical artery indicates poor gut blood flow This increases the risk of necrotizing enterocolitis (NEC) and might suggest a more cautious approach to starting feeds1
She has no important cardiovascular problems but if she were hypotensive gut blood flow may be low There is no umbilical
Nicholas D Embleton BSC (Hons) MBBS (Hons) MD FRCPCH is Consultant in
Neonatal Medicine at Newcastle Neonatal Service Royal Victoria
Infirmary Newcastle upon Tyne NE1 4LP UK
Should you start feeds at a day of age
alice was born following spontaneous labour at 30 weeksrsquo
gestation she weighed 1300 g and is now 18 h old she was
briefly ventilated and then extubated to continuous positive
airway pressure 12 h ago in 35 oxygen she has had caffeine
citrate but still has intermittent episodes of self-correcting
apnoea she was commenced on iv 10 dextrose but this was
replaced by a parenteral amino acid solution (referred to as
lsquotPnrsquo) along with intralipid at 0900 this morning serum glucose
is 11 mmoll and blood pressure is 42 systolic
PaeDiatrics anD cHilD HealtH 184 20
arterial catheter in situ but there is no good evidence that this should delay the decision to start feeds Her glucose is high but this is quite common in a baby like this Could this be a sign of sepsis Caffeine does not affect the incidence of NEC2 The great-est risk factor for NEC in this case is prematurity
What else might be found on examination
Up until 24 h ago she was swallowing large amounts of amniotic fluid What will have changed since then
General examination should confirm peripheral perfusion lsquogestaltrsquo view (does she look lsquowellrsquo) and cardiovascular status lsquoBowel soundsrsquo are not usually helpful
The most important variable likely to affect gut perfusion is the arterial duct Precordial lsquoheaversquo and a loud murmur are sug-gestive but it is possible to have a significant ductal shunt in a baby with a normal examination Cardiac ultrasound will con-firm this diagnosis It might be better to treat a large shunt first with indometacin and to delay starting feeds for a further 24 h
It is not possible to assess gut perfusion clinically but normal perfusion elsewhere (adequate urine output usually indicates adequate renal perfusion) would be reassuring Most preterm babies have a few abdominal lsquoloopsrsquo visible but a distended abdomen with many palpable loops suggests ileus This might be secondary to sepsis or poor gut blood flow Preterm babies do not pass much meconium in the first 24ndash48 h
Balance of risks between starting and withholding feeds
Alice requires 35ndash4 gkgd of protein and 120 kcalkgd to grow3 This will initially be provided parenterally Delaying feeds increases the risk of gut villous atrophy and prolongs the need for lsquototal parenteral nutrition (TPN)rsquo TPN requires intravenous access and so increases the risk of sepsis and when prolonged use is required combined with the lack of enteral feeding may result in hepatic impairment
Delaying feeds may allow a gut that has been chronically under-perfused to re-establish more normal perfusion although normal gut endocrine function digestive enzyme upregulation and motility require a source of intraluminal nutrients1 A recent study suggested benefit from delaying the introduction of feeds4 but methodologi-cal problems exist5 Although a Cochrane meta-analysis suggested no benefit only two studies were included6 A large UK-based trial is examining the effect of early or late feeding in preterm infants who were born growth retarded following identification of antena-tal absent or reversed end diastolic flow in the umbilical artery7
When starting feeds what volume should be used
There are no good data to guide this decision We start with 24 mlkg (1 mlkgh) and then increase by this amount each day Most babies achieve full enteral feeds (ge150 mlkgd) by a week of age Feeding guidelines improve the outcome8 Measure-ment or assessment of gastric aspirates is not consistently useful in predicting subsequent feeding intolerance or development of NEC Aspirate volumes equivalent to or sometimes greater than the amount given in the preceding 1ndash2 h are usually normal Most aspirates have a greenish colour Thick bloody or intensely bile-stained aspirates require detailed assessment
0 copy 2008 elsevier ltd all rights reserved
Personal Practice
What else affects decisions and outcome
Feeding success is affected by sepsis and NEC Scrupulous atten-tion should be paid to hand washing and intravenous access and blood sampling should be minimized There is no good evidence to support the routine use of pro-kinetic agents or H2 blockers
The most important clinical intervention affecting the occur-rence of NEC is the use of breast milk9 All efforts should be directed at persuading parents of the benefits and supporting the process Some clinicians delay starting feeds for a further 24 h whilst expressed breast milk becomes available Donor breast milk might be equally efficacious10
RefeRenceS
1 Dorling J Kempley s leaf a Feeding growth restricted preterm
infants with abnormal antenatal Doppler results Arch Dis Child Fetal
Neonatal Ed 2005 90 F359ndash363
2 schmidt B roberts rs Davis P et al caffeine therapy for apnea of
prematurity N Engl J Med 2006 354 2112ndash2121
PaeDiatrics anD cHilD HealtH 184 20
3 embleton nD Pang n cooke rJ Postnatal malnutrition and growth
retardation an inevitable consequence of current recommendations
in preterm infants Pediatrics 2001 107 270ndash273
4 Berseth cl Bisquera Ja Paje VU Prolonging small feeding volumes
early in life decreases the incidence of necrotizing enterocolitis in
very low birth weight infants Pediatrics 2003 111 529ndash534
5 Menon G Boyle eM embleton nD et al introduction of enteral
feeds in preterm infants Pediatrics 2004 114 327ndash328
6 Kennedy Ka tyson Je chamnanvanikij s early versus delayed
initiation of progressive enteral feedings for parenterally fed low
birth weight or preterm infants Cochrane Database Syst Rev 2000
cD001970
7 wwwnpeuoxacukadept
8 Patole sK de Klerk n impact of standardised feeding regimens on
incidence of neonatal necrotising enterocolitis a systematic review
and meta-analysis of observational studies Arch Dis Child Fetal
Neonatal Ed 2005 90 F147ndash151
9 lucas a cole tJ Breast milk and neonatal necrotising enterocolitis
Lancet 1990 336 1519ndash1523
10 Boyd ca Quigley Ma Brocklehurst P Donor breast milk versus
infant formula for preterm infants systematic review and meta-
analysis Arch Dis Child Fetal Neonatal Ed 2007 92 F169ndash175
1 copy 2008 elsevier ltd all rights reserved
self-assessment
Case 1A term male infant born to consanguineous parents is assessed at 24 h of age due to poor feeding profuse yellow watery diar-rhoea and irritability He weighed 32 kg at birth and delivery was uneventful There was no polyhydramnios He has been breastfed since birth On examination he is pale with a non-tender but distended abdomen and reduced bowel sounds His weight is 275 kg and he looks dehydrated Examination is otherwise normal
Initial investigations (normal values in parentheses) showed
sodium 149 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 65 mmollitre (25ndash75)
creatinine 147 μmollitre (40ndash110)
chloride 119 mmollitre (95ndash105)
haemoglobin 172 gdl (140ndash200)
White blood cell count 80 times 109litre (100ndash260)
Platelet count 302 times 109litre (150ndash400)
arterial blood gas
ph 720 (730ndash745)
PcO2 23 kPa (46ndash60)
Bicarbonate 68 mmollitre (220ndash260)
Base excess minus186 mmollitre (minus20 to +20)
lactate 59 mmollitre (06ndash24)
An abdominal X-ray shows distended bowel loops with no intramural thickening or pneumoperitoneum (Figure 1)
He was given nil by mouth and received intravenous fluids and antibiotics His dehydration improved but the metabolic acidosis and diarrhoea persisted despite receiving no enteral feeds and the commencement of total parenteral nutrition Blood and stool cultures were negative
1 Which of the following best describes these results Choose ONE answer ONLY from the followingA Hypernatraemia hyperchloraemic metabolic acidosis
with increased anion gapB Hypernatraemia hyperchloraemic metabolic acidosis
with normal anion gap
Manish Sadarangani BM BCh MA MRCPCH is Clinical Research Fellow
at the Department of Paediatrics University of Oxford Centre for
Clinical Vaccinology and Tropical Medicine Churchill Hospital
Oxford OX3 7LJ UK
Shabna Rajapaksa MB BChir MA MRCPCH is Specialist Registrar in
Paediatrics at the Paediatric Intensive Care Unit John Radcliffe
Hospital Oxford OX3 9DU UK
Nicholas Mann MD FRCP FRCPCH DCH is Consultant Paediatrician at the
Department of Paediatrics Royal Berkshire Hospital Reading RG1
5AN UK
self-assessment
C Hypernatraemic dehydration and compensated metabolic acidosis
D Acute renal failureE Renal tubular acidosis
2 What is the likely diagnosis Choose ONE answer ONLY from the followingA Hirschsprung disease ndash long segmentB Cystic fibrosis with meconium ileusC Microvillus inclusion diseaseD Cowrsquos milk protein intoleranceE Lactose intolerance
3 What is the investigation of choice Choose ONE answer ONLY from the followingA Rectal biopsy with staining for acetylcholine receptorsB Immunoreactive trypsinC Gastrointestinal endoscopy and biopsyD Stool microscopy and cultureE Stool reducing substances
Case 2A 4-year-old boy presents with a 3 d history of jaundice and a florid rash He has had orange urine and there is no change in his stool colour His family originate from Kosovo and have lived in the UK for the last 8 years He has never left the UK There is no history of blood transfusion or sex-ual abuse The grandmother was recently diagnosed with hepatitis B
On examination he is well apyrexial and mildly jaundiced with cervical and axillary lymphadenopathy He has an exten-sive papular rash over the face extremities and trunk (Figure 2) There is 3 cm hepatomegaly with no splenomegaly or ascites Examination is otherwise normal
Figure 1 abdominal X-ray of baby
Paediatrics and child health 184 202 copy 2008 elsevier ltd all rights reserved
self-assessment
Initial investigations are as follows
haemoglobin 110 gdl (113ndash135)
White blood cell count 108 times 109litre (50ndash150)
Platelet count 278 times 109litre (150ndash400)
inr 10 (08ndash12)
aPt ratio 10 (08ndash13)
sodium 140 mmollitre (135ndash145)
Potassium 42 mmollitre (35ndash50)
Urea 56 mmollitre (25ndash75)
creatinine 65 μmollitre (45ndash120)
total bilirubin 66 μmollitre (0ndash15)
conjugated bilirubin 23 μmollitre (0ndash10)
alanine aminotransferase (alt) 2033 iUlitre (0ndash35)
alkaline phosphatase 987 iUlitre (71ndash234)
Gamma-glutamyl transferase (GGt) 870 iUlitre (0ndash51)
1 What is the name of this rash Choose ONE answer ONLY from the followingA Erythema multiformeB Erythema migransC GianottiminusCrosti syndromeD EczemaE Dermatitis herpetiformis
2 What is the most likely diagnosis Choose ONE Answer ONLY from the followingA Autoimmune hepatitisB Hepatitis BC Hepatitis DD Wilson diseaseE Alpha-1 antitrypsin deficiency
3 What is the best means of management Choose ONE answer ONLY from the followingA Isolation until the jaundice disappearsB ImmunosuppressionC Copper chelating agents and genetic counsellingD Patient and family education with consideration of
antiviral agentsE Liver transplantation
Case 3A 10-month-old boy presents with 3 weeks of vomiting and constipation ndash he is passing hard stools every 2ndash3 days He has fallen from the 9th to below the 04th centile in the last 6 weeks He passed meconium within the first 24 h of life On examina-tion he looks pale and there are some dysmorphic features ndash a short nose long philtrum and wide mouth He has normal heart sounds with a grade 3 ejection systolic murmur loudest at the upper right sternal edge Examination is otherwise normal
Initial investigations are as follows
haemoglobin 91 gdl (113ndash141)
total white blood cell count 124 times 109litre (60ndash170)
Platelet count 407 times 109litre (150ndash400)
sodium 144 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 78 mmollitre (25ndash75)
creatinine 78 μmollitre (45ndash120)
albumin 52 glitre (35ndash50)
corrected calcium 384 mmollitre (238ndash263)
Phosphate 167 mmollitre (099ndash157)
1 What is the most likely diagnosis Choose ONE answer ONLY from the followingA HyperparathyroidismB Acute leukaemiaC Williams syndromeD Hypervitaminosis DE Familial hypocalciuric hypercalcaemia
2 Which investigation would be most useful in establishing the diagnosis Choose ONE answer ONLY from the followingA Intact parathyroid hormone assayB Blood filmC Fluorescent in-situ hybridization for 7q1123 deletionD 25-hydroxyvitamin D assayE Urine calciumcreatinine ratio
3 Which of the following treatments would not be suitable for this patient Choose ONE answer ONLY from the followingA Low calcium dietB Normal saline infusionC FurosemideD CorticosteroidsE Bisphosphonates
Case 4A 10-week-old girl presents with a 2-day history of poor feed-ing Her mother has been concerned about weakness since birth She only has a flicker of movement in the arms none in the legs and has a weak cry She has been passing urine and opening her bowels normally She was born at full term by normal delivery and did not require any resuscitation at birth Normal fetal movements were felt antenatally and there was no polyhydramnios She is the first child of non- consanguineous parents and there is no significant family his-tory On examination she is alert and fixing and following appropriately She has a weak cry and a weak suck There is reduced central and peripheral tone with marked head lag
Figure 2 rash found on examination
Paediatrics and child health 184 203 copy 2008 elsevier ltd all rights reserved
self-assessment
Muscle power is grade 3 out of 5 in the arms and legs There is no muscle or tongue fasciculation and she has absent reflexes throughout The remainder of the examination is normal
Electromyogram shows irregular polyphasic motor unit potentials with marked instability consistent with a dener-vating and re-innervating process (Figure 3)
1 Which of the following additional investigations may be helpful Choose ONE answer ONLY from the followingA Nerve conduction studiesB Creatine kinase assayC Muscle biopsyD SMN1 gene analysisE All of the above
2 What is the most likely cause of this childrsquos symptoms Choose ONE answer ONLY from the followingA Congenital myotonic dystrophyB Duchenne muscular dystrophyC PraderminusWilli syndromeD Spinal muscular atrophyE Mitochondrial myopathy
3 What is the mode of inheritance of this disease Choose ONE answer ONLY from the followingA X-linked recessiveB Autosomal recessiveC Autosomal dominantD MitochondrialE Sporadic
Case 5A 13-year-old girl presents with a 3-week history of fever up to 40degC night sweats and headache She has a reduced appetite with some weight loss She has no other specific symptoms She was on holiday in China 7 months ago On examination she looks well and has a temperature of 387degC There is no lymphadenopathy and no rashes Examination is entirely normal
Results of investigations are as follows
haemoglobin 126 gdl (120ndash160)
total white blood cell count 132 times 109litre (43ndash108)
neutrophil count 115 times 109litre (25ndash75)
Platelet count 244 times 109litre (150ndash400)
Blood film neutrophilia with left shift
erythrocyte sedimentation rate 63 mmh (1ndash20)
c-reactive protein 219 mglitre (0ndash5)
Blood culture Streptococcus intermedius
from anaerobic bottle only
csf culture negative
Magnetic resonance imaging (MRI) of the brain shows acute frontal sinusitis with a large intracranial frontal extra-dural empyema (Figure 4)
1 Which of the following would be appropriate management Choose ONE answer ONLY from the followingA A 12-week course of intravenous antibioticsB Drainage of the frontal sinus followed by 2 weeks of
intravenous antibioticsC Drainage of the empyema followed by 2 weeks of
intravenous antibioticsD Drainage of the empyema and the frontal sinus
followed by 2 weeks of oral antibiotics
1151
1152
1153
1154
1155
1156
1157
1158
1159
1200
50ms 1mV
Figure 3 electromyogram recording from the patient Figure 4 Parasagittal section from mri scan of patient
Paediatrics and child health 184 204 copy 2008 elsevier ltd all rights reserved
self-assessment
E Drainage of the empyema and the frontal sinus followed by 8 weeks of intravenous antibiotics
2 Streptococcus intermedius is a potential pathogen in which of the following infections Choose ONE answer ONLY from the followingA Liver abscessB Urinary tract infectionC MeningitisD Thoracic empyemaE Pneumonia
3 Which of the following statements regarding lsquopyrexia of unknown originrsquo in children is false Choose ONE answer ONLY from the followingA Malignancy is the underlying pathology in 5ndash15 of
casesB An aetiology will be found in over 90 of casesC The most common cause is infectionD A rheumatological cause is found in 10ndash20 of casesE Familial Mediterranean fever can occur in children of
non-Mediterranean ethnicity
Answers
Case 11 AThe anion gap is a useful tool to differentiate the causes of a metabolic acidosis It is calculated by the equation
Anion gap = [Na K ] [Cl HCO ]3+ + minus minus+ minus +
It represents the effect of unmeasured anions on the plasma pH and is normally 10ndash18 mmollitre
2 CMicrovillus inclusion disease is a severe autosomal recessive enteropathy that is typically apparent within hours or days after birth It is the second most common cause of protracted diarrhoea in the newborn after infectious causes It is characterized by severe yellow watery diarrhoea and malabsorption due to hypoplasia andor atrophy of the villi of the small intestine secondary to an inherited defect in the brush border membrane This results in severe dehydration malnutrition and metabolic acidosis due to bicarbonate loss from the gut
3 CDiagnosis of microvillus inclusion disease is made on small bowel biopsy Electron microscopy findings are of intracellular brush border inclusions and densely packed apical cytoplasmic vesicular bodies indicating microvillous atrophy There is no cure Treatment is supportive with total parenteral nutrition and consideration of small bowel transplantation
Further reAding
Goulet O ruemmele f causes and management of intestinal failure
in children Gastroenterology 2006 130(suppl 1) s16ndash28
rhoads Jm Vogler rc lacey sr et al microvillus inclusion disease
In vitro jejunal electrolyte transport Gastroenterology 1991
100 811ndash817
Case 21 CGianottindashCrosti syndrome is a distinct self-limiting rash commonly associated with viral infections in children between 2 and 6 years of age It presents as multiple pink to redminusbrown papules or papulovesicles which may be pruritic and can become confluent Gianotti and Crosti initially described the exanthema as associated with hepatitis B virus and they termed it papular acrodermatitis of childhood It can occur in several viral diseases eg hepatitis A B and C coxsackie viruses and cytomegalovirus
2 BHepatitis is a syndrome characterized by inflammation or injury of liver cells which may develop into cell necrosis and subsequently fibrosis andor cirrhosis Biochemically there are raised liver enzymes The degree of transaminase elevation does not correlate with the severity of the disease process Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of viral hepatitis
3 DHepatitis B infection is transmitted via blood sexually or vertically Infection may be acute or chronic Diagnostic markers are the presence of surface antigen (HBsAg) and HBV DNA The presence of e antigen (HBeAg) indicates high infectivity Infected newborns have a 95 risk of becoming carriers this risk decreases with infection acquired later in childhood Approximately 15ndash25 of HBV carriers will die from cirrhosis or hepatocellular carcinoma Extrahepatic findings are more common in older children and include membranous glomerulonephritis and GianottiminusCrosti syndrome Fulminant hepatic failure occurs in severe cases resulting in persistent jaundice encephalopathy and coagulopathy Management includes counselling family members monitoring for ongoing liver disease and consideration of antiviral therapy
Further reAding
Brandt O abeck d Gianotti r Burgdorf W Gianotti crosti
syndrome J Am Acad Dermatol 2006 54 136ndash145
slowik mK Jhaveri r hepatitis B and c viruses in infants and
young children Semin Pediatr Infect Dis 2005 16 296ndash305
Case 31 CHypercalcaemia is uncommon in infancy The most common symptoms in this age group are irritability vomiting and constipation It may be a manifestation of Williams syndrome vitamin D or calcium excess as well as disorders associated with reduced bone formation such as hypophosphatasia or increased bone resorption such as malignancy Occasionally
Paediatrics and child health 184 205 copy 2008 elsevier ltd all rights reserved
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-
SympoSium neonatology
such as EPICure and CESDI 2728 have shown that many of these babies are cold by the time of admission to the neo-natal unit In a study from the USA of 5277 babies with a birthweight below 1500 g in the Neonatal Research Network only 108 had an admission temperature of 37 degC or above In nearly half the babies the first recorded temperature was below 36 degC Admission temperature was inversely related to mortality (28 increase per 1 degC) and late-onset sepsis There was an association of low temperature with the need for intubation at delivery suggesting that radiant heat alone had not been sufficient to offset the heat losses during prolonged resuscitation11
A baby exchanges heat with their environment by conduc-tion radiation convection and evaporation The preterm baby is at high risk of net heat loss because of a high surface area to volume ratio and increased transepidermal water loss resulting in heat lost by evaporation The normal surge in metabolic rate which occurs after birth is much reduced limiting the production of heat from the mobilization of brown fat The development in the control of skin blood flow is also delayed in the imma-ture baby reducing their ability to maintain heat by peripheral vasoconstriction12
Evaporation is the major mechanism of heat loss during resus-citation The baby will lose 560 cal for every millilitre of water evaporated from the skin (the heat of evaporation) Vohra et al have shown that using polyethylene occlusive skin wrapping around the body up to the neck during resuscitation of preterm babies under 28 weeksrsquo gestation significantly improves the central temperature on admission to the neonatal unit13 This is due to a reduction in evaporative heat losses In this random-ized study comparing rectal temperature on admission of babies wrapped at birth with those managed without wrapping body size was an important determinant of heat loss the mean rectal temperature increasing by 021degC with each 100 g increase in birthweight
The use of plastic bags leaving just the head exposed has also been found to be effective in reducing transepidermal water and heat losses during resuscitation14 It is important not to expose the skin once the baby is in the plastic bag ndash clini-cal inspection and auscultation can be done through the bag and if vascular access is needed a small hole can be cut in the plastic
Whether a plastic bag or occlusive dressing is used it is important to remember that there is still significant heat losses from the head which should be covered with a hat during resus-citation and stabilization15
Concern has been expressed about hyperthermia in some babies possibly secondary to the use of occlusive dressings or plastic bags16 Two babies in the study by Vohra et al13 had a rectal temperature above 375 degC In a small study from Edin-burgh 11 of 27 babies under 28 weeksrsquo gestation managed in plastic bags were found to have an admission temperature above 375 degC Of these eight were above this temperature from birth possibly associated with a maternal pyrexia while in the other three the temperature increased (by no greater than 06 degC) after being placed in the bag17
Preventing evaporative heat loss using occlusive dressings or plastic bags has been shown to be effective in preventing hypothermia after delivery at least in babies under 29 weeksrsquo
paeDiatRiCS anD CHilD HealtH 184 15
gestation A Cochrane review concludes that in this group con-sideration should be given to their use in the delivery suite18
No study has yet been powered to show that these treatments reduce neonatal mortality and long term outcome has not been evaluated Further large high quality randomized controlled tri-als are still needed Not least we need to confirm that the mem-brane wrapped around the infantrsquos trunk does not damage the immature skin
Transport
The transport of the newborn baby particularly the preterm infant presents many challenges Transport is not only between units but also within a hospital eg from the delivery suite to the neonatal unit or to and from the radiology department or the operating room
The most effective mode of transport within a hospital building will depend on the local configuration Newly designed neonatal units should be closely linked to the delivery suite to prevent the need for transport over long distances along draughty corri-dors A randomized controlled study comparing transfer from the delivery suite to the neonatal unit of babies under 28 weeksrsquo ges-tation using a radiant warmer or a transport incubator showed no difference in admission temperature in the two groups19 All babies in both groups had been managed with occlusive wrap-ping in the delivery room
Transfer between units is most commonly by road in an ambulance Although incubators are heated there is likely to be high radiative heat losses especially in cold weather This can be reduced by covering the incubator and by using blankets around the baby Evaporative heat losses can be reduced by using a plas-tic bag There will be high evaporative heat losses from the respi-ratory tract if ventilator gases are not heated and humidified Heated gel mattresses which warm patients through release of latent heat of crystallization can be used during transport The baby gains heat by conduction Safe use of this device is critically dependent on gel temperature at the point of activation20
Thermal care within the neonatal unit
The full-term newborn infant will maintain a normal temperature if nursed fully dressed in a cot in a warm room Recommenda-tions for optimum environmental conditions for nursing healthy infants in the newborn period have been published21
Skin-to-skin contact is an effective way of maintaining body temperature even in the very preterm infants2223
The preterm baby even if well may be unable to maintain an adequate temperature without some additional source of heat There are a variety of ways of providing this including incuba-tors radiant heaters and heated mattresses The heated gel- or water-filled mattress is very effective in helping maintain the temperature of the well preterm baby while allowing easy access for parents and staff
Clothes act as a significant thermal barrier to heat loss New-born infants needing intensive or high dependency care are often nursed naked to allow close observation and easy access for examination and treatment This significantly affects tempera-ture control as the resistance to heat loss of a naked baby is three times less than that of a clothed wrapped infant2425
6 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Control of the thermal environment is important for all babies but it is the unwell immature babies who present the greatest challenge They are usually nursed either in an incubator or on an open platform under a radiant heater The early clinical trials of Silverman and others showed that the use of incuba-tors to keep babies warm improved outcome There have never been any controlled studies that show that radiant heaters are as effective clinically Babies nursed with similar skin temperatures have a higher basal metabolic rate when managed under radi-ant heaters compared with incubators26 However no study has shown any significant difference in outcome for babies nursed using either of these devices although Meyer et al27 reported a non-significant trend to better outcome in babies nursed under a radiant heater
Transepidermal water loss
Silverman in the 1950s showed that babies are better able to maintain their body temperature in a humid environment com-pared with a dry environment28
In the 1970s it became possible to measure the evaporation rate of water from the skin surface29 Transepidermal water losses (TEWL) are high in the immature baby At 26 weeksrsquo gestation on day 1 of life the baby can lose over 50 kcalkg by evapora-tion compared with less than 5 kcalkg in the term infant30 Data from Hammerlund et al30 suggest that the skin matures rapidly after birth and adult losses are reached around 10 d of age in all babies After this time the major source of heat loss in all babies is from radiation More recently others have shown that in the very immature baby the maturation of the skin may take longer and 30 weeksrsquo corrected age is a better estimate of the time taken to reach adult TEWL31 In practical terms the amount of trans-epidermal fluid losses after about 14 d are unlikely to remain a major problem
Evaporative water loss from the skin depends on the ambi-ent water vapour pressure irrespective of how the baby is being nursed The high rate of evaporation during care under a radiant heater is due to the low ambient water vapour pressure and not any direct effect of non-ionizing radiation on the skin32
TEWL results in loss of both heat and fluid Under a radi-ant heater the temperature of the baby is maintained because of radiant heat gain but the large fluid losses can be a seri-ous problem Various interventions can help reduce evaporative fluid losses mainly from the skin but also from the respiratory tract
IncubatorsWithin an incubator it is relatively easy to raise the ambient water vapour pressure by introducing humidity within the can-opy The use of a relative humidity of 80 for the first 7ndash10 d of life significantly reduces TEWL in even the most immature infant30 Modern designs use a sealed water system to produce the humidity minimizing the concerns about possible increased infection risk in humidified incubators
Opening the incubator portholes results in a rapid fall in humidity although the air temperature within the canopy is maintained The handling of babies within incubators has been shown to be associated with increased thermal stress33 and it is likely that this is due to the fall in environmental humidity
paeDiatRiCS anD CHilD HealtH 184 15
resulting in increased evaporative heat losses Increasing the air temperature will compensate for the heat loss but incubators are relatively slow to respond to such changes
High humidity within the incubator can cause lsquorain outrsquo on the inside of the canopy This is caused by water condensing on the cold walls and can be minimized by ensuring an adequate environmental temperature within the nursery (around 28 degC)
Radiant heatersTEWL is the major problem in babies nursed under radiant heaters A shield or plastic blanket can be used to cover the baby and create a humidified microenvironment Warm humid-ified air can be passed under the shield or blanket but care must be taken to control the temperature and to make sure it does not affect the skin servo probe attached to the baby If the cover is removed the humidity falls rapidly and the baby starts to lose large amounts of fluid The radiant heater will compen-sate for any fall in the babyrsquos temperature but fluid losses are a concern
Maintenance of skin integrityDamage to the fragile skin of the preterm baby occurs easily and results in a significant increases both in TEWL and the risk of infection Maintaining skin integrity is very important and any adhesives on the skin should be kept to a minimum
Skin coveringsTransparent adhesive dressings on the skin reduce fluid loss but cause significant damage making them impractical
Use of semipermeable non-adhesive dressings lowers TEWL and reduces the bacteria number in the covered skin34 In a ran-domized controlled trial in infants less than 1000 g the skin cov-ered with a semipermeable membrane was in better condition but there were no significant differences in fluid requirements or electrolyte status35
Emollients are used to cover the skin and prevent fluid loss They have been shown to be safe and do not cause burns when exposed to radiant heat or phototherapy Their use reduces excessive drying skin cracking and fissuring However the effect of these products wears off after about 3 h necessitating repeated application36 Treated infants had better skin scores and there were no differences in bacterial skin counts fungal counts or colonization patterns or fluid requirements and electrolyte status37
Ventilator humidityThere can be high fluid and heat losses from the respiratory tract of the ventilated baby It is important to use adequate humidifi-cation in all ventilator circuits
PhototherapyThe effect of phototherapy on TEWL is variable No change was found in a group of thermally stable infants38 yet others have reported an increase in TEWL despite skin temperature and rela-tive humidity remaining unchanged39 Rather than increase fluid intake just because phototherapy has been started fluid balance should be individually monitored and adjusted if necessary
Modern phototherapy units produce little heat but there is still some increase in the temperature of the top of the incubator
7 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
canopy This will reduce radiative heat losses and the incubator air temperature may have to be reduced to prevent a rise in the babyrsquos temperature
Transepidermal water loss and skin maturationTransepidermal movement of water is essential for the acceler-ated maturation of the skin of the immature baby40 It also helps in maintaining the epidermal barrier function41
Use of high ambient humidity in nursing preterm babies under 28 weeksrsquo gestation has been shown to reduce the rate of promo-tion of skin barrier development42
More work in the immature baby is needed to determine the optimum level and duration of environmental humidity as well as the associated benefits and risks of use and the effects of humidification on clinically important outcomes43
Temperature monitoring and its interpretation
The concept of the neutral thermal environment in which a baby uses a minimum of energy to maintain thermal stability has proven useful in determining the optimum environmental temperature for nursing the newborn baby4445 The published data are now old and do not include any allowance for added humidity This makes them less useful in the care of the very immature baby
The way a baby interacts with their environment is always changing and whatever settings are first used it is necessary to monitor continuously the thermal balance Continuous mea-surement of oxygen consumption to allow calculation of energy expenditure is not practical and in normal day-to-day care tem-perature monitoring is the only means of assessing the thermal stability of the baby
There is no single deep body temperature as this will vary depending on the metabolic rate of a particular tissue The brain has the highest temperature of any organ within the body It is however possible to find a central temperature that is representa-tive of deep body temperature Trends in this temperature reflect changes in the deep body temperatures of the body at least with sufficient accuracy for day-to-day clinical care
Traditionally rectal temperature has been used as the mea-sure of deep body temperature This is still used commonly in many countries but less so in UK There is a significant risk of damage to the mucosa of the rectum Also rectal temperature is unreliable being affected by the depth of insertion of the ther-mometer whether the baby has just passed a stool and by the temperature of the blood returning from the lower limbs It is difficult to retain the probes in the same position making this an unreliable site for continuous temperature monitoring
The temperature in the oesophagus at the level of the heart gives a measure of the temperature of the blood in the great veins returning from the body This is possibly the best overall representation of the lsquodeep body temperaturersquo Measurement of oesophageal temperature is however very invasive and not suit-able for clinical monitoring
The temperature of the skin over the liver or in the axilla reflects central temperature Actual values will be lower than the deep body temperatures but in the immature baby these sites can be used to show the trend in central temperature A more accurate measurement can be obtained by placing the
paeDiatRiCS anD CHilD HealtH 184 15
probe between the scapulae and a non-conducting mattress No tape is needed on the skin as the baby lies on the probe holding it in place If the probe is over an area of skin from which no heat can be lost by conduction convection radia-tion or evaporation then with heat flow from the centre of the body to the skin down a temperature gradient this area of skin will warm up to the same temperature as the bodyrsquos core This so-called zero heat flux temperature has been shown to be very close to the central temperature as measured by an oesophageal probe46
The measurement of a single temperature tells us how well the baby is maintaining that temperature but nothing about how much energy is being used to achieve thermal balance The continuous measurement and display of a central (abdominal axilla or zero heat flux) and a peripheral (sole of the foot) tem-perature detects cold stress with the peripheral temperature fall-ing before the central measurement changes
The preterm baby who appears to be comfortable in their environment will have a central temperature measured from a skin probe of 368ndash373 degC and a centralndashperipheral temperature difference of 05ndash1 degC An increasing centralndashperipheral tempera-ture difference particularly above 2 degC is usually due to cold stress and occurs before any fall in central temperature12
Hypovolaemic babies will vasoconstrict their peripheral circu-lation in an attempt to maintain blood pressure This results in an increase in the centralndashperipheral temperature difference but in such cases there are usually other signs of hypovolaemia such as rising heart rate and falling blood pressure12
A high central temperature particularly if unstable along with a wide centralndashperipheral gap is seen in septic babies47
Conclusion
Although we have known for a very long time the importance of maintaining the temperature of the newborn we are still faced with new challenges in the care of the sick immature baby Tem-perature control during their period of adaptation to extrauterine life is often poor and allowing these vulnerable babies to cool is associated with adverse outcome Simple measures can prevent hypothermia following delivery If cold at birth is associated with poor outcome there is no reason to believe that preventing ther-mal stress is any less important once the baby is in the neonatal unit It is important that the risks and benefits associated with various methods of controlling the infantrsquos temperature are fully understood
RefeRenCeS
1 Cone te perspectives in neonatology in Sith gF Vidyasagar D eds
Historical Review and Recent advances in neonatal and perinatal
medicine mead Johnson nutritional Division 1983 p 9ndash33
2 Silverman Wa Fertig JW Berger ap the influence of the thermal
environment upon survival of newly born preterm infants Pediatrics
1958 22 876ndash885
3 Silverman Wa agate FJ Fertig JW a sequential trial of the
nonthermal effect of atmospheric humidity on survival of human
infants of low birth weight Pediatrics 1963 31 710ndash724
8 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
4 Costeloe K Hennessy e gibson at marlow n Wilkinson aR for the
epiCure Study group the epiCure study outcomes to discharge
from hospital for infants born at the threshold of viability Pediatrics
2000 196 659ndash671
5 CeSDi project 2728 available from wwwcemachorguk
publicationsp2728mainreportpdf
6 parry g tucker J tarnow-mordi W for the uK neonatal Staffing
Study Collaborative group CRiB ii an update of the clinical risk
index for babies score Lancet 2003 361 1789ndash1791
7 Richardson DK Corcoran JD escobar gJ et al Snap-ii and Snappe-ii
simplified newborn illness severity and mortality risk scores
J Pediatr 2001 138 92ndash100
8 Wyatt JS gluckman pD liu py et al CoolCap Study group
Determinants of outcomes after head cooling for neonatal
encephalopathy Pediatrics 2007 119 912ndash921
9 yager Jy armstrong ea Jaharus C Saucier Dm Wirrell eC preventing
hyperthermia decreases brain damage following neonatal-ischemic
seizures Brain Res 2004 1011 48ndash57
10 Harned Jr HS Herrington Rt Ferreiro Ji the effects of immersion
and temperature on respiration in newborn lambs Pediatrics 1970
45 598ndash605
11 laptook aR Salhab W Bhaskar B neonatal Research network
admission temperature of low birth weight infants predictors and
associated morbidities Pediatrics 2007 119 e643ndash649
12 lyon aJ pikaar me Badger p mcintosh n temperature control in
infants less than 1000g birthweight in the first 5 days of life Arch
Dis Child 1997 76 F47ndash50
13 Vohra S Roberts RS Zhang B Janes m Schmidt B Heat loss
prevention (Help) in the delivery room a randomized controlled
trial of polyethylene occlusive skin wrapping in very preterm infants
J Pediatr 2004 145 750ndash753
14 lyon aJ Stenson B Cold comfort for babies Arch Dis Child Fetal
Neonatal Ed 2004 89 F93ndash94
15 Stothers JK Head insulation and heat loss in the newborn Arch Dis
Child 1981 56 530ndash534
16 newton t Watkinson m preventing hypothermia at birth in
preterm babies at a cost of overheating some Arch Dis Child Fetal
Neonatal Ed 2003 88 F256
17 Smith Cl Quine D mcCrosson F armstrong l lyon a Stenson B
Changes in body temperature after birth in preterm infants
stabilised in polythene bags Arch Dis Child Fetal Neonatal Ed 2005
90 F444
18 mcCall em alderdice Fa Halliday Hl Jenkins Jg Vohra S
interventions to prevent hypothermia at birth in preterm andor low
birthweight babies Cochrane Database of Systematic Reviews 2005
issue 1 art noCD004210 doi10100214651858CD004210pub2
19 meyer mp Bold gt admission temperatures following radiant
warmer or incubator transport for preterm infants lt 28 weeks
a randomised study Arch Dis Child Fetal Neonatal Ed 2007 92
F295ndash297
20 Carmichael a mcCullough S Kempley St Critical dependence of
acetate thermal mattress on gel activation temperature Arch Dis
Child Fetal Neonatal Ed 2007 92 F44ndash45
21 Hey en the care of babies in incubators in gairdner D Hull D
eds Recent advances in paediatrics 4th edn london J amp a
Churchill 1971 p 171ndash216
22 Whitelaw a Heisterkamp g Sleath K acolet D Richard m Skin-to-
skin contact for very low birthweight infants and their mothers Arch
Dis Child 1988 63 1377ndash1381
paeDiatRiCS anD CHilD HealtH 184 15
23 Bauer K pyper a Sperling p uhrig C Versmold H effects of
gestational and postnatal age on body temperature oxygen
consumption and activity during early skin-to-skin contact between
preterm infants of 25ndash30-week gestation and their mothers Pediatr
Res 1998 44 247ndash251
24 Hey en Katz g orsquoConnell B the total thermal insulation of the
newborn baby J Physiol 1970 207 683ndash689
25 Hey en temperature regulation in sick infants in tinker J Rapin m
eds Care of the Critically ill patient Berlin Springer 1983 p
1013ndash1029
26 leBlanc mH Relative efficacy of an incubator and an open warmer
in producing thermoneutrality for the small premature infant
Pediatrics 1982 69 439ndash445
27 meyer mp payton mJ Salmon a Hutchinson C deKlerk a
a clinical comparison of radiant warmer and incubator care for
preterm infants from birth to 1800grms Pediatrics 2001 108
395ndash401
28 Silverman Wa Blanc Wa effect of humidity on survival of newly
born premature infants Pediatrics 1957 20 477ndash487
29 Hammarlund K Sedin g transepidermal water loss in newborn
infants iii relation to gestational age Acta Paediatr Scand 1979
68 795ndash801
30 Hammerlund K Stroumlmberg B Sedin g Heat loss from the skin of
preterm and fullterm newborn infants during the first weeks after
birth Biol Neonate 1986 50 1ndash10
31 Kalia yn nonata lB lund CH guy RH Development of skin
barrier function in premature infants J Invest Dermatol 1998 111
320ndash326
32 Kjartansson S arsan S Hammarlund K Sjoumlrs g Sedin g Water loss
from the skin of term and preterm infants nursed under a radiant
heater Pediatr Res 1995 37 233ndash238
33 mok Q Bass Ca Ducker Da mcintosh n temperature instability
during nursing procedures in preterm neonates Arch Dis Child
1991 66 783ndash786
34 mancini aJ Sookdeo-Drost S madison KC Smoller BR lane at
Semipermeable dressings improve epidermal barrier function in
premature infants Pediatr Res 1994 36 306ndash314
35 Donahue ml phelps Dl Richter Se Davis Jm a semipermeable skin
dressing for extremely low birth weight infants J Perinatol 1996 16
20ndash26
36 nopper aJ Horii Ka Sookdeo-Drost S Wang tH mancini aJ lane at
topical ointment therapy benefits premature infants J Pediatr 1996
128 660ndash669
37 pabst RC Starr Kp Qaiyumi S Schwalbe RS gewold iH the effect
of application of aquaphor on skin condition fluid requirements
and bacterial colonization in very low birth weight infants
J Perinatol 1999 19 278ndash283
38 Kjartansson S Hammarlund K Sedin g insensible water loss from
the skin during phototherapy in term and preterm infants Acta
Paediatr 1992 81 764ndash768
39 grunhagen DJ de Boer mg de Beaufort aJ Walther FJ
transepidermal water loss during halogen spotlight phototherapy in
preterm infants Pediatr Res 2002 51 402ndash405
40 Hanley K Jiand y elias pm Feingold KR Williams ml acceleration
of barrier ontogenesis in vitro through air exposure Pediatr Res
1997 41 293ndash299
41 Denda m Sato J masuda y et al exposure to a dry environment
enhances epidermal permeability barrier function J Invest Dermatol
1998 111 858ndash863
9 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
42 Aringgren J Sjoumlrs g Sedin g ambient humidity influences the rate of
skin barrier maturation in extremely preterm infants J Pediatr 2006
148 613ndash617
43 Sinclair l Sinn J Higher versus lower humidity for the prevention of
morbidity and mortality in preterm infants in incubators (protocol)
Cochrane Database Syst Rev 2007 issue 2 art noCD006472
doi10100214651858
44 Hey en Katz g the optimum thermal environment for naked
babies Arch Dis Child 1970 45 328ndash334
45 Sauer pJJ Dane HJ Visser HKa new standards for neutral thermal
environment of healthy very low birthweight infants in week one of
life Arch Dis Child 1984 59 18ndash22
46 Dollberg S Xi y Donnelly mm a noninvasive alternative to rectal
thermometry for continuous measurement of core temperature in
the piglet Pediatr Res 1993 34 512ndash517
47 messaritakis J anagnostakis D laskari H Katerelos C Rectal-skin
temperature difference in septicaemic newborn infants Arch Dis
Child 1990 65 380ndash382
paeDiatRiCS anD CHilD HealtH 184 16
Practice points
bull Hypothermia in the newborn infant is associated with adverse
outcome
bull Despite improvements in technology the preterm baby is still
at high risk of hypothermia immediately after delivery
bull prevention of evaporative heat losses eliminates hypothermia
at resuscitation
bull High evaporative fluid losses must be prevented if the baby
is nursed under a radiant heater
bull more studies are needed to determine the optimum
management after delivery and to show if reducing
transepidermal water loss has an effect on the rate of skin
maturation
bull Continuous monitoring and display of a central and peripheral
temperature gives early warning of developing cold stress
0 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemiaJ m Hawdon
Abstractat birth the newborn baby undergoes many adaptive changes to inde-
pendent extrauterine life these include the changes of metabolic adap-
tation which must be understood in order to identify and manage the
conditions in which metabolic adaptation is delayed impaired or fails
resulting in low levels of glucose and other metabolic fuels which in turn
affect neonatal neurological function and if prolonged and severe cause
potential adverse outcome Babies identified as at risk of impaired met-
abolic adaptation must undergo clinical monitoring including accurate
blood glucose monitoring tailored to their condition Babies who present
with abnormal clinical signs in association with a low blood glucose level
must be investigated for underlying cause and treated promptly preven-
tion and treatment of clinically significant hypoglycaemia must be planned
to avoid compromising successful establishment of breast feeding
Keywords alternative fuels blood glucose breast feeding neonatal
metabolic adaptation operational thresholds risk factors
Introduction
At birth the newborn baby undergoes many adaptive changes to independent extrauterine life These include the changes of met-abolic adaptation essential to ensure energy provision to vital organs and then to sustain growth and further development The changes involved in metabolic adaptation must be understood in order to identify and manage the conditions in which metabolic adaptation is delayed impaired or fails The clinical outcome of these circumstances is usually referred to with the single short-hand diagnostic term lsquoneonatal hypoglycaemiarsquo However as will be illustrated in this article it is not appropriate to ascribe a diagnostic label to neonatal hypoglycaemia first because glucose is not the only fuel in the neonatersquos fuel economy and second because hypoglycaemia is the consequence of a number of vari-ous underlying disorders and thus does not in itself warrant a diagnostic label
There have been extensive studies of metabolic adaptation in human neonates and neonatal non-human mammals The latter studies have identified those mammals most similar to humans
J M Hawdon MA MBBS MRCP FRCPCH PhD is Consultant Neonatologist and
Honorary Senior Lecturer at UCL EGA Institute for Womenrsquos Health
Elizabeth Garrett Anderson and Obstetric Hospital University College
London Hospitals NHS Foundation Trust Huntley Street London UK
paeDiatRiCS anD CHilD HealtH 184 161
in terms of metabolic adaptation and sought to compare nutri-tionally comparable time frames eg suckling versus weaning periods Whilst the processes of metabolic adaptation are well described in term and preterm human neonates there are few if any clinical studies in human neonates of sufficient rigour to provide evidence for the circumstances in which brain injury may occur and thus it is not possible to provide evidence-based guide-lines for the prevention and management of clinically significant hypoglycaemia Therefore recommendations in this article and in the referenced review articles by recognized experts remain pragmatic and urge clinicians to individualize management for each baby placing heavy emphasis on careful clinical evaluation rather than single numerical definitions of brain-injuring hypogly-caemia and on detecting and treating underlying pathologies1ndash6
Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
During intrauterine life the fetus receives via the placenta a con-stant supply of nutrients initially for growth but in the third tri-mester also for storage Glucose crosses the healthy placenta at a rate of approximately 5 mgkgmin In addition to that required for basal fetal metabolism glucose is converted to glycogen which is stored in the liver cardiac muscle and central nervous system In the third trimester excess glucose is converted to tri-glycerides which are stored in adipose tissue
Insulin is an important fetal hormone to ensure glucose and other substrates are utilized for growth and storage but in nor-mal circumstances insulin is not required for fetal glucose con-trol The exception is for the infant of the mother with poorly controlled diabetes when transfer of glucose across the placenta is at a higher rate driven by the maternalndashfetal concentration gra-dient This results in increased insulin secretion excess growth and increased storage of glycogen and adipose tissue (macroso-mia) along with increased risk of intracellular hypoxia
Conversely in the fetus affected by severe placental insuffi-ciency transfer of glucose and other nutrients across the placenta is at a lower rate and the fetus is required to metabolize first its own fuel stores and then structural proteins (eg in muscle) to ensure energy delivery to the vital organs assisted by the redis-tribution of blood flow to these organs Should placental function deteriorate further these adaptive responses fail Fetal hypogly-caemia has been described in these circumstances78
When placental nutrition abruptly ceases at birth the healthy neonate is dependent upon endocrine changes to initiate meta-bolic adaptation Insulin levels fall steadily and the action of any residual circulating insulin is overcome by the surge of the coun-ter-regulatory hormones glucagon and the catecholamines This change in the balance of glucoregulatory hormones induces the activity of key enzymes for glycogenolysis (release of glucose from glycogen stores) gluconeogenesis (production of glucose from precursors including glycerol and amino acids) lipolysis (release of free fatty acids and glycerol from adipose tissue stores) and beta-oxidation of fatty acids to produce ketone bodies910 If fasting is prolonged structural protein is broken down to release gluconeogenic amino acids Other than lipolysis and proteolysis all of these processes take place in the liver Glycogenolysis also takes place in cardiac muscle and the central nervous system providing immediate energy (in the form of glucose or lactate)
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
at this crucial time411 Clearly during this catabolic phase of immediate postnatal nutrition prior to the establishment of suck-ling feeds provision of energy for vital organ function is at the expense of growth and fuel storage
The postnatal metabolic transition is characterized by low cir-culating blood glucose concentrations compared to those of older infants and children often for a number of days12 This is almost always of no pathological significance for a number of reasons including differences in the function and metabolic requirements of the brain and importantly the production and utilization of alter-native fuels lactate and ketone bodies which are in plentiful supply in the neonate341213ndash20 An important finding from clinical studies and of clinical relevance to those caring for mothers and babies is that in all groups of infants studied to date those who are breast fed have higher circulating ketone body levels than those who are formula fed even after correcting for blood glucose levels102122
There are circumstances however when hypoglycaemia is severe and prolonged and conditions when alternative fuel pro-duction is also impaired or fails In these circumstances low blood glucose levels do acquire clinical significance The key metabolic processes and the risk factors for impaired metabolic adaptation are summarized in Table 1
Metabolic changes at birth ndash key hormones and metabolic processes and risk factors for impaired metabolic adaptation
Postnatal metabolic
changes
Risk factors
Hormones
insulin falls neonatal hyperinsulinism ndash infant of
diabetic mother or idiopathic
glucagon surge possibly blunted by iv glucose or
formula feeds
Catecholamine surge maternal beta-blocker medication
(Cortisol ndash weak effect) (pituitary or adrenal insufficiency)
Metabolic processes
glygogenolysis preterm intrauterine growth
restriction (iugR) ndash reduced stores
perinatal hypoxia-ischaemia ndash stores
utilized
Hyperinsulinism
maternal beta-blocker medication
glycogen storage disorders
gluconeogenesis Hyperinsulinism
maternal beta-blocker medication
Hepatic dysfunction
Very rare inborn errors of metabolism
lipolysis preterm iugR ndash reduced stores
Hyperinsulinism
maternal beta-blocker medication
Ketogenesis Defects of beta-oxidation of fatty
acids
Hepatic dysfunction
Table 1
paeDiatRiCS anD CHilD HealtH 184 16
Impaired metabolic adaptation
Risk factors for impaired metabolic adaptation vary and may be related to any of the following reduced body fuel stores failure of the normal endocrine changes at birth systemic illnesses which impede function of the liver where the key metabolic processes occur or rarely inborn errors of metabolism (see Table 1)
It is well recognized that significant hypoglycaemia will result in a reduced level of consciousness andor fits However it is always important to be alert for detect and treat an underlying pathology which could be causing both the hypoglycaemia and the abnormal signs Often abnormal signs and hypoglycaemia are co-morbidities eg a primary neurological problem causes both abnormal neurological signs and hypoglycaemia secondary to poor feeding For this reason all possible underlying causes for presentation with hypoglycaemia must be considered and investigations planned accordingly Investigations for inborn errors of metabolism and endocrine disorders are most informa-tive if carried out when blood glucose levels are low
There have been extensive efforts to use data from clinical stud-ies of the human neonate to determine the significance of neonatal hypoglycaemia in terms of neurophysiological neurodevelopmental and neuroradiological sequelae However there are major difficul-ties in interpreting these clinical studies as to date these have been flawed by confounding factors such as immaturity placental insuf-ficiency and co-existing complications by heterogeneity of subjects and by failure to take into account protective mechanisms11423 The evidence from both animal and human studies suggests lsquopurersquo hypo-glycaemic brain injury is rare and for hypoglycaemic brain injury to occur there must be co-existing failure of metabolic adaptation such that alternative fuels are not available There is no evidence that lsquotransitionalrsquo hypoglycaemia in the healthy neonate is associated with acute or long term sequelae and indeed even for babies in the at-risk groups on many occasions protective factors will prevail
Diagnosis of clinically significant hypoglycaemia
lsquoNeonatal hypoglycaemiarsquo is a commonly cited diagnosis most often based on a single blood glucose level and using inaccurate methods of measurement and with disregard for the presence or absence of associated clinical signs In the many published texts and local guidelines there is no consistency of approach For this reason a multinational group of experts attempted to examine critically the evidence on which clinical recommendations should be made1 Fol-lowing detailed analysis the authors considered it impossible to define hypoglycaemia as a single blood glucose level and instead suggested operational thresholds and therapeutic goals They con-cluded that low blood glucose levels accompanied by neurological signs should be investigated and treated regardless of the blood glu-cose level They also pragmatically concluded that a blood glucose level below 10 mmollitre should be treated immediately In babies who are at risk of impaired metabolic adaptation but who have no clinical signs it is recommended that interventions to raise blood glucose level are considered if blood glucose levels are persistently below 20 mmollitre For sick and very low birthweight babies who are likely to have a requirement for intravenous glucose there should be a lsquotherapeutic goalrsquo to maintain blood glucose levels above 25 mmollitre Where there is known hyperinsulinism (a very high-risk condition characterized by high intravenous glucose
2 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
requirements to maintain normoglycaemia) an operational thresh-old and therapeutic goal of 35 mmollitre has been proposed24
Finally there must be careful consideration of the infant of the diabetic mother In extreme and rare cases there may be signifi-cant but transient hyperinsulinism and in these cases the thera-peutic goal must be 35 mmollitre More commonly babies whose mothersrsquo diabetes has been well controlled will have normal lsquotran-sitional hypoglycaemiarsquo or slightly delayed metabolic adaptation while insulin levels fall postnatally There must be careful and repeated clinical assessment including blood glucose monitoring For infants of diabetic mothers who have no evidence of signifi-cant hyperinsulinism and no abnormal clinical signs there is no evidence that the operational threshold for hyperinsulinism must be applied Indeed to do so would result in separation of large numbers of healthy babies from their mothers with the conse-quent impact upon breast feeding and resource allocation25
The operational thresholds for various groups of babies are summarized in Table 2
The guidance relating to operational thresholds is predicated upon the accurate measurement of blood glucose levels It is now well known that the commonly used reagent strips are insufficiently accurate to diagnose hypoglycaemia and monitor at-risk infants and there must be access to equipment which allows immediate and accurate determination of blood glucose levels1426ndash28
Blood glucose monitoring
An accurate method for blood glucose monitoring must be employed as described above The sample should be free flowing venous or from a warm heel such that the blood flows freely without squeezing
Blood of high haematocrit often yields low blood glucose lev-els because of dilution of glucose by red cell water However this is also clinically relevant because polycythaemia is itself a high-risk situation Therefore in polycythaemic infants both the haematocrit and blood glucose level must be monitored and both acted upon accordingly
Operational thresholds for blood glucose levels in the management of babies at risk of impaired metabolic adaptation124
Clinical condition Blood glucose level at which
to consider intervention and
therapeutic goal
all at-risk babies lt10 mmollitre
abnormal neurological
signs
intervene regardless of blood
glucose levelSystematically unwell baby therapeutic goal of 25 mmollitre
at-risk babies no abnormal
neurological signs
persistently lt20 mmollitre
Hyperinsulinism 35 mmollitre
Table 2
paeDiatRiCS anD CHilD HealtH 184 163
Only babies in at-risk groups or babies who have abnormal neurological signs should be subjected to blood glucose monitor-ing (Table 3)
It is important not to commence blood glucose monitoring too soon after birth as to do so would fail to differentiate the baby with incipient hypoglycaemia from the baby undergoing the nor-mal postnatal fall in blood glucose level It is recommended in the otherwise healthy but at-risk baby to wait until around 3 h after birth to make the first blood glucose estimation2528 In prac-tice this is usually before the second feed assuming best practice of offering a baby a breast (or if necessary formula feed) imme-diately after birth Clearly if the baby is unwell or has abnormal clinical signs in the first 3 h they will be treated according to clinical condition which will include intravenous fluids and the therapeutic goal described above would apply
Similarly the temptation to measure blood glucose level shortly (within 2 h) after intravenous glucose has been discon-tinued must be avoided In this circumstance as at birth blood glucose levels fall and then subsequently rise in response to coun-ter-regulation It is this effective rise which must be assessed by blood glucose measurement at least 2 h after a change is made (provided the baby remains clinically well)
Blood glucose levels rise after a feed and fall to a nadir before the subsequent feed As our concern is the lowest blood glucose level during the feed cycle and as this measurement may assist in determining best feed frequency it is important that pre-feed blood glucose concentration is measured There is no clinical value in measuring a post-feed blood glucose level as this may be falsely reassuring and this practice subjects babies to more frequent heel pricks or venesections than is necessary
Finally consideration must be given to when to discontinue blood glucose monitoring This will depend upon the babyrsquos clin-ical condition feeding pattern and underlying disorder or risk factors for impaired metabolic adaptation
Prevention and management of clinically significant hypoglycaemia
In babies at risk of clinically significant hypoglycaemia and who are well enough to tolerate enteral feeds milk feeds are the
At-risk babies for whom blood glucose monitoring is recommended
abnormal neurological signs
Systemically unwell eg suspected or proven infection
hypoxicndashischaemic encephalopathy
preterm (lt 37 weeks)
intrauterine growth restriction (lt 2nd centile and any baby with
signs of wasting)
infant of diabetic mother
polycythaemia
maternal beta-blocker medication
Suspected hyperinsulinism
Suspected inborn error of metabolism or endocrine disorder
Table 3
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
mainstay of prevention For babies who are able to feed orally breast feeding should be first choice and there must be maximal support for the mother to do so This is a key clinical priority for midwives and paediatricians
If there are concerns regarding adequacy of breast feeding to prevent hypoglycaemia the mother should be encouraged to commence expression of milk from very soon after birth If there is insufficient breast milk to prevent babies reaching the opera-tional thresholds described above there should be judicious use of formula milk using only the smallest amount required to keep the babyrsquos glucose in the required range Formula milk in exces-sive quantities has been demonstrated to suppress normal meta-bolic adaptation2122
In babies for whom early enteral feeds are not appropriate or not tolerated or for whom enteral feeding does not prevent blood glucose level falling below operational thresholds intravenous glucose infusion at rates around 4ndash5 mgkgmin (58ndash72 mlkgd of 10 dextrose) are usually sufficient to prevent hypoglycae-mia If blood glucose levels remain below therapeutic goals the rate of infusion may be steadily increased Excess glucose infu-sion over and above that required to maintain the therapeutic goal will stimulate insulin and there is a risk of rebound hypo-glycaemia if high rate glucose infusions are too rapidly reduced Milk feeds if tolerated should be continued if intravenous glu-cose is commenced
If infused volume of glucose solution becomes excessive in order to maintain therapeutic goals or if fluid restriction must be applied more concentrated glucose concentrations must be infused through a central venous line This is particularly rel-evant to the hyperinsulinaemic baby in whom glucose infusion rates in excess of 8ndash10 mgkgmin are required to maintain ther-apeutic goals There is a high risk of severe and brain-damaging hypoglycaemia if treatment is delayed or fails to raise blood glu-cose levels and management of these babies requires consulta-tion with or referral to a specialist centre24
If there is presentation of hypoglycaemia with abnormal clinical signs or a very low blood glucose level (less than 1 mmollitre) this mandates urgent treatment with intravenous glucose The rates of glucose infusion described above are usually sufficient to bring the blood glucose level rapidly to the therapeutic goal without a bolus of glucose being necessary In fact a bolus dose of glucose will result in a peak blood glucose level and then an insulin surge making subsequent management problematical This is minimized by the use of a lsquomini-bolusrsquo should a bolus of glucose be required ndash 200 mg glucosekg (2 mlkg of 10 dextrose)28 Indications for mini-bolus are infants presenting with fits or coma or an lsquounre-cordablersquo or zero blood glucose level A mini-bolus should always be followed with glucose infusion or an increased glucose infusion rate if a baby already receiving intravenous glucose has required a mini-bolus
The temptation to supplement enteral feeds with glucose polymers and energy supplements (eg Duocal) or to use oral glucose gels or solutions (eg Hypostop) should be avoided as this carries a risk of necrotizing enterocolitis is likely to suppress normal metabolic adaptation and will suppress the appetite of the baby for effective oral feeding
Finally there are additional medications which may be employed in specific circumstances (Table 4) More detailed descriptions are given elsewhere242728 Babies who have hypoglycaemia which
paeDiatRiCS anD CHilD HealtH 184 164
is difficult to control by the measures described above and who require these additional treatments should be cared for in a centre which has expertise in metabolic and endocrinological conditions
Summary
Much controversy and confusion has surrounded neonatal hypo-glycaemia but this usually arises as a result of failure to under-stand the processes of normal metabolic adaptation and the fact that hypoglycaemia is a presenting sign rather than a diagnosis in itself Plans for investigation and management must be based upon the most likely underlying cause of impaired metabolic adaptation and take into account the clinical condition of the baby This is counter to the current trend to propose rigid pro-tocols and algorithms and re-introduces the value of detailed clinical evaluation and decision making The mainstay of man-agement is close clinical observation of vulnerable infants and energy provision tailored to their individual needs whilst avoid-ing excessively invasive management (namely unnecessary sep-aration of mother and baby routine or excessive formula milk supplementation or intravenous glucose administration) which themselves inhibit protective metabolic responses and impede successful establishment of breast feeding
ReFeRenCeS
1 Cornblath m Hawdon Jm Williams aF et al Controversies regarding
definition of neonatal hypoglycemia Suggested operational
thresholds Pediatrics 2000 105 1141ndash1145
2 Cornblath m ichord R Hypoglycemia in the neonate Semin
Perinatol 2000 24 136ndash149
3 Vannucci RC Vannucci SJ Hypoglycaemic brain injury Semin
Neonatol 2001 6 147ndash155
4 Rozance pJ Hay WW Hypoglycaemia in newborn infants features
associated with adverse outcomes Biol Neonate 2006 90 74ndash86
5 Hawdon Jm Hypoglycaemia in newborn infants defining the
features associated with adverse outcomes ndash a challenging remit
Biol Neonate 2006 90 87ndash88
6 Williams aF neonatal hypoglycaemia clinical and legal aspects
Semin Fetal Neonatal Med 2005 10 363ndash368
7 Soothill pW nicolaides KH Campbell S prenatal asphyxia
hyperlacticaemia hypoglycaemia and erythroblastosis in growth
retarded fetuses BMJ 1987 294 1051ndash1053
Additional medication in specific conditions (if these are required there must also be referral to a specialist centre)
Medication Indication
glucagon intramuscular bolus dose of 200 μgkg
transient rise in blood glucose level eg
when difficulty re-siting intravenous infusion
Diazoxide Hyperinsulinism
Hydorcortisone pituitary or adrenal insufficiency
Table 4
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
8 Hawdon Jm Ward platt mp mcphail S Cameron H Walkinshaw Sa
prediction of impaired metabolic adaptation by antenatal Doppler
studies in small for gestational age fetuses Arch Dis Child 1992
67 787ndash792
9 Deshpande S Hawdon Jm et al adaptation to extrauterine life in
Rodeck C Whittle m eds Fetal medicine Basic Science and Clinical
practice edinburgh Churchill livingstone 1999
10 Ward platt m Deshpande S metabolic adaptation at birth Semin
Fetal Neonatal Med 2005 10 341ndash350
11 eyre Ja Stuart ag Forsyth RJ Heaviside D Bartlett K glucose
export from the brain in man evidence for a role for astrocytic
glycogen as a reservoir of glucose for neural metabolism Brain Res
1994 28 349ndash352
12 Hawdon Jm Ward platt mp aynsley-green a patterns of metabolic
adaptation for preterm and term infants in the first neonatal week
Arch Dis Child 1992 67 357ndash365
13 Hawdon Jm Ward platt mp aynsley-green a prevention and
management of neonatal hypoglycaemia Arch Dis Child Fetal
Neonatal Ed 1994 70 F60ndash64
14 Hawdon Jm Hypoglycaemia and the neonatal brain Eur J Paediatr
1999 158 S9ndash12
15 massieu l Haces ml montiel t Hernaacutendez-Fonseca K acetoacetate
protects hippocampal neurons against glutamate-mediated neuronal
damage during glycolysis inhibition Neuroscience 2003 120
365ndash378
16 yamada Ka Rensing n thio ll Ketogenic diet reduces
hypoglycaemia-induced neuronal death in young rats Neurosci Lett
2005 385 210ndash214
17 nehlig a Brain uptake and metabolism of ketone bodies in animal
models Prostaglandins Leukot Essent Fatty Acids 2004 70
265ndash275
18 Hernaacutendez mJ Vannucci RC Salcedo a Brennan RW Cerebral blood
flow and metabolism during hypoglycemia in newborn dogs
J Neurochem 1980 35 622ndash628
19 Vannucci RC nardis ee Vannucci SJ Campbell pa Cerebral
carbohydrate and energy metabolism during hypoglycaemia in
newborn dogs Am J Physiol 1981 256 H1659ndashH1666
20 anwar m Vannucci RC autoradiographic determination of regional
cerebral blood flow during hypoglycaemia in newborn dogs Pediatr
Res 1988 24 41ndash45
21 Hawdon Jm Williams aF et al Formula supplements given to
healthy breastfed preterm babies inhibit postnatal metabolic
adaptation results of a randomised controlled trial Arch Dis Child
2000 82 a30
paeDiatRiCS anD CHilD HealtH 184 16
22 de Rooy l Hawdon Jm nutritional factors that affect the postnatal
metabolic adaptation of full-term small- and large-for gestational
age infants Pediatrics 2002 109 e42
23 Hawdon Jm Hypoglycaemia and brain injury ndash when neonatal
metabolic adaptation fails in levene m ed Fetal and neonatal
neurology and neurosurgery edinburgh Churchill livingstone in
press
24 Hussain K Congenital hyperinsulinism Semin Fetal Neonatal Med
2005 10 369ndash376
25 acolet D Diabetes in pregnancy Caring for the Baby after Birth
CemaCH 2007 2
26 Hussain K Sharief n the inaccuracy of venous and capillary blood
glucose measurement using reagent strips in the newborn period
and the effect of haematocrit Early Hum Dev 2000 57 111ndash121
27 Hawdon Jm Disorders of blood glucose homeostasis in the neonate
in Rennie Jm ed Robertonrsquos textbook of neonatology 4th edn
edinburgh Churchill livingstone 2005
28 Deshpande S Ward platt mp the investigation and management
of neonatal hypoglycaemia Semin Fetal Neonatal Med 2005 10
351ndash361
Practice points
bull identify risk factors for impaired metabolic adaptation
bull Clinical monitoring including accurate blood glucose
measurement for at-risk babies
bull Feed at-risk babies soon after birth and maintain thermal
homeostasis
bull take first blood glucose level at 3ndash4 h of age
bull intervene in at-risk baby with no clinical signs if two
consecutive blood glucose measurements lt 20 mmollitre
bull intervene in any baby with blood glucose measurement
lt 10 mmollitre
bull intervene in any baby with abnormal clinical signs regardless
of blood glucose level
bull investigate for underlying cause of failure of metabolic
adaptation
bull maintain lactation and breast feeding
5 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Resuscitation of the term and premature babyJonathan Wyllie
Abstractalthough most newly born babies establish normal respiration and
circulation without help up to 1minus2 may require some resuscitation
or stabilization Babies who do not establish adequate regular normal
breathing or who have a heart rate of less than 100 beatsmin or other
problems such as prematurity may require assistance the differences in
approach to the resuscitation of such babies originate in the physiology
and pathophysiology of acute asphyxia at birth However management
of airway and breathing remain the key features of resuscitation and
where cardiac depression has occurred this is nearly always due to hy-
poxia secondary to respiratory compromise therefore most babies will
respond within 2minus3 min of effective aeration of the lungs and the need
for intubation chest compressions or drugs is rare the international
liaison Committee on Resuscitation (ilCoR) evaluated evidence in 2000
and 2005 in order to provide guidelines for resuscitation they will do
so again for 2010 this evidence is limited in terms of both quantity and
quality and controversies still exist more research is needed to ensure
that our future actions are based upon evidence rather than history this
article will review the recommended approach to resuscitation as well as
some newer evidence
Keywords guidelines neonatal newborn premature resuscitation
Background
In the UK 669 601 babies were born alive in 2006 and most made the transition to extrauterine life without problems Those babies who did not establish adequate regular normal breathing or who had a heart rate of less than 100 beatsmin may have required assistance1 Factual evidence concerning the true requirement for resuscitation at birth is sparse Up to 10 of newborns may require some assistance to begin breathing with less than 1 needing extensive resuscitation2 However just because a baby received resuscitation does not necessarily mean that it was required and rates of intervention may be altered by educa-tion34 or the personnel present at deliveries5 In a UK tertiary centre with a standard approach to resuscitation at birth up to 12 of all babies received some airway assistance with just over 1 being intubated3 In Sweden only 1 of babies over 2500 g required mask or endotracheal tube ventilation at birth of which most responded to the former4
Jonathan Wyllie MBChB FRCPCH is Consultant Neonatologist at the James
Cook University Hospital Marton Road Middlesbrough TS4 3BW UK
paeDiatRiCS anD CHilD HealtH 184 16
Sometimes it is possible to predict babies who are likely to have respiratory depression at birth and to have appropriate per-sonnel present at delivery Guidelines for attendance at deliveries will vary with institution but even when almost 40 of deliv-eries are attended there may still be a further 15 of babies who require unexpected resuscitation5 a proportion that seems to remain whatever changes are made
The physiology of babies requiring help at birth has been summarized previously167 It allows a logical approach to resus-citation (Figure 1) when evidence is lacking and may prompt further research
Resuscitation at birth
PreparationAt birth resuscitation is more likely in babies with intrapartum evidence of significant fetal compromise those less than 35 weeksrsquo gestation those delivering vaginally by the breech and in multiple births Personnel trained in newborn resuscitation should be available at every delivery1 Someone experienced in tracheal intubation and advanced resuscitation should also be easily available for normal low-risk deliveries in hospital and ideally in attendance for deliveries with an increased likelihood of needing resuscitation In the latter cases the equipment and environment can be prepared beforehand including a discussion with the parents Wash your hands put on gloves and consider what help may be needed
Cord clampingAt birth it has long been known that delay in clamping the cord will lead to less anaemia in babies and reduce subsequent iron deficiency8 However few hospitals have practised this interven-tion due to worries about hypothermia and the need to resusci-tate or stabilize babies In developed countries the advantages seemed to be outweighed by the potential disadvantages A recent randomized controlled study of delayed clamping of the cord in premature babies found that the intervention group had less late-onset sepsis and fewer intraventricular haemorrhages9 This is a low-risk strategy which needs further evaluation in order to introduce it without increasing other risk factors in pre-mature deliveries
Assessment and temperature controlAssessment and temperature control for the newborn baby should occur at all deliveries The assessment indicates the need for resuscitation Babies may vary from 23 to 40+ weeksrsquo ges-tation and in weight from 500 to 5000 g They are born naked and wet and if left cannot cope with an environmental tem-perature of less than 32degC However if the term baby is imme-diately dried put skin-to-skin with the mother and covered the delivery room temperature can be as low as 25ndash28degC Obviously the smaller the baby the greater the surface area to mass ratio and the greater the risk of hypothermia Compromised babies are particularly vulnerable10 and hypothermia will lower oxygen tension11 increase metabolic acidosis12 and inhibit surfactant production13
An effective method of maintaining the temperature of prema-ture babies less than 28 weeksrsquo gestation is wrapping them with plastic before drying and then placing them under a radiant
6 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Dry the babyRemove any wet towels and cover
Start the clock or note the time
Give 5 inflation breathsLook for a response
If no increase in heart rate look for chest movement
Re-check head positionApply Jaw thrust
Repeat inflation breathsLook for a response
If no increase in heart rate look for chest movement
Try alternative airway opening manoeuvresRepeat inflation breaths
Look for a response
If no increase in heart rate look for chest movement
If the heart rate is not detectable or slow (lt60)Start compressions
3 compressions to each breath
Reassess heart rate every 30 secondsConsider venous access and drugs
Assess colour tone breathing and heart rate
Open the airway
If not breathing
If still not breathing
If no response
If still no response
When the chest is moving
If meconium present
Baby breathing wellDo not suction the airway
Baby floppy and not breathing wellConsider inspection and suction before
inflation breaths
Head in neutral position
Inflation breathsUse a well-fitting face mask
connedted to a
pressure-limited gas supply
Each breath 2ndash3 seconds
duration at 30 cm H2O for a
term baby
Get help from a second personto support the airway andor
inspect the oropharynx under
direct vision and consider
suction andor insert an
oropharyngeal airway
Chest compressionsCompvent ratio 31
Rate 120 events per minute
Ensure the chest moves with each ventilation breath
If breathingReassess heart rate and monitor baby
If heart rate is satisfactory but increasingContinue ventilation breaths at about 30 per
minute until baby is breathing adequately
If heart rate is satisfactory but increasingContinue ventilation breaths at about 30 per
minute until baby is breathing adequately
If heart rate is increasingStop compressions
Continue ventilation breaths at about 30 per
minute until baby is breathing adequately
If the chest is not movingRecheck head position and repeat inflation
breaths If competent consider intubation
If the chest is still not movingThe airway is the problem
Figure 1 newborn life support (Courtesy of the Resuscitation Council uK)
heater14 There is a small risk of hyperthermia so the temperature must be monitored carefully
An assessment is made of the babyrsquos colour tone respira-tions and heart rate127 The most important of these is heart rate and a stethoscope is more reliable than cord pulsation15 How-ever saturation monitors may offer a more reliable assessment of both heart rate and colour16 but their interpretation requires a detailed knowledge of normal saturations at birth at differing gestations A baby who is apnoeic and floppy in the absence of neurological disease is unconscious and likely to be in terminal apnoea however this does not change the initial approach other
paeDiatRiCS anD CHilD HealtH 184 167
than the need to summon help early APGAR scores are never calculated to guide resuscitation
Airway
If a baby is in primary apnoea then with an open airway the first gasp will start to aerate the lungs and most babies will be able to lsquoresuscitatersquo themselves as shown in physiological stud-ies on animals Neutral positioning of the babyrsquos head chin lift jaw thrust oropharyngeal airways and endotracheal intubation may all be helpful in certain situations if performed correctly17
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Endotracheal intubationThe placement of an endotracheal tube has long been the gold standard of airway control and this remains true in the unconscious baby if it is correctly sized placed and fixed in a timely manner However experience is directly related to effec-tiveness in endotracheal intubation1819 and the success rate of less experienced clinicians such as a resident (STA1-3) or a fel-low (STA3-5) is lower varying between 33 and 68 Even senior neonatologists often take longer than guidelines recom-mend19 Experienced clinicians may judge correct endotracheal position visually or by an increase in heart rate with the first breaths but detection of exhaled carbon dioxide will give more rapid confirmation in larger babies12171920 and this can be par-ticularly useful for less experienced clinicians or those supervis-ing them However not all systems for the detection of exhaled carbon dioxide work in the smallest premature infants
Laryngeal masksLaryngeal masks may be effective for ventilating term newborn babies but there are few data for small premature infants There have been reports of dislodged laryngeal airways during paedi-atric arrests when chest compressions have been administered Although success of placement at first attempt by paediatri-cians is greater with a laryngeal mask than with an endotra-cheal tube21 the only and small randomized controlled trial in the delivery room favoured endotracheal intubation when per-formed by an anaesthetist22 Based mainly upon case reports the laryngeal mask can be recommended when positioning and mask ventilation and endotracheal intubation have failed to secure the airway but not as yet as a primary method of airway control
MeconiumIn 2000 Wisewell et al23 reported a large randomized controlled trial showing that tracheal intubation and suctioning of meco-nium-stained but vigorous babies at birth did not reduce the incidence or severity of meconium aspiration syndrome More recently another randomized trial has now shown that suction-ing on the perineum similarly offers no benefit24 Neither of these practices is recommended but intubation and suction of meconium from the trachea of non-vigorous babies born through meconium-stained liquor is still recommended
Breathing
In the apnoeic baby the first breaths establish the resting lung volume and aerate the fluid-filled alveoli This mechanical effect aided by surface tension within the alveoli causes the initial fall in pulmonary vascular resistance Experimentally this effect occurs even if the lungs are ventilated with nitrogen but is increased when air is used presumably due to the vasodilator effect of 21 oxygen The mechanical stretching of the lung also triggers the activation of cyclo-oxygenase beginning the production of prostacyclin Bradykinin is produced which has a further direct vasodilator effect and also possibly via prostacyclin Therefore adequate airway control and passive ventilation is vital not only because babies requiring resuscitation at birth have an almost uniformly respiratory aetiology but also in order to promote post-natal adaptation and reverse any maladaptation
paeDiatRiCS anD CHilD HealtH 184 16
In term babies peak ventilatory pressures of 20ndash30 cmH2O may be required but the minimal pressure needed to achieve an improvement in heart rate should be used or if there is no response chest wall movement Longer breaths at lower pressure may be more effective in displacing alveolar fluid and establish-ing the resting lung volume in lungs with sufficient surfactant and may improve initial oxygenation However premature new-borns are obviously physiologically and anatomically less pre-pared for delivery than infants at term Over-inflation has been implicated in histological lung damage in animal models and high tidal volumes appear to be equally damaging whether given before or immediately after administration of surfactant How-ever the same effect is not seen if these excessive tidal volumes are delivered 15 min after administration of surfactant2526 It is now thought that both excess end expiratory volume and inad-equate end-expiratory volume may cause lung damage2728 In premature infants it would therefore seem sensible to use lower pressures of 20ndash25 cmH2O12 delivered in a controlled way to prevent over-inflation and to apply positive end-expiratory pres-sure (PEEP) to prevent damage from under-inflation PEEP also improves both lung compliance and gas exchange2930 Without PEEP the airways collapse during the expiratory phase in animal models of newborn resuscitation
If animal data can be extrapolated it would also seem appro-priate to give surfactant as soon as possible to premature babies in order to ameliorate damage2526
The majority of newborn infants requiring resuscitation will re-establish regular respiration after administration of a few breaths which may be due to Headrsquos paradoxical reflex by which the inflation triggers an inspiratory effort
VentilationOnce the lungs are aerated if the newborn remains apnoeic ventilation should be continued at 30ndash60 breathsmin avoiding hyperventilation and using the minimum pressure possible to maintain a heart rate greater than 100 beatsmin
Face mask the majority of infants who require ventilation receive it via a face mask This may be attached to a bagvalve system with a spring lsquoblow offrsquo system or a lsquoT-piecersquo with a set flow and pressure It is important to realize that the bagvalve system is flow sensitive and that the harder the operator presses the greater the flow and the higher the delivered pressure In fact 60 cmH2O can be achieved with vigorous squeezing of a self-inflating bag Therefore it may be advantageous that most opera-tors are unlikely to be as effective as they suppose in creating a seal with the mask31 This is a skill that requires tuition and prac-tice31 In delivering a set pressure T-piece systems such as the Tom Thumbcopy or Neopuffcopy perform better than any bagminusvalve system but require a gas supply There is no evidence that lung compliance can be assessed using any bag system
Continuous airway pressure case series have suggested that early or delivery room use of continuous positive airway pres-sure (CPAP) in premature babies may reduce chronic lung dis-ease There have been two randomized trials of which one was a pilot study The data from the COIN trial do not show any advan-tage other than a reduction in intubation and surfactant use in the intervention group However an excess of pneumothorax
8 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
was also reported The Vermont Oxford Network and the SUP-PORT trials will provide further data but at present the delivery room use of CPAP cannot be widely recommended and should be limited to those units experienced in its use or taking part in research
Air or oxygen oxygen has been in widespread use for resuscita-tion at birth since the 1930s and even hyperbaric oxygen was seriously supported in the 1960s For many years there have been concerns about tissue damage from oxygen deprivation during and after resuscitation It became evident in the 1950s that unrestricted oxygen therapy could have serious conse-quences for future vision More recently concerns have been raised about potential adverse effects on respiratory physiology cerebral circulation and tissue damage from oxygen free radicals even during resuscitation A meta-analysis of four human studies demonstrated a reduction in mortality and no evidence of harm in infants resuscitated in air versus 100 oxygen3233 However there are several significant methodological concerns with these studies and the results should be interpreted with caution There is insufficient evidence to recommend any specific concentration of oxygen to be used for newborn resuscitation Monitoring the oxygen saturation of babies may be helpful but as yet there are no time-related normal target ranges and healthy term babies may take up to 10 min to achieve preductal oxygen saturation of greater than 95 and up to 60 min to achieve this postductally
There is therefore equipoise which would be open to an appropriate randomized controlled trial In the meantime the evidence only supports use of either 21 or 100 oxygen It is provoking to realize that if air had been in constant use since the 1930s there would be insufficient evidence for use of supple-mental oxygen
Circulation
Early resuscitation (temperature control airway breathing) provides oxygenated blood in the pulmonary arterioles which if returned to the heart causes the rate to increase34 If due to acidosis and hypoxia the circulation is ineffective then chest compressions may be needed They should be commenced when the heart rate remains below 60min despite effective airway and breathing management127 The best technique is using two hands to encircle the chest1 A ratio of three compressions to one breath is internationally accepted127 but has no evidence to support it Research has shown that neither compressions nor drugs will work in this situation without oxygenated blood so effective lung aeration and ventilation is essential A logical approach would be to fill the alveoli with air and to compress the chest until they are empty However training and teamwork require an agreed ratio which has therefore not changed since guidelines were first agreed internationally Success is assessed by an increase in heart rate which should therefore be assessed every 30 s Compressions stop when the spontaneous heart rate is greater than 60 beatsmin
In hypoxic newborn animal models successful resuscitation can restore cardiac output and blood pressure to levels above baseline within 5ndash10 min However it should be noted that there is a decline to 30 lower than basal levels within 2 h and that blood pressure is relatively spared suggesting an even greater
paeDiatRiCS anD CHilD HealtH 184 16
reduction in tissue perfusion This should be considered in the later care of any neonate who was hypoxic at birth
Drugs
Neonatal bradycardia at birth is almost always due to hypoxia plusmn acidosis and therefore drugs are rarely needed Adrenaline (epi-nephrine) is reported as being used in between 1 and 4 babies per 2000 births which is a large variation in practice Reported success is also variable and must be interpreted in light of this variation The use of drugs in extremely premature infants is con-troversial Some data suggested good outcomes for babies below 28 weeksrsquo gestation given adrenaline but these were flawed by high numbers of babies receiving resuscitative drugs some before the airway had been appropriately managed Audit data now suggest a poor outcome such that many clinicians would now council against the use of adrenaline and other drugs to resuscitate extremely premature newborn babies
Adrenaline (epinephrine)In 2003 a Cochrane review of randomized controlled trials involv-ing adrenaline use for resuscitation of neonates was unable to identify a single clinical trial35 Despite the lack of human neo-natal data animal models show the potential of adrenaline in asphyxial cardiac arrest and it is reasonable to use it when ade-quate ventilation and chest compressions have failed to increase the heart rate above 60 beatsmin Use 10ndash30 μgkg intrave-nously and preferably via an umbilical venous line The tracheal route cannot be recommended but if used it is likely that doses within this range will be ineffective and 100 μgkg might be tried However the safety of such doses has not been studied
BicarbonateThe use of bicarbonate has long been controversial but many of the concerns relate to the rapid correction of acidosis in neonates after resuscitation or the routine use of bicarbonate infusion nei-ther of which can be advocated There are no published human neonatal data to support its use although some exist from animal studies Animal data have also shown that the binding of adren-aline to receptors in the myocardium is significantly impaired by lactic acidosis and recent work on human lymphocyte beta-adrenergic receptors supports this view Whether this is also true of the more important alpha receptors is unknown In practice reversing intracardiac acidosis may improve myocardial function and assist in achieving a return of spontaneous circulation 1ndash2 mmolkg of bicarbonate may be given but this remains a contro-versial area
VolumeVolume expansion should only be given when it is suspected that the baby has suffered blood loss or the infant appears to be in shock (pale poor perfusion weak pulse) and has not responded adequately to other resuscitative measures If there is no history suggestive of blood loss shock is most likely to be due to myo-cardial dysfunction in which case fluids should be administered cautiously The most logical replacement fluid would be blood but in its absence isotonic crystalloid rather than albumin is the solution of choice given in 10 mlkg aliquots and observing the response Three randomized trials in neonates have shown
9 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
isotonic crystalloid to be as effective as albumin for the treat-ment of hypotension but none has examined either the relative or actual effectiveness in resuscitation A recent blinded randomized study comparing normal saline albumin or no volume expansion in a normovolaemic asphyxiated neonatal animal model showed that volume expansion was not beneficial and made a number of parameters worse36
NaloxoneNaloxone is not recommended as part of the initial resuscita-tion of newborns with respiratory depression Before it is given supporting ventilation should have restored the heart rate and colour The dose is 100 μgkg intravenously or intramuscularly Tracheal administration cannot be recommended Although administration of naloxone to neonates who have been exposed to maternal opioids during labour is a practice of long-standing it lacks the proper evidence of efficacy
Non-response to resuscitation
There are few more frightening situations professionally than applying the correct interventions in resuscitating or stabilizing a baby and getting no response Each stage must be adequately performed before moving onto the next and this requires regular reassessment When experienced help is needed at a newborn resuscitation it is usually the airway and ventilation that require correction If the heart rate does not increase this usually means that the lungs have not been successfully aerated In some cases however it may mean that the heart cannot respond as the cir-culation is inadequate In this situation the only way to check that the lungs have been successfully aerated is to see the chest move with ventilation or to obtain evidence of ventilation from a detector of exhaled carbon dioxide If you do not see chest movement after another five breaths the most likely cause is an obstructed airway either due to incorrect positioning or because the jaw has not been drawn forwards An oropharyngeal airway can be very helpful at this point especially in the term baby Only very occasionally is the airway blocked by mucus vernix blood or meconium but if the airway is guaranteed and there is no heart rate response or chest movement this should be sought by direct suction of the trachea even in the absence of any meconium staining of liquor Pneumothoraces can occur spontaneously after delivery but are rare at resuscitation carried out with pressure-limited devices Equally rare are diaphragmatic hernias that have not been diagnosed antenatally giving problems at resuscitation
If the chest is moving but the heart rate has not responded to resuscitation consider rare possibilities such as fetal blood loss pneumothorax or heart block (mothers with undiagnosed systemic lupus erythematosis delivered for fetal bradycardia) as possibilities With adequate ventilation there is no evidence of oxygen concentrations less than 100 being responsible for prolonged bradycardia or failure to respond although current practice would support increasing the delivered oxygen concen-tration if resuscitation had been commenced using air
Outcome
The prognosis for the full-term baby subjected to sudden acute asphyxia is usually good provided the episode does not last for
paeDiatRiCS anD CHilD HealtH 184 17
long Most babies resuscitated from primary apnoea have no sequelae secondary to the resuscitation Many babies who start to breathe again regularly within 20 min of the circulation being restored recover completely but it is rare for a baby who is still gasping after 30 min to recover
The prognosis for the preterm baby of less than about 34 weeksrsquo gestation subjected to severe acute anoxia is less predict-able This is because of the risk of secondary intraventricular haemorrhage or periventricular intracerebral haemorrhage andor infarction after even a relatively brief asphyxial episode espe-cially in the period immediately around birth
The effects of chronic hypoxia are also difficult to predict but a reasonably clear idea of the extent of the problem should be obtainable within 36ndash48 h of the original chronic asphyxial insult A mild short-lasting state of hyperexcitability usually car-ries a good prognosis even if there is seizure activity but more severe symptoms can be associated with permanent handicap This is seen especially in infants with encephalopathy requiring ventilation
REFERENCEs
1 Biarent D Bingham R Richmond S et al european Resuscitation
Council guidelines for Resuscitation 2005 Section 6 paediatric life
support Resuscitation 2005 67(suppl 1) S97ndashS133
2 international liaison Committee on Resuscitation part 7 neonatal
resuscitation Resuscitation 2005 67 293ndash303
3 Singh J Santosh S Wyllie J mellon a effects of a course in
neonatal resuscitation - evaluation of an educational intervention
on the standard of neonatal resuscitation Resuscitation 2006 68
385ndash389
4 palme-Kilander C methods of resuscitation in low-apgar-score
newborn infants - a national survey Acta Paediatr 1992 81
739ndash744
5 Kroll l twohey l Daubeney p et al Risk factors at delivery and
the need for skilled resuscitation Eur J Obstet Gynecol Reprod Biol
1994 44 175ndash177
6 Wyllie Jp Resuscitation of the newborn The Foundation Years
2007 3(4) 153ndash157
7 Richmond S ed newborn life Support Resuscitation at Birth
london Resuscitation Council 2006
8 Ceriani Cernadas Jm Carroli g pelligrine l et al the effect of timing
of cord clamping on neonatal venous hematocrit values and clinical
outcome at term a randomized controlled trial Pediatrics 2006
117 e779ndashe786
9 mercer JS Vohr BR mcgrath mm padbury JF Wallach m oh W
Delayed cord clamping in very preterm infants reduces the incidence
of intraventricular hemorrhage and late-onset sepsis a randomized
controlled trial Pediatrics 2006 117 1235ndash1242
10 Dahm lS James lS newborn temperature and calculated heat loss
in the delivery room Pediatrics 1972 49 504ndash513
11 Stephenson J Du J tk o the effect of cooling on blood gas
tensions in newborn infants J Pediatr 1970 76 848ndash852
12 gandy gm adamsons Jr K Cunningham n Silverman Wa James lS
thermal environment and acid-base homeostasis in human infants
during the first few hours of life J Clin Invest 1964 43 751ndash758
13 gluck l Kulovich mV eidelman ai et al Biochemical development
of surface activity in mammalian lung pulmonary lecithin synthesis
0 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
in the human fetus and newborn and etiology of the respiratory
distress syndrome Pediatr Res 1972 6 81ndash99
14 Vohra S Roberts RS Zhang B Janes m Schmidt B Heat loss
prevention (Help) in the delivery room a randomised controlled
trial of polyethylene occlusive skin wrapping in very preterm infants
J Pediatr 2004 145 750ndash753
15 owen CJ Wyllie Jp Determination of heart rate in babies at birth
Resuscitation 2004 60 213ndash217
16 orsquoDonnell Cp Kamlin Co Davis pg Carlin JB morley CJ Clinical
assessment of infant colour at delivery Arch Dis Child Fetal
Neonatal Ed 2007 92 F465ndashF467
17 international liaison Committee on Resuscitation part 13 neonatal
Resuscitation guidelines Circulation 2005 112(suppl 24)
iV188ndashiV195
18 leone ta Rich W Finer nn neonatal intubation Success of
pediatric trainees J Pediatr 2005 146 638ndash641
19 orsquoDonnell Cp Kamlin Co Davis pg morley CJ endotracheal
intubation attempts during neonatal resuscitation success
rates duration and adverse effects Pediatrics 2006 117
e16ndash21
20 Repetto Je Donohue pa-CpK Baker SF Kelly l nogee lm use of
capnography in the delivery room for assessment of endotracheal
tube placement J Perinatol 2001 21 284ndash287
21 gandini D Brimacombe JR neonatal resuscitation with laryngeal
mask airway in normal and low birth weight infants Anesth Analg
1999 89 642ndash643
22 esmail n Saleh m ali a laryngeal mask airway versus endotracheal
intubation for apgar score improvement in neonatal resuscitation
Egypt J Anesthiol 2002 18 115ndash121
23 Wiswell te gannon Cm Jacob J et al Delivery room management
of the apparently vigorous meconium-stained neonate results of
the multicenter international collaborative trial Pediatrics 2000
105 1ndash7
24 Vain ne Szyld eg prudent lm Wisewell te aguilar am Vivas ni
oropharyngeal and nasopharyngeal suctioning of meconium-stained
neonates before delivery of their shoulders multicentre randomised
controlled trial Lancet 2004 364 597ndash602
25 Bjorklund lJ ingimarsson J Curstedt t larsson a Robertson B
Werner o lung recruitment at birth does not improve lung function
in immature lambs receiving surfactant Acta Anaes Scand 2001 45
986ndash993
26 Bjorklund lJ ingimarsson J Curstedt t et al manual ventilation
with a few large breaths at birth compromises the therapeutic effect
of subsequent surfactant replacement in immature lambs Pediatr
Res 1997 42 348ndash355
paeDiatRiCS anD CHilD HealtH 184 17
27 taskar V John J evander e Robertson B Jonson B Surfactant
dysfunction makes lungs vulnerable to repetitive collapse and re-
expansion Am J Respir Crit Care Med 1997 155 313ndash320
28 muscedere Jg mullen JB gan K Slutsky aS tidal ventilation at low
airway pressures can augment lung injury Am J Respir Crit Care Med
1994 149 1327ndash1334
29 nilsson R grossman g Robertson B Bronchiolar epithelial lesions
induced in the premature rabbit neonate by short periods of artificial
ventilation Acta Pathol Microbiol Scand 1980 88 359ndash367
30 probyn me Hooper SB Dargaville pa et al positive end expiratory
pressure during resuscitation of premature lambs rapidly improves
blood gases without adversely affecting arterial pressure Pediatr
Res 2004 56 198ndash204
31 Wood Fe morley CJ Dawson Ja et al improved techniques
reduce face mask leak during simulated neonatal resuscitation
study 2 Arch Dis Child Fetal Neonatal Ed in press doi101136
adc2007117788
32 tan a Schulz a orsquoDonnell CpF Davis pg air versus oxygen for
resuscitation of infants at birth Cochrane Database Syst Rev 2004
(3) CD002273
33 Davis pg tan a orsquoDonnell Cp Schulze a Resuscitation of newborn
infants with 100 oxygen or air a systematic review and meta-
analysis Lancet 2004 364 1329ndash1333
34 Dawes g Fetal and neonatal physiology Chicago year Book
publisher 1968 p 141ndash159
35 Ziino aJa Davies mW Davis pg epinephrine for the resuscitation
of apparently stillborn or extremely bradycardic newborn infants
Cochrane Database Syst Rev 2003 (2) CD003849
36 Wyckoff m garcia D margraf l perlman J laptook a Randomized
trial of volume infusion during resuscitation of asphyxiated neonatal
piglets Pediatr Res 2007 61 415ndash420
Practice points
bull Resuscitation at birth is different from that at all other times
of life
bull a standard approach can be applied to most newborn
resuscitation
bull guidelines are based on a rigorous evaluation of evidence
where possible
bull evidence is sparse but evolving
bull most preterm babies require stabilization rather than
resuscitation
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Acidndashbase physiology and blood gas interpretation in the neonateSusern tan
morag Campbell
Abstractacidndashbase balance describes the complex processes that work to main-
tain a stable extracellular pH for optimal cellular function the process
of balancing the production and neutralization of tissue acid provides a
great challenge for newborn infants who have significantly higher rates
of acid production than adults Factors which help maintain a stable
acidndashbase balance include buffers the respiratory system and renal sys-
tem Both intracellular and extracellular buffers resist changes in pH
the most important extracellular buffer system for maintaining stable
pH is the bicarbonate system in response to acidosis or alkalosis the
respiratory system balances the production of acid with the clearance
of Co2 by altering respiratory rate the kidneys provide a delayed but
sustained response to pH imbalance by excreting either acidic or alkaline
urine in response to systemic acidosis and alkalosis respectively in sick
premature infants these systems have a limited capacity completely to
control pH this review discusses the physiology of the three systems
which control acidndashbase balance patterns of clinical abnormalities in
acidndashbase status and their underlying causes are discussed We present
a systematic approach to blood gas analysis and interpretation in new-
born infants
Keywords acidosis alkalosis bicarbonate bloodndashgas analysis
metabolic pH
Introduction
Blood gas analysis is a routine procedure performed on newborn babies receiving respiratory support in the neonatal intensive care The combination of invasive and non-invasive assessment of ventilation and oxygenation enables clinicians appropriately to modify respiratory care according to each individual babyrsquos rapidly changing clinical status
Understanding the fundamentals of acidndashbase balance helps us to use blood gas analysis not only to assess respiratory sta-tus but also to provide information on metabolic status and the adequacy of tissue perfusion
Susern Tan MBBS MRCP is Clinical Fellow at the Neonatal Intensive Care
Unit 6th Floor North Wing St Thomasrsquo Hospital London SE1 7EH UK
Morag Campbell MBChB MRCP is Consultant Neonatologist at the
Neonatal Intensive Care Unit 6th Floor North Wing St Thomasrsquo
Hospital London SE1 7EH UK
paeDiatRiCS anD CHilD HealtH 184 17
What is understood by acid-base balance
Acidndashbase balance refers to the complex physiological processes used by the body to maintain a stable extracellular pH1 A serum pH within the range of 735ndash745 provides the ideal environment for cellular metabolism Maintaining a stable pH is critical as the metabolic activity of proteins is pH dependent and small changes in hydrogen ion (H+) concentration can potentially alter physio-logical function
Acids are substances that yield free H+ in solution while a base accepts H+ and in solution combines with an acid to neu-tralize it In the normal metabolic state H+ are continuously pro-duced and neutralized to maintain a steady pH balance12 The rate of H+ production is two to three times higher in neonates because of their rapid growth rates and increased acid production from protein turnover and bone mineralization The challenge of maintaining a stable pH through processing and neutralizing H+ is therefore greatest in newborn infants
Using exact values of H+ concentration to assess acidndashbase status is cumbersome and it is more commonly expressed as pH defined by the equation
pH = minuslog H+
Maintaining acidndashbase balance
The balance between production and excretion of acids in the body is controlled by buffer systems which have an immediate effect and by the respiratory and the renal systems
Buffer systemsBuffer solutions resist change in pH when acid or alkali is added due to their capacity to absorb or give up H+ The three main buffer systems in the body are the bicarbonate phosphate and protein systems1ndash3 The protein and phosphate buffer systems are intracellular and act as lsquosinksrsquo for extracellular H+ which are exchanged with intracellular potassium (K+) and sodium ions (Na+) In an acute metabolic acidosis hyperkalaemia may develop due to this H+ exchange4
The bicarbonate buffer system is extracellular and consists of a mixture of carbonic acid (H2CO3) and sodium bicarbon-ate (NaHCO3) This buffer system helps maintain a stable pH by soaking up excess H+ with HCO3
minus which in solution forms carbonic acid (H2CO3) Carbonic acid is a weak acid and readily dissociates to give CO2 which is transported in dissolved form to the lungs for excretion
H+ + HCO3minus harr H2CO3 harr H2O + CO2
The bicarbonate system therefore completes the neutraliza-tion of excess H+ and a stable plasma pH is maintained The relationships between pH HCO3
minus and CO2 in this system are described by the HendersonndashHasselbalch equation15
pH = 61 + log HCO3minus003 times CO2
where 61 is the log of the dissociation coefficient of carbonic acid and 003 the solubility of CO2 in plasma Buffers are most potent when there are equal amounts of H+ and HCO3
minus in solution The
2 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
bicarbonate system is not a potent buffer however as HCO3minus
and CO2 are readily altered by the body this system plays a very powerful role in pH homeostasis15
Respiratory regulationThe respiratory system adapts within minutes to hours as part of the acute response to acidosis This system modifies pH by balancing production of H+ with ventilatory clearance of CO2
H+ directly stimulates chemoreceptors in the respiratory cen-tre of the brainstem producing an increase in respiratory rate26 The response to respiratory acidosis is very rapid as CO2 easily diffuses across the bloodndashbrain barrier however in metabolic acidosis compensation is delayed until plasma bicarbonate fully equilibrates with cerebrospinal fluid (CSF) bicarbonate There is an inverse relationship between alveolar ventilation and partial pressure of dissolved carbon dioxide (PaCO2) a reduction in alveolar ventilation raises PaCO2 and decreases pH Changes in pH therefore affect alveolar ventilation and conversely changes in alveolar ventilation cause significant changes in pH
Renal regulationThe kidneys provide a delayed but sustained response to acidndashbase imbalances by excreting either acidic or alkaline urine In full-term and preterm babies the capacity for acid excretion and bicarbonate reabsorption is reduced as glomerular filtration rates are low and tubular function immature7 Renal function matures with gestation postnatal age and glucocorticoid and thyroid hormones78 Due to their limited capacity to preserve HCO3
minus newborn infants have lower serum bicarbonate levels and are predisposed to acidosis7
Bicarbonate is not effectively reabsorbed due to its size and electrical charge Instead intraluminal HCO3
minus combines with secreted H+ in tubular luminal fluid to produce carbonic acid which dissociates to give H2O and CO2 This CO2 diffuses into tubular cells combines with intracellular H2O and forms carbonic acid which liberates HCO3
minus and H+ HCO3minus is then
recovered to the circulation by exchange for chloride ions (Clminus) through the basal cell membrane247
Renal acid secretion occurs at all sites except the loop of Henle Primary active transport accounts for 5 and secondary for the remaining 95 of total H+ excretion Secondary trans-port involves an exchange between luminal Na+ and intracel-lular H+ Both ions bind to a membrane transport protein The Na+ concentration gradient between the tubular lumen and cells enables Na+ drag into the cell which generates energy to fuel active H+ excretion into the tubular lumen1ndash47
Quantifying acidosis
Standard base excess is a calculated value derived from PaCO2 and pH It is expressed as the mmollitre of base above or below normal buffer bases required to correct the pH to 74 at a PaCO2 of 40 mmHg A negative base excess or base deficit indicates an acidosis while a positive base excess indicates a relative alkalosis15
Anion gap is the measured difference between anions and cations in the blood
Anion gap = (Na+ + k+) minus (HCO3+Clminus)
paeDiatRiCS anD CHilD HealtH 184 17
Calculation of the anion gap enables clinicians better to define the underlying cause of a metabolic acidosis9 The common causes of an increased anion gap acidosis in neonates include lactic acidosis due to tissue hypoperfusion and hypoxia it may also be seen with certain inborn errors of metabolism and in uraemia910 The anion gap can help distinguish between the rela-tively benign non-anion gap hyperchloraemic acidosis seen in premature infants and a pathological lactic acidosis due to poor end-organ perfusion1011
Strong ion theory
Stewart described a complex acidndashbase model which proposed that H+ concentration results from the dissociation of water which is influenced by PaCO2 the strong ion difference and plasma weak acids12
Strong ions are ions that dissociate at normal body pH and include Na+ K+ and Clminus Weak acids in plasma which contrib-ute include albumin inorganic phosphate and plasma proteins their concentrations do not change with pH and are therefore a constant The effect of these factors and other unmeasured tissue ions on acidndashbase status can be quantified by the calculation of the strong ion gap (SIG)112 In the neonatal unit it is perhaps more important that we consider how principles of this model may relate to acidndashbase status rather than fully to quantify the SIG Theoretically low albumin and phosphate levels which fre-quently occur in premature infants by reducing the concentra-tion of weak acids can produce a relative alkalosis while high phosphate levels in renal failure may contribute to acidosis
Tissue oxygenation
Oxygenation is closely linked to acidndashbase status as optimal cel-lular function requires oxygen to fuel aerobic metabolism and produce energy In hypoxic conditions anaerobic metabolism predominates which is energy inefficient and results in a lactic acidosis1011
Tissue oxygen availability is related to regional blood flow haemoglobin level and haemoglobin oxygen affinity Arterial blood gases measure the partial pressure of dissolved oxygen (PaO2) which represents a small component of total oxygen con-tent the majority being transported bound to haemoglobin The relationship between percentage haemoglobin saturation (SaO2) and PaO2 is described by the sigmoidal oxyhaemoglobin disso-ciation curve which enables us to relate the two measures to each other235 The affinity of haemoglobin for oxygen is altered by local tissue factors Increases in temperature H+ PaCO2 and 23-diphosphoglycerate (DPG) levels shift the oxyhaemoglobin dissociation curve to the right reducing affinity for oxygen Decreases in temperature H+ PaCO2 and 23-DPG levels shift the curve to the left increasing oxygen affinity1ndash35 In the body haemoglobin oxygen affinity continuously changes increasing in the lungs to enable efficient oxygen uptake and decreasing at tissue level to provide efficient oxygen delivery to metabolically active tissues
Avoiding both hypoxia and hyperoxia is important in the neo-natal unit as deleterious effects of hypoxia are seen in infants with pulmonary hypertension1314 while hyperoxia is associated with an increased incidence of retinopathy of prematurity1516
3 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Clinical acidndashbase imbalances
Clinical acidndashbase imbalances can be respiratory metabolic or a mixture of both These abnormalities may be corrected by the acidndashbase regulatory mechanisms in the body in an attempt to maintain normal pH (Figure 1)
Respiratory acidosisThis occurs when any disorder leads to decreased alveolar ventilation Common causes of respiratory acidosis are listed in Table 1 Reduced respiratory clearance of CO2 means more dissolved CO2 accumulates in the plasma leading to increased production of carbonic acid and H+ Through chemoreceptor stimulation respiratory acidosis rapidly alters ventilation in an attempt to reduce CO226 Chemoreceptor mediated ventila-tory increases may only partly adjust in premature infants with underlying lung disease In babies with a sustained respiratory acidosis eg in chronic lung disease then metabolic compen-sation occurs through increased renal excretion of H+ and reabsorption of HCO3
minus slowly restoring pH to around 80 of normal47
paeDiatRiCS anD CHilD HealtH 184 17
The management of PaCO2 levels in infants receiving mechan-ical ventilation has important clinical implications Premature babies have impaired cerebral autoregulation17 and adverse neurological sequelae are reported in association with high PaCO2 levels18ndash20 Ventilation strategies which advocate lsquoper-missive hypercarbiarsquo have been developed to minimize airways damage from mechanical ventilation21 Published data suggest pulmonary benefits however the safe level of PaCO2 remains to be defined in premature infants2021
Respiratory alkalosisThis occurs when more CO2 is excreted than is produced by the body Pathological conditions leading to respiratory alkalosis are rare Hyperventilation in the neonatal setting is often iatrogenic or may be due to disorders in brainstem control of breathing including hypoxicndashischaemic encephalopathy or primary central nervous system abnormalities (see Table 1)
If respiratory alkalosis is sustained it may be compensated for by reduced reabsorption of filtered bicarbonate Reported adverse associations of low PaCO2 include periventricular leuco-malacia and intraventricular haemorrhage1922
K+
H+
Overventilation
CO2 + H2O harr H2CO3 harr H+ + HCO3ndash
Bicarbonate Buffer
Intracellular Buffer
uarr H+ excretionuarr HCO3
ndash absorption
uarr buffered H+
(NH4+ H2PO4
ndash)uarr ventilation rate
RespiratoryAcidosis
MetabolicAcidosis
darr CO2and uarr pH
RespiratoryAlkalosis
MetabolicAlkalosis
darr H+ anduarr pH
darr ventilation rate
uarrCO2
and darr pH
darr H+ excretiondarr HCO3
ndash absorption
uarrH+ and
darr pH
Brain
Brain
Intracellular Buffer
H+
K+
Sepsis
HypoxiaRDS
Metabolismand growth
Diuretics
Airwayobstruction
Neuromuscularproblems
IEM
Gastric losses
+ +
ndash -
Renal BufferRespiratory Buffer
Figure 1 mechanisms for regulation of extracellular pH iem inborn errors of metabolism RDS respiratory distress syndrome
4 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Common causes of acidndashbase imbalances
pH PCO2 H2CO3 Base excess Common neonatal causes
Respiratory acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
uarr normal normal bull upper airway obstruction choanal atresia
pierre-Robin sequence
bull lung abnormalities respiratory distress
syndrome transient tachypneoa of
newborn pneumonia meconium aspiration
syndrome pulmonary hypoplasia
congenital pulmonary malformations
bull Central hypoventilation hypoxic-ischaemic
encephalopathy intracranial haemorrhage
bull neuromuscular insufficiency congenital
myopathies congenital neuropathies
bull iatrogenic inadequate ventilatory settings
Compensated lower limit
of normal
uarr uarr gt+3
metabolic acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
normal darr ltminus3 increased anion gap
bull lactic acidosis sepsis hypoperfusion
shock necrotizing enterocolitis
bull inorganic acidosis inborn errors of
metabolism renal failure
normal anion gap
bull increased gastrointestinal H2Co3 losses
ileostomy diarrhoea
bull Renal tubular acidoses
Compensated lower limit
of normal
darr darr ltminus3
Respiratory alkalosis Uncompensated gt 745 darr normal normal bull iatrogenic excessive ventilatory settings
bull Compensatory hyperventilation hypoxic-
ischaemic encephalopathy
Compensated higher limit
of normal
darr darr ltminus3
metabolic alkalosis Uncompensated gt 745 normal uarr gt+3 bull gastric losses vomiting non-replacement
of excessive nasogastric aspirates
bull thiazide and loop diuretics
bull Hypokalaemia
Compensated higher limit
of normal
uarr uarr gt+3
Table 1
Metabolic acidosisThis frequently affects infants in the neonatal unit and has many causes1011 (see Table 1) There may be overproduction of tissue acid impaired acid clearance gastrointestinal loss of bicarbonate or an exogenous increased acid load eg chloride total paren-teral nutrition (TPN) or albumin1ndash323
Calculation of the anion gap to distinguish an increased anion gap acidosis from a non-anion gap acidosis is important both for treatment and prognosis1011 Acidosis stimulates respiratory compensation but this is limited in unstable infants Similarly renal compensation with improved HCO3
minus conservation is con-strained by tubular immaturity Treatment of the acidosis should be directed at the underlying cause eg hypoxia hypotension or excess Clminus rather than by administration of base
Metabolic alkalosisThis is unusual in neonates and is most frequently seen in infants with chronic lung disease or heart failure who are receiving diuretics Diuretics cause alkalosis by increasing renal fluid and Na+ losses An active process to reabsorb Na+ occurs in tubule cells which through enhanced H+ secretion and HCO3
minus reab-sorption produce alkalosis27
paeDiatRiCS anD CHilD HealtH 184 17
Metabolic alkalosis may also occur with excessive loss of gas-tric contents eg protracted vomiting or inadequate replacement of nasogastric aspirates (see Table 1)
Interpreting blood gases
Blood gas measurements can provide important diagnostic and prognostic information and a systematic approach to blood gas analysis is described in Table 2 The clinical management of infants with abnormal gases requires a good understanding of acidndashbase physiology and tissue oxygenation and an apprecia-tion of factors which may affect the reliability of samples
Arterial blood sampling is the gold standard however indwelling arterial catheters and arterial stab samples are usually restricted to infants who are critically ill or those who require sig-nificant ongoing intervention Gases are most frequently measured in capillary or venous samples which correlate well with arterial samples for PaCO2 pH and base excess in babies and children receiving intensive care These correlations however are not valid in infants with peripheral vasoconstriction and hypotension2324
Non-invasive monitoring techniques may enable us to reduce the frequency of blood gas sampling Transcutaneous monitoring
5 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
A systematic approach to blood gas analysis
1 Collect the relevant information
bull type of gas ndash capillary or arterial
bull Current respiratory support ndash document level
bull transcutaneous Co2 and Sao2 levels
bull Clarify no significant clinical events before sampling
2 pH accept a range between 730 and 745 in newborn
babies this is lower than in older children is there an
alkalosis (pH gt 745) or an acidosis (lt 730)
3 Co2 aim for a range between 45 and 65 kpa a paCo2 level
more than 65 kpa suggests inadequate alveolar ventilation
while less than 45 kpa suggests hyperventilation Correlate
values with non-invasive measures
4 o2 Can only be assessed from arterial gases aim for pao2
between 60 and 80 kpa Correlate results with pulse
oximetry levels
5 HCo3 and base excess normal HCo3 level is between 20 and
24 mmollitre and bases excess +3 to minus3
6 anion gap look at the anion gap and lactate to help identify
the cause of an acidosis normal lactate levels should be less
than 2 mmollitre
7 Respiratory or metabolic compensation look at the pH and
assess whether it is appropriate for the Co2 level or is there
evidence of compensation
8 interpret use both the clinical history and blood gas
findings to help you identify the primary problem aim your
management at treating the underlying cause
9 Reassess if clinical management changes have been made
repeat the blood gas after an appropriate time interval to
ensure improvement
Table 2
provides a highly accurate and reliable method for measuring PaCO2 through the skin it can however be technically difficult may cause tissue damage and is of limited reliability when peripheral perfusion is reduced25 Continuous end-tidal CO2 measurements correlate well with arterial CO2 values in patients with normal ventilation and perfusion however in babies with lung disease alveolar collapse small tidal volumes and rapid respiratory rates can make these measurements unreliable26 Despite its limitations transcutaneous monitoring provides the best method for CO2 trend monitoring in the neonatal intensive care unit (NICU)25
Oxygen saturation levels can be continuously measured non-invasively using pulse oximetry While oximetry is easy to perform and accurate on occasion SaO2 levels obtained may be unreliable when tissue perfusion is poor or with movement artefact SaO2 monitoring is highly sensitive at detecting hypoxia but is limited in detecting hyperoxia as at levels more than 90 small changes in SaO2 may result in unacceptably large increases in PaO227 It is therefore essential that SaO2 alarm limits are set for all neonates receiving respiratory support to detect hypoxia and prevent hyperoxia1627
Continuous non-invasive monitoring provides invaluable information when managing complex infants in the NICU but it does not replace the need for regular blood gas analysis
paeDiatRiCS anD CHilD HealtH 184 17
ReFeRenCeS
1 Kellum Ja Determinants of blood pH in health and disease
Crit Care 2000 4 6ndash14
2 Quigley R Baum m neonatal acid base balance and disturbances
Semin Perinatol 2004 28 97ndash102
3 Brouillette Rt Waxman DH evaluation of the newbornrsquos blood gas
status Clin Chem 1997 43 215ndash221
4 Chan JC acid-base disorders and the kidney Adv Pediatr 1983 30
401ndash471
5 Siggaard-andersen o the pH-log pCo2 blood acidndashbase nomogram
revised Scand J Lab Invest 1962 14 598ndash604
6 Saetta m mortola Jp interaction of hypoxic and hypercapnic stimuli
on breathing pattern in the newborn rat J Appl Physiol 1987 62
506ndash512
7 Baum m Quigley R postnatal renal development in Seldin DW
giebisch g eds the kidney physiology and pathophysiology new
york lippincott Williams and Wilkins 2000 p 703ndash726
8 ortiz la Quan a Weinberg a et al effect of prenatal
dexamethasone on rat renal development Kidney Int 2001 59
1663ndash1669
9 gabow pa Kaehny WD Fennessey pV goodman Si gross pa
Schrier RW Diagnostic importance of an increased serum anion gap
N Engl J Med 1980 303 854ndash858
10 lorenz Jm Kleinman li markarian K oliver m Fernandez J Serum
anion gap in the differential diagnosis of metabolic acidosis in
critically ill newborns J Pediatr 1999 135 751ndash755
11 Deshpande Sa platt mp association between blood lactate and
acid-base status and mortality in ventilated babies Arch Dis Child
1997 76 F15ndash20
12 Stewart pa modern quantitative acid-base chemistry Can J Physiol
Pharmacol 1983 61 1444ndash1461
13 Dakshinamurti S pathophysiologic mechanisms of persistent
pulmonary hypertension of the newborn Pediatr Pulmonol 2005
39 492ndash503
14 mourani pm ivy DD gao D abman SH pulmonary vascular
effects of inhaled nitric oxide and oxygen tension in
bronchopulmonary dysplasia Am J Respir Crit Care Med 2004
170 1006ndash1013
15 Deulofeut R Critz a adams-Chapman i Sola a avoiding hyperoxia
in infants le 1250 g is associated with improved short- and long-
term outcomes J Perinatol 2006 26 700ndash705
16 Chow lC Wright KW Sola a Can changes in clinical practice
decrease the incidence of severe retinopathy of prematurity in very
low birth weight infants Pediatrics 2003 111 339ndash345
17 Boylan gB young K panerai RB Rennie Jm evans DH Dynamic
cerebral autoregulation in sick newborn infants Pediatr Res 2000
48 12ndash17
18 Kaiser JR gauss CH pont mm Williams DK Hypercapnia during
the first 3 days of life is associated with severe intraventricular
hemorrhage in very low birth weight infants J Perinatol 2006 26
279ndash285
19 Fabres J Carlo Wa phillips V Howard g ambalavanan n Both
extremes of arterial carbon dioxide pressure and the magnitude of
fluctuations in arterial carbon dioxide pressure are associated with
severe intraventricular hemorrhage in preterm infants Pediatrics
2007 119 299ndash305
20 thome uH Carroll W Wu tJ et al outcome of extremely preterm
infants randomized at birth to different paCo2 targets during the
first seven days of life Biol Neonate 2006 90 218ndash225
6 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
21 Carlo Wa Stark aR Wright ll et al minimal ventilation to prevent
bronchopulmonary dysplasia in extremely-low-birth-weight infants
J Pediatr 2002 141 370ndash374
22 okumura a Hayakawa F Kato t et al Hypocarbia in preterm
infants with periventricular leukomalacia the relation between
hypocarbia and mechanical ventilation Pediatrics 2001 107
469ndash475
23 peters o Ryan S matthew l Cheng K lunn J Randomised
controlled trial of acetate in preterm neonates receiving parenteral
nutrition Arch Dis Child 1997 77 F12ndash15
24 yildizda D yapiciolu H yilmaz Hl Sertdemir y Correlation of
simultaneously obtained capillary venous and arterial blood gases
of patients in a paediatric intensive care unit Arch Dis Child 2004
89 176ndash180
25 aliwalas ll noble l nesbitt K et al agreement of carbon
dioxide levels measured by arterial transcutaneous and end tidal
methods in preterm infants 28 weeks gestation J Perinatol 2005
25 26ndash29
26 Hagerty JJ Kleinman me Zurakowski D et al accuracy of a new
low-flow sidestream capnography technology in newborns a pilot
study J Perinatol 2002 22 219ndash225
paeDiatRiCS anD CHilD HealtH 184 17
27 poets CF Wilken m Seidenberg J Southall Dp von der Hardt H
Reliability of a pulse oximeter in the detection of hyperoxemia
J Pediatr 1993 122 87ndash90
Practice points
bull a stable extracellular pH is important for optimal cellular
functioning
bull abnormalities in acidndashbase balance are regulated by buffer
systems and the respiratory and renal tract
bull maintaining a stable pH is challenging for newborn babies
due to their high rates of acid production and immature
regulatory mechanisms
bull arterial or capillary blood gases provide an effective way to
monitor acidndashbase balance in newborns
bull Blood gases should be analysed in a structured manner
assessing pH and then respiratory and metabolic components
bull the treatment of acidndashbase abnormalities should be directed
at the underlying problem not merely at correcting pH
7 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Recognition and management of neonatal seizuresmalcolm levene
AbstractSeizures are the most common major manifestation of central nervous
system dysfunction in the newborn there are many causes but perina-
tal asphyxia and haemorrhagicinfarction lesions account for about 75
there is now considerable evidence that frequent but short seizures in
the neonate affect subsequent neurodevelopmental outcome Studies
using eeg or modified continuous tracing of eeg activity (aeeg or CFm)
have shown that there is often electroconvulsive dissociation this re-
fers to poor correlation between electrical seizures and clinical seizures
Commonly used anticonvulsants appear to increase electroconvulsive
dissociation effective management of neonatal seizures has proved very
disappointing and less than 50 of seizures are abolished by first-line
anticonvulsant medication (phenobarbitone or phenytoin) Drugs such
as midazolam and lidocaine may further reduce seizures but require
more evaluation the challenge is to assess new and more effective anti-
convulsants which are themselves associated with little neurotoxicity
Keywords antiepileptic drugs eeg neonatal seizures neurodegeneration
Convulsions are the most common major neurological sign seen in newborn infants and their incidence estimated from large population studies is 26 per 1000 live births1 Premature infants are over four times more likely to have convulsions than full-term infants12 Neonatal status epilepticus (continuous seizure activity lasting 30 min or more) diagnosed clinically is rare and accounts for only 5 of infants with seizures1 although this is now recognized more frequently as the result of continuous EEG monitoring3
Neonatal convulsions are described as presenting in a num-ber of different ways and various seizure types can be seen in the same baby over a number of hours The frequencies of the various patterns of seizure activity are given in Table 1 In very premature babies and to a lesser extent in term infants minor movement abnormalities may be difficult to identify as subtle seizures These include lip smacking tongue thrusting mouth-ing pedalling type movements of the lower limbs or swimming movements of the arms Apnoea can be a common manifesta-tion of subtle seizures The signs can be protean and vary from baby to baby or even in the same baby Virtually any stereotypic
Malcolm Levene MD FMedSc FRCPCH FRCH is Professor and Head of
Department of Paediatrics and Child Health at University of Leeds Leeds
and Honorary Neonatologist at Leeds General Infirmary Leeds UK
paeDiatRiCS anD CHilD HealtH 184 178
movement may be a manifestation of a seizure disorder in the newborn
Aetiology
The more carefully the fitting baby is investigated the more likely it is that a cause for the seizures will be found A number of recent papers have described the aetiology of neonatal con-vulsions after extensive investigations14 Tekgul et al4 recently studied a consecutive group of full-term infants with evidence of neonatal convulsions (recognized both clinically and on EEG) and reported their outcome Table 2 summarizes these data as well as risk of moderate or severe disability for each causative factor Perinatal asphyxia is the commonest cause for convul-sions in term infants with haemorrhagic or ischaemic lesions also being common
Overall the prognosis for the group of term babies with con-vulsions was good 72 had a favourable outcome Where asphyxia (hypoxicndashischaemic insult) is the cause of neonatal convulsions the outcome is poor in 50 The prognosis for neonatal convulsions when they were due to arterial or cere-brovenous infarction or intracranial haemorrhage was generally good Individually inborn errors are a very rare cause of neo-natal convulsions but in view of the treatable nature of some of these it is essential that these be considered and investigated appropriately5
Patterns of seizure activity in the newborn
Movement pattern Frequency ()
Clonic 50
tonic 20
Subtle 10ndash35 depending on maturity
myoclonic 5
Table 1
Cause incidence and outcome of neonatal convulsions in term infants14
Aetiological factor Incidence () Poor outcome ()
asphyxia 38ndash40 50
Cerebral arteriovenous
infarction
20 0
intracranial haemorrhage 12ndash20 13
Congenital cerebral anomaly 5ndash10 100
Hypoglycaemiahypocalcaemia 3ndash19
infection 3ndash20
inborn error of metabolism 1
unknown cause 10ndash13 0
Refers to moderate and severe neurodevelopmental abnormalitynumbers too small to make meaningful predictions
Table 2
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Controversies in the clinical management of neonatal seizures
In recent years we have learnt much more about the neurobi-ology of seizures and their effect on the developing brain The neonatal brain is in a neurophysiologically hyperexcitable state compared to the more mature brain and therefore is more prone to seizure activity This is due largely to a relative excess of GABA neuroreceptors GABA receptors are usually inhibitory but in the immature brain they have a paradoxically excitatory effect This changes at about term in primates and with progressive develop-ment they adopt a neuroinhibitory role6
The propensity to seizures in the neonatal brain makes resolv-ing the balance of risks between continuing seizure activity on the one hand against potentially adverse effects of therapy on the other a very important equation Added to this is the problem of accurately diagnosing neonatal seizures and whether commonly used anticonvulsants are successful in controlling them
These conundrums can be posed as a series of challenging questions which are discussed below
Do neonatal convulsions cause brain injuryConvulsions are a sign of neurological compromise and may indi-cate significant underlying structural brain damage or biochemi-cal disturbance which may cause further brain damage in its own right There has been considerable debate about the scale of the disability that convulsions cause the immature brain over and above that due to the underlying cause Most of our knowledge comes from studies in rodents and these have provided some tentative answers to this question
Seizures in the mature brain lead to neuronal necrosis but studies in very young rat pups whose brain development is somewhat similar to full-term infants have shown that a series of five brief seizures on five successive days does not cause struc-tural neuronal damage but does produce morphological changes in hippocampal neurones and worryingly deficits in the rat learning and visual spatial memory function in adolescent and adult life7 A single prolonged neonatal convulsion in similarly immature rats does not produce any functional effects8 Others have shown that following priming of the neonatal rat brain by short seizures as described above a further insult comprising induction of status epilepticus in the same rats at an older age causes neuronal necrosis9 This has been referred to as the lsquotwo hit hypothesisrsquo10
A more specific question is does seizure activity in an already significantly compromised brain cause additional neuropathol-ogy Wirrell et al11 studied a series of immature rat pups with the induction of an hypoxicndashischaemic (asphyxial) insult fol-lowed by either chemically-induced fits or a control sham pro-cedure In the more severely asphyxiated animals the degree of brain damage was increased significantly in those that had the additional burden of induced seizures
In summary these studies show that the immature brain is more resistant to short frequent post-seizure damage than the mature brain but despite resulting in no loss of neuronal numbers the function of the brain is permanently affected in later life In the asphyxiated brain seizures appear to have an additional adverse effect on brain damage Furthermore the immature brain that has been lsquoprimedrsquo by early seizures is more
paeDiatRiCS anD CHilD HealtH 184 179
vulnerable to status epilepticus later in life It would appear from these data that frequent seizures in the human infant should be stopped and this begs the question as to whether currently used anticonvulsants effectively control neonatal seizures
Can we rely on clinical versus EEG diagnosis of neonatal convulsionsTraditionally the diagnosis of neonatal convulsions has been made by observation and description of the frequency of abnor-mal movements EEG has been technically difficult in the hostile electrical activity of a neonatal intensive care environment and considerable expertise is required for analysis of the trace It is usually not practical to undertake traditional EEG recordings at the time the baby shows abnormal movements More recently various technological developments have allowed more direct investigation of neuronal electrical activity by either video-EEG or compressed recording of the amplitude integrated EEG (aEEG or CFM)
Rennie et al3 at Kingrsquos College Hospital London have under-taken extensive evaluation of video-EEG and have found that this technique detects many convulsions not recognized by a single channel aEEG or CFM trace Of 19 infants with evidence of convulsions on EEG only four were recognized on CFM but this may have been due to the observersrsquo lack of experi-ence with this technique In other centres that have developed appropriate expertise aEEG or CFM has proved more sensitive to the detection of seizures Video-EEG studies have also shown that many movements interpreted by experienced clinicians to be seizures are not associated with abnormal cortical activity Conversely many electrical seizures are not associated with abnormal movements This is referred to as electroconvulsive dissociation
In summary clinical observation alone to detect the fitting baby is unreliable in that it may either over-detect seizure activ-ity which is not present on EEG or under-detect clinical seizures in infants with EEG-proven convulsions The decision as to which babies to treat with antiepileptic drugs therefore becomes somewhat arbitrary
Do anticonvulsants stop neonatal seizuresAlthough neonatal seizures are common there are few random-ized controlled trials assessing the benefits of antiepileptic drugs (AEDs) in the treatment of this condition Phenobarbitone is the most widely used first-line AED and in an Australasian study 95 of neonatologists and paediatric neurologists used this drug as first-line management12 The most commonly used loading dosage is 20 mgkg but regimens of up to 40 mgkg have been recommended (Table 3)13 Four trials have evaluated the effect of phenobarbitone in abolishing neonatal seizures Two of these studies used EEG to monitor response to the drug1415 and one compared phenobarbitone with phenytoin15 In the latter study seizures were completely controlled in only 43 of babies and in the group where phenytoin was the first drug used com-plete seizure control was achieved in 45 This study switched babies from their first AED to the other if complete control was not obtained on EEG monitoring after exposure to first-line therapy In babies who had been given phenobarbitone as first-line therapy seizure control was only achieved in 57 after phenytoin was added In those given phenytoin first complete
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Dosage regimens for first- second- and third-line anticonvulsants in the neonatal period
Loading dose Second loading dose if first
unsuccessfulMaintenance dose
phenobarbitone 20 mgkg by slow iv injection 10 mgkg iv 25ndash5 mgkg od
phenytoin 20 mgkg iv over 20 min not recommended
midazolam 150ndash200 μgkg iv infusion 1 μgkgmin iv infusion increasing to 5 μgkgmin
until favourable response
lidocaine 2 mgkg iv over 10 min 6 mgkgh for 6 h iv then 4 mgkgh for 12 h then
2 mgkgh for 12 h
lorazepam 005ndash01 mgkg by slow iv injection
Diazepam 03ndash04 mgkg iv over 3ndash5 min
lidocaine should not be used if the infant has previously been treated with phenytoin
Table 3
seizure control was achieved with the adding of phenobarbitone in 62
Boylan et al14 assessed the efficacy of phenobarbitone (20ndash40 mgkg iv over 20 min) in 14 babies monitored by video-EEG in only four was there complete abolition of seizures and in the other 10 electroconvulsive seizure activity increased whereas clinical evidence of seizures reduced This has been termed elec-troclinical dissociation and anticonvulsant drug use in the new-born appears to increase this feature They also showed that the babies least likely to respond to the first-line AED are those with the most abnormal background EEG
Two studies have evaluated the use of phenobarbitone in babies who had sustained significant asphyxial insult at birth Hall et al13 compared high-dose phenobarbitone (mean 39 mgkg) versus standard dose (27 mgkg) and reported fewer convul-sions and a significant reduction of severe disability or death in the high dose group (RR 030 CI 010ndash093) A recent study from India16 of babies with hypoxicndashischaemic encephalopathy ran-domized 25 babies to phenobarbitone (20 mgkg loading dose) and compared them with 20 control babies Only 2 of 25 (4) in the phenobarbitone group developed convulsions compared with 8 of 20 (40) in the control group (p = 001) Because of the specific enrolment criteria (asphyxial insult) neither of these studies is strictly comparable to the studies by Painter et al15 and Boylan et al14 whose intention was to assess the efficacy of first-line anticonvulsant therapy on convulsions of any cause diagnosed either clinically or by EEG
Other anticonvulsants used as second- and third-line drugs have been subject to few studies in the newborn Midazolam is administered as a bolus followed by continuous infusion A recent study17 has shown that in 10 of 13 neonates given intravenous midazolam for status epilepticus control of electri-cal seizures was achieved within the first hour of treatment having been previously shown to be refractory to phenobarbi-tone treatment Some of these babies required a second bolus infusion of midazolam to obtain control of all electrographic seizures
In some parts of Europe lidocaine is used as a third-line anti-convulsant Malingre et al18 evaluated 20 infants refractory to
paeDiatRiCS anD CHilD HealtH 184 180
both phenobarbitone and midazolam and who were then given lidocaine by continuous infusion Lidocaine was effective in abolishing electroconvulsive seizures diagnosed by aEEG in 76 of the treatment courses studied No babies developed cardiac arrhythmias a previously reported complication of lidocaine in older patients As a result of pharmacokinetic studies the dosage regimen has been modified (see Table 3)
In summary phenobarbitone is effective in seizure control in less than 50 of babies and even when combined with phe-nytoin the efficacy of these drugs together remains poor More worrying is the observation that phenobarbitone tends to reduce clinically evident seizures thereby giving the clinician a false sense of security whilst having little or no effect on the num-bers of electroconvulsive disorders This has been summarized appropriately as lsquoafter all these years we still love what doesnrsquot workrsquo19 Both midazolam and lidocaine infusions appear to be effective in abolishing severe seizures in some infants resistant to phenobarbitone Lidocaine should not be given to babies previ-ously exposed to phenytoin for fear of a synergistic adverse effect on cardiac rhythm
Do antiepileptic drugs cause brain damageA riskndashbenefit analysis is needed to evaluate the efficacy of anticonvulsants in stopping neonatal seizures which is poor with standard anticonvulsants as discussed above against the risk of administering the anticonvulsant drugs themselves Phenobarbitone has been reported to have adverse effects on the developing brain including inhibition of brain growth20 neuronal toxicity21 and adverse behavioural and cognitive effects into adult life when administered to young animals22 Phenytoin shows unpredictable plasma levels and potential cardiotoxicity
Recent studies have shown an effect of AED exposure on the developing brain by causing neurodegeneration23 Phenytoin administration to immature rat pups at doses which produce serum levels similar to those achieved in human neonates was associated with widespread neuronal death as a result of apop-tosis (programmed cell death) Phenobarbitone had a similar effect when a dosage regimen similar to 40 mgkg was used and
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
this effect was maximal in the more immature brain Diazepam and clonazepam also resulted in a similar effect Midazolam and lidocaine were not tested in this study The combination of phenobarbitone or phenytoin with diazepam had a particularly profound effect on neurodegeneration
In summary recent data suggest that the commonly used AEDs for neonatal convulsions may in themselves cause neuro-degeneration due to apoptosis with lasting effects on develop-ment Many babies with neonatal convulsions are treated with at least two AEDs and this may produce more severe adverse effects than the seizures themselves
Practical management of neonatal seizures
Assimilation of these data and formulation of a rational policy is difficult when faced with a fitting neonate on an intensive care unit and pressure on the medical staff to lsquodo somethingrsquo but it is important to accept that sometimes doing nothing is preferable to using potentially dangerous drugs in a situation which does not warrant such intervention Many babies who have normal interseizure neurological clinical findings and whose seizures are relatively brief and infrequent probably do not need anticon-vulsant medication A normal or near-normal background EEG trace should reassure the clinician that anticonvulsants can be withheld
Some causes of neonatal convulsions are treatable such as meningitis hypoglycaemia hypocalcaemia and inborn errors of metabolism and each baby should be rapidly and carefully investigated for cause of the convulsions
In some babies clinical assessment of seizures is difficult ie when the baby is very sick small or paralyzed Sometimes it may be difficult to assess the significance of certain movement pat-terns Under these circumstances an EEG may prove to be very helpful In many units EEG is not available out of hours and a simple aEEG or CFM is strongly advised Modern instruments are very simple to apply and prolonged or frequent seizures should be identified with only moderate training The printout can be faxed to a more senior doctor if there is doubt as to what is shown on the trace
The balance of knowledge now is that frequent seizures cause additional damage to the developing brain and that treatment to abolish the seizures is warranted Unfortunately there is little evidence that the majority of seizures can be effectively termi-nated by current standard therapy Furthermore it appears that the more abnormal the background EEG the more difficult it is to control the seizures Nevertheless a written protocol for the management of neonatal convulsions is required on each unit Phenobarbitone and phenytoin remain the mainstay of treat-ment although their effectiveness is disappointing There is little to suggest that midazolam is more effective than lidocaine as third-line therapy but lidocaine is precluded if phenytoin has been previously used
In view of the anxiety as to the neurodegenerative effects on the immature brain of most anticonvulsants used in the neonatal period (particularly when multiple drugs are used) it is prefer-able to use only one drug to maximum dosage before introduc-ing a second In addition the duration of anticonvulsants should be minimized and the drugs stopped at the earliest opportu-nity It is my practice to stop anticonvulsants prior to discharge
paeDiatRiCS anD CHilD HealtH 184 18
from hospital if the baby is neurologically normal on clinical examination
REFEREnCES
1 Ronen gm penney S andrews W the epidemiology of clinical
neonatal seizures in newfoundland a population-based study
J Pediatr 1999 134 71ndash75
2 lanska mJ lanska DJ Baumann RJ et al a population-based study
of neonatal seizures in Fayette County Kentucky Neurology 1995
45 724ndash732
3 Rennie Jm Chorley g Boylan gB et al non-expert use of the
cerebral function monitor for neonatal seizure detection Arch Dis
Child Fetal Neonatal Ed 2004 89 F37ndashF40
4 tekgul H gauvreau K Soul J et al the current etoliologic profile
and neurodevelopmental outcome of seizures in term newborn
infants Pediatrics 2006 117 1270ndash1280
5 Surtees R Wolf n treatable neonatal epilepsy Arch Dis Child 2007
92 659ndash661
6 Ben-ari y Holmes gl effects of seizures on developmental
processes in the immature brain Lancet Neurol 2006 5 1055ndash
1063
7 Holmes gl gairsa Jl Chevassus-au-louis n et al Consequences of
neonatal seizures in the rat morphological and behavioral effects
Ann Neurol 1998 44 845ndash857
8 Stafstrom Ce Chronopoulos a thurber S et al age-dependent
cognitive and behavioural deficits following kainic-acid inducing
seizures Epilepsia 1993 34 420ndash432
9 Schmid R tandon p Stafstrom Ce et al effects of neonatal seizures
on subsequent seizure-induced brain injury Neurology 1999 53
1754ndash1761
10 Hoffmann aF Zhao Q Holmes gl Cognitive impairment following
status epilepticus and recurrent seizures during early development
support for the ldquotwo-hit hypothesisrdquo Epilepsy Behav 2004 5
873ndash877
11 Wirrell eC armstrong ea osman lD et al prolonged seizures
exacerbate perinatal hypoxic-ischemic brain damage Pediatr Res
2001 50 445ndash454
12 Carmo KB Barr p Drug treatment of neonatal seizures by
neonatologists and paediatric neurologists J Paediatr Child Health
2005 41 313ndash316
13 Hall Rt Hall FK Daily DK High-dose phenobarbital therapy in term
newborn infants with severe perinatal asphyxia a randomized
prospective study with three-year follow-up J Pediatr 1998 132
345ndash348
14 Boylan gB Rennie Jm pressler Rm et al phenobarbitone neonatal
seizures and video-eeg Arch Dis Child Fetal Neonatal Ed 2002 86
F165ndash170
15 painter mJ Scher mS Stein aD et al phenobarbital compared with
phenytoin for the treatment of neonatal seizures N Engl J Med
1999 341 485ndash489
16 Singh D Kumar p narang a a randomized controlled trial of
phenobarbital in neonates with hypoxic ischemic encephalopathy
J Matern Fetal Neonatal Med 2005 18 391ndash395
17 Castro Conde JR Borges H Domenech martinez e et al midazolam
in neonatal seizures with no response to phenobarbital Neurology
2005 64 876ndash879
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
18 malingre mm Van Rooij lgm Rademaker Cma et al Development
of an optimal lidocaine infusion strategy for neonatal seizures Eur
J Pediatr 2006 165 598ndash604
19 Sankar R painter mJ neonatal seizures after all these years we still
love what doesnrsquot work Neurology 2005 64 776ndash777
20 Diaz J Schain J Bailey Bg phenobarbital-induced brain growth
retardation in artificially reared rat pups Biol Neonate 1977 32 77ndash82
21 mattson RH phenobarbital toxicity in levy RH Dreifuss Fe
mattson RH et al eds antiepipeptic Drugs 3rd edn new york
Raven 1985 p 341ndash355
22 mikati ma Holmes gl Chronopoulos a et al phenobarbital
modifies seizure-related brain injury in the developing brain Ann
Neurol 1994 36 425ndash453
23 Bittigau p Sifringer m genz K et al antiepileptic drugs and
apoptotic neurodegeneration in the developing brain Proc Natl
Acad Sci U S A 2002 99 15089ndash15094
paeDiatRiCS anD CHilD HealtH 184 182
Practice points
bull the clinician needs to be aware that almost any repetitive
stereotype movement pattern can be a manifestation of
neonatal seizures
bull eeg is important in defining neonatal seizures
bull Frequent short-lived seizures have been shown to cause long-
term neurodevelopmental problems
bull Conventional anticonvulsant medication is ineffective in
abolishing neonatal seizures in greater than 50 of cases
bull there is evidence that exposure of the neonatal brain to
multiple anticonvulsants causes neuronal death
bull Future research is needed to evaluate more effective
anticonvulsants for treating this condition
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
Emotional support for families of sick neonatesMarina nicolaou
cristine Glazebrook
AbstractParents of sick neonates experience high levels of stress anxiety and
depression Most interventions with families of sick infants have focused
on fostering the motherndashinfant relationship through the provision of
information about infant developmental needs or through increased
motherndashinfant contact Many of these studies have reported improved
maternal well-being though there are some concerns about the scope
and practicality of large-scale interventions The few studies to have
prioritized emotional support for parents of sick neonates have pro-
duced encouraging results even interventions requiring relatively few re-
sources such as telephone support parent-to-parent support and group
support have been associated with reduced psychological morbidity for
parents The needs of parents can change throughout their infantrsquos hos-
pitalization and not all want or benefit from the provision of additional
support Thus neonatal intensive care units should aim to provide a
varied flexible and sustainable programme of support options Further
research should focus on the needs of fathers
Keywords mental health neonatal intensive care parents
The admission of an infant to neonatal care is acknowledged to be a source of considerable distress for families This review aims to explore evidence for the psychological impact on families of having an infant in neonatal intensive care and to identify evi-dence for the effectiveness of interventions to promote parental well-being It will conclude with recommendations for strategies to support parents of vulnerable infants and suggestions for fur-ther research
Psychological impact of neonatal care for parents
The majority of research examining the effect on parents of having a sick neonate has focused on families of premature or low birthweight infants Such research has found that parents with a sick neonate exhibit high levels of stress compared to normative samples and to parents of healthy full-term infants1 Singer et al2 examined the stress experienced by mothers of high-risk very low birthweight (VLBW) low-risk VLBW and term
Marina Nicolaou MPhil is a Teaching Assistant at the School of
Community Health Sciences University of Nottingham Nottingham UK
Cristine Glazebrook PhD is a Professor of Health Psychology at the School
of Community Health Sciences University of Nottingham Nottingham UK
PaeDiaTrics anD cHilD HealTH 184 196
infants Several self-report measures were used including the Brief Symptom Inventory the Parenting Stress Index (PSI) the Impact on Family Scale and the Family Inventory of Life Events and Changes (FILE) Mothers of VLBW infants had more psycho-logical distress at 1 month compared to mothers of term infants Mothers of high-risk VLBW infants also reported high psycho-logical distress at 2 years and high levels of parenting stress at 3 years Mothers have also been found to have higher stress levels compared to fathers Shaw et al3 examined the prevalence of acute stress disorder (ASD) in 40 parents whose infants were in the neonatal intensive care unit (NICU) Nearly half of the moth-ers (44) met the criteria for ASD although none of the fathers did Furthermore the severity of the symptoms (measured by the number of concurrent symptoms) was greater for the moth-ers than for the fathers3 The reasons behind this difference have been widely speculated with some believing that it is due to the mothersrsquo greater psychological involvement with the infant as evidenced by their general greater vulnerability to postpartum psychological disorder It could also reflect gender differences in coping style
Having an infant who requires intensive medical care repre-sents a significant emotional burden for families Not only is there extreme anxiety surrounding the infantrsquos health and distress for the childrsquos suffering there is also the unfamiliar and intimidating environment of the NICU to adjust to Hopper in her review of the literature identified sources of stress for parents of sick neo-nates as falling into three areas4 Situational factors included the severity of the infantrsquos illness and how parents adapted to the life crisis of having a sick infant Personal factors involved parental emotions about their roles and the instrumental and informa-tional support which were available to them The third area was classified as environmental sources of stress and included the environment of the NICU and the relationship between parents and members of staff This relationship has been examined by several studies in the nursing literature nurses are seen as ide-ally placed to provide the necessary support and information to parents with sick neonates However whilst some studies have shown that supportive and helpful hospital staff can have a posi-tive effect on parents other studies have highlighted the prob-lems and difficulties which can manifest It has been shown that parents and nurses often have very different ideas about issues eg the necessary skills and competencies needed in an NICU or the characteristics that make a lsquogood motherrsquo
Research has shown that there may be a relationship between high levels of parental stress and an increased likelihood of depression5 Postpartum depression is a psychiatric illness which appears in 10ndash15 of postpartum women Its reported preva-lence rates however have ranged from less than 10 up to 306 depending on the instruments used the population exam-ined and the timing of the research Several factors have been found to be associated with postpartum depression including poor social support and infant-related stressors6 Evidence indi-cates that postnatal depression may be underreported and this is of concern since the mental and psychological health of the mother can affect her relationship with her infant and thus the infantrsquos cognitive and emotional development5 Depressed moth-ers appear to look touch and talk to their infants less frequently and also appear to show fewer positive and more negative faces7 The vocalizations of mothers suffering with depression have also
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
been found to be less effective at promoting cognitive growth and learning in infants8
If researchers are interested in finding ways of providing sup-port for families of sick neonates then they must listen to what such families perceive their needs to be in order to avoid increas-ing anxiety and distress Furthermore the provision of appropri-ate support be it emotional informational or social will enhance parental coping abilities increase self-esteem and reduce anxiety It should be noted though that the research conducted around these issues has often taken lsquosupport needsrsquo as being synony-mous with lsquoinformation needsrsquo Such studies have examined the type the amount and quality of information that parents receive and perceive themselves as needing but have not explored in equal depth the perceived emotional support needs of families who have a sick infant In addition the needs of parents may change throughout their infantrsquos illness Ward examined the per-ceived needs of 52 parents of infants in an NICU9 Parents rated the needs of their hospitalized infant as most important along with the need to be reassured Interestingly they ranked their support needs as least important This research was conducted during the first week of the infantsrsquo hospitalization however which would explain the preoccupation of the parents with the infantrsquos health These results demonstrate that if researchers want to find ways of providing emotional support to parents of sick neonates they must be prepared not only to listen to parents but also to be flexible enough to satisfy the parentsrsquo changing needs and expectations
Interventions aimed at supporting parents
Most interventions that been evaluated in controlled studies have focused on supporting the motherndashinfant relationship and provid-ing information on infant development Many of these interven-tions have included the aim of improving the parental emotional state and thus psychological outcomes such as stress or anxi-ety have been assessed However few studies appear to include fathers This means that strategies implemented to provide emo-tional support to families of sick neonates are often derived from interventions tailored for mothers even though fathers may have different emotional needs
A wide range of interventions with mothers and infants has been evaluated in the NICU Increasing motherndashinfant contact through kangaroo care has been found to reduce maternal anxiety1011 and educational programmes delivered to fami-lies in the NICU have also been associated with reduced emo-tional difficulties in parents12ndash14 Kaaresen and colleagues implemented an intervention which consisted of eight sessions before discharge and four home visits all by trained nurses The sample included 71 premature infants in the intervention group 69 premature infants in the control group and 74 infants in the full-term control group The randomized controlled trial found that the intervention reduced parenting stress in both mothers and fathers of premature infants compared to controls to a level equivalent to parents in the term control group13 At 6 months corrected age mothers of preterm infants who had not received the intervention had total PSI scores which were 17 points higher than the mothers of infants born at term (an effect size of 057) A similar study evaluated the efficacy of an educationalndashbehavioural programmendashCreating Opportunities for
PaeDiaTrics anD cHilD HealTH 184 19
Parent Empowerment (COPE) ndash through a randomized controlled trial with 260 families of premature infants14 COPE was a four-phase educationalndashbehavioural programme which began as early as 2ndash4 d after mothers had given birth and continued until 1 week after discharge from the NICU The programme consisted of audiotaped and written infant behaviour information along with photographs which focused on common behaviours and characteristics of premature infants It also included various par-ent activities in the form of a four-phase workbook which aimed to assist mothers in the implementation of the experimental infor-mation COPE was found significantly to reduce maternal stress in the NICU as well as maternal anxiety and depressive symptoms after hospitalization In contrast a cluster randomized trial of a parenting intervention delivered to mothers of very premature infants from soon after birth showed no benefits for parenting stress1 The authors hypothesized that the intervention had not been of sufficient intensity particularly in the weeks surrounding discharge Neonatal care presents a significant barrier to parent-ing in the early weeks following a very preterm birth and so inter-ventions which focus on the developmental needs of infants and the parentndashchild relationship should particularly aim to support parents as they take on the parenting role There was also concern that the intervention had failed to reach those most at risk
Since large-scale projects can be costly to implement and may often fail to reach the families in most need it may be wiser to focus on intervention programmes which are more practical and easier to implement within a neonatal care setting Research has shown that even interventions which are based on one-off meet-ings with parents of sick neonates can be effective Jotzo and Poets examined the effect of an intervention programme aimed at reducing the severity of traumatic responses as a result of giv-ing birth prematurely15 Their programme consisted of a one-off intervention meeting along with additional psychological help throughout the hospitalization of the infant The meeting cov-ered a variety of issues including a reconstruction of the events shortly before and after the infantrsquos birth relaxation techniques discussion of coping strategies available resources and social support and support during emotional outbursts The measures used included the Impact of Event Scale (IES) and the Peritrau-matic Dissociative Experience Questionnaire At discharge the mothers who received the intervention were found to have a significantly lower traumatic impact as a result of premature birth Furthermore fewer mothers in the intervention group showed symptoms of clinically significant psychological trauma at discharge compared to mothers in the control group (36 vs 76)15 The lsquoParents Circle Programrsquo is another intervention with a similar structure16 This consisted of a 90 min session for parents with the aim of enhancing the developing relationship between parents and infants and to offer parents support A total of 104 parents (59 mothers and 45 fathers) and 44 members of hospital staff were asked to evaluate the programme and their results were analysed using content analysis Families reported gaining perspective on their situation feeling supported becom-ing aware of cues and optimizing interactions and becoming aware of available resources Parents and staff alike felt that participating in the intervention helped parents overcome the difficulties associated with the early time of their infantrsquos hos-pitalization Additional studies have also found positive results with fairly minimal interventions including discussion groups
7 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
in the NICU music during kangaroo care and pairing mothers of sick neonates with trained mothers who had been through similar experiences
Parent support programmes
Parent support programmes (PSPs) which are based in NICUs can provide parents with the opportunity to talk to parents who have been in similar situations and also to discuss their emo-tions with professionals who can help them cope with their situa-tion111718 The parent-to-parent support programme for mothers of preterm infants evaluated by Preyde and Ardal included edu-cational parental support group meetings and individual par-ent-to-parent support (primarily telephone support)19 Measures used included the Parental Stressor Scale NICU the State and the Trait Anxiety Inventories and the Beck Depression Inven-tory After 4 months of participation mothers in the intervention group reported lower levels of stress state anxiety and depres-sion compared to control group mothers The authors speculated however that the participants who were able to meet face to face with other parents were those who benefited the most Hurst conducted a comprehensive survey of an NICU-based PSP This PSP was provided in a variety of formats including a weekly parent support group hospital visitation and 24-h telephone sup-port20 Of the 477 participants 303 families used the PSP dur-ing a 2-year evaluation period with 78 using only one form of support and 18 using two forms Of a sub-sample of 48 parents asked to complete an evaluation of the PSP 92 stated that they would recommend such a programme to other parents Furthermore the majority of parents felt that it made them feel supported and helped them deal with their emotions20 This is an indication that such programmes can be very successful in sup-porting parents throughout their infantrsquos hospitalization It also shows that it can be beneficial to give parents several options and formats when it comes to such support services It is impor-tant to consider though that both the Hurst and the Preyde and Ardal studies found that some participants did not find the sup-port programmes helpful even reporting that they had caused them increased stress and anxiety Therefore it should not be assumed that support programmes will suit every individual and will provide the required support for all parents1920 NICUs need to be flexible enough to provide parents with a range of forms of support to choose from
The increased understanding of the strains that parents of sick neonates have to deal with has also led to efforts to improve customary practices in NICUs Family-centred care focuses on infants and their needs and attempts to redefine the relationship between parents and caregivers These practices strive to provide parents with support during their infantrsquos illness by focusing on freely sharing information and on the collaboration between parents and hospital staff Family-centred care has been found to be associated with several beneficial outcomes including improved parental satisfaction increased parental comfort staff satisfaction and decreased parental stress18 Research is already examining these practices and questioning how these can be improved further Such research reflects the increasing effort focused on lsquohumanizingrsquo the environment in NICUs in order to make parents feel more comfortable about spending time with their infants
PaeDiaTrics anD cHilD HealTH 184 19
Conclusion
Surprisingly few interventions have prioritized the provision of emotional support for parents of sick neonates or accounted for the changing needs and wishes of parents over the course of their infantrsquos care Large-scale supportive education-based inter-ventions have been shown to be effective in reducing parental distress However the feasibility and sustainability of such pro-grammes should also be considered Programmes which require significant additional resources can be expensive and there are also issues of training and quality control Interventions which require significant input from parents may also place additional burdens on families making them potentially less accessible to those most at risk Arguably the aim should be to explore ways of providing acceptable and effective informational support which could be complemented by emotional support from health professionals and from other parents in the unit Increasingly studies are exploring the use of computers and multimedia as an engaging flexible and cost-effective method of targeting indi-vidual needs and providing support and information Such com-puter-based and interactive multimedia interventions have been found to be successful with a range of patient groups and could therefore be examined as a complementary method of providing informational support to families with sick neonates
REfEREnCEs
1 Glazebrook c Marlow n israel c et al randomised trial of a
parenting intervention during neonatal intensive care Arch Dis Child
Fetal Neonatal Ed 2007 92 F438ndash443
2 singer lT salvator a Guo s collin M lilien l Baley J Maternal
psychological distress and parenting stress after the birth of a very
low-birth-weight infant JAMA 1999 281 799ndash805
3 shaw rJ Deblois T ikuta l Ginzburg K Fleisher B Koopman c
acute stress disorder among parents of infants in the neonatal
intensive care nursery Psychosomatics 2006 47 206ndash212
4 Hopper a sources of stress for parents of a sick neonate a
literature review Pediatr Nurs 2000 30 29ndash32
5 Davis l edwards H Mohay H wollin J The impact of very
premature birth on the psychological health of mothers Early Hum
Dev 2003 73 61ndash70
6 Bernazzani O saucier J-F David H Borgeat F Psychosocial
predictors of depressive symptomatology level in postpartum
women J Affect Disord 1997 46 39ndash49
7 Field T infants of depressed mothers Infant Behav Dev 1995 18
1ndash13
8 Kaplan Ps Bachorowski J-a Zarlengo-strouse P child-directed
speech produced by mothers with symptoms of depression fails
to promote associative learning in 4-month-old infants Child Dev
1999 70 560ndash570
9 ward K Perceived needs of parents of critically ill infants in
a neonatal intensive care unit (nicU) Pediatr Nurs 2001 27
281ndash286
10 lai Hl chen cJ Peng Tc et al randomized controlled trial of music
during kangaroo care on maternal state anxiety and preterm infantsrsquo
responses Int J Nurs Stud 2006 43 139ndash146
8 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
11 Tallandini Ma scalembra c Kangaroo mother care and mother-
premature infant dyadic interaction Infant Ment Health J 2006 27
251ndash275
12 Ohgi s Fukuda M akiyama T Gima H effect of an early intervention
programme on low birthweight infants with cerebral injuries
J Paediatr Child Health 2004 40 689ndash695
13 Kaaresen Pi ronning Ja Ulvund se Dahl lB a randomized
controlled trial of the effectiveness of an early-intervention program
in reducing parenting stress after preterm birth Pediatrics 2006
118 e9ndash19
14 Melnyk BM Feinstein nF alpert-Gillis l et al reducing premature
infantsrsquo length of stay and improving parentsrsquo mental health
outcomes with the creating opportunities for parent empowerment
(cOPe) neonatal intensive care unit program a randomized
controlled trial Pediatrics 2006 118 e1414ndash1427
15 Jotzo M Poets cF Helping parents cope with the trauma of
premature birth an evaluation of a trauma-preventive psychological
intervention Pediatrics 2005 115 915ndash919
16 Pearson J andersen K evaluation of a program to promote positive
parenting in the neonatal intensive care unit Neonatal Netw 2001
20 43ndash48
17 roman l lindsay J Boger r et al Parent-to-parent support
initiated in the neonatal intensive care unit Res Nurs Health 1995
18 385ndash394
18 Meyer ec coll cTG lester BM Boukydis cFZ McDonough sM Oh w
Family-based intervention improves maternal psychological well-
being and feeding interaction of preterm infants Pediatrics 1994
93 241ndash246
PaeDiaTrics anD cHilD HealTH 184 19
19 Preyde M ardal F effectiveness of a parent ldquobuddyrdquo program for
mothers of very preterm infants in a neonatal intensive care unit
CMAJ 2003 168 969ndash973
20 Hurst i One size does not fit all Parentsrsquo evaluations of a support
program in a newborn intensive care nursery J Perinat Neonatal
Nurs 2006 20 252ndash261
Practice points
bull Parents of sick neonates experience significant distress and
exhibit higher levels of stress anxiety and depression than
parents of healthy infants
bull educational support emotional support and increased
motherndashinfant contact have been shown to promote maternal
well-being
bull emotional support for fathers has been largely neglected in
the research literature
bull Parents benefit from a choice of supportive facilities which
could include face-to-face sessions with health professionals
telephone support hospital visitation parent-to-parent
support and unit-based group support meetings
bull Parentsrsquo support needs can change during their infantrsquos
hospitalization and not all parents want or benefit from the
provision of additional information and emotional support in
the neonatal unit
9 copy 2008 elsevier ltd all rights reserved
Personal Practice
When should enteral feeds be started in preterm infantsnicholas D embleton
AbstractPaediatricians are regularly faced with the question of when best to start
enteral feeds in preterm infants this is important as longer term out-
come may be compromised by sub-optimal nutrition in early life clinical
factors that may affect the decision to start and the risk and benefits
are discussed
Keywords breast milk feeding nutrition parenteral nutrition
Key points in the history
Alice is lsquonutritionally vulnerablersquo and whilst this may not be immediately apparent it will affect her long term outcome Her energy stores are extremely limited and consist primarily of pro-tein She has less than 5 fat and little energy associated with stored glycogen She is losing about 1 gkgd protein equivalent so she needs at least that and a minimum of 50ndash60 kcalkg of energy just to maintain the status quo let alone grow
Her weight is on the 25th centile Review of any antenatal his-tory may reveal whether fetal growth was normal Fetal growth retardation can occur with a weight greater than 10th centile The presence of antenatal absent or reversed end diastolic flow in the umbilical artery indicates poor gut blood flow This increases the risk of necrotizing enterocolitis (NEC) and might suggest a more cautious approach to starting feeds1
She has no important cardiovascular problems but if she were hypotensive gut blood flow may be low There is no umbilical
Nicholas D Embleton BSC (Hons) MBBS (Hons) MD FRCPCH is Consultant in
Neonatal Medicine at Newcastle Neonatal Service Royal Victoria
Infirmary Newcastle upon Tyne NE1 4LP UK
Should you start feeds at a day of age
alice was born following spontaneous labour at 30 weeksrsquo
gestation she weighed 1300 g and is now 18 h old she was
briefly ventilated and then extubated to continuous positive
airway pressure 12 h ago in 35 oxygen she has had caffeine
citrate but still has intermittent episodes of self-correcting
apnoea she was commenced on iv 10 dextrose but this was
replaced by a parenteral amino acid solution (referred to as
lsquotPnrsquo) along with intralipid at 0900 this morning serum glucose
is 11 mmoll and blood pressure is 42 systolic
PaeDiatrics anD cHilD HealtH 184 20
arterial catheter in situ but there is no good evidence that this should delay the decision to start feeds Her glucose is high but this is quite common in a baby like this Could this be a sign of sepsis Caffeine does not affect the incidence of NEC2 The great-est risk factor for NEC in this case is prematurity
What else might be found on examination
Up until 24 h ago she was swallowing large amounts of amniotic fluid What will have changed since then
General examination should confirm peripheral perfusion lsquogestaltrsquo view (does she look lsquowellrsquo) and cardiovascular status lsquoBowel soundsrsquo are not usually helpful
The most important variable likely to affect gut perfusion is the arterial duct Precordial lsquoheaversquo and a loud murmur are sug-gestive but it is possible to have a significant ductal shunt in a baby with a normal examination Cardiac ultrasound will con-firm this diagnosis It might be better to treat a large shunt first with indometacin and to delay starting feeds for a further 24 h
It is not possible to assess gut perfusion clinically but normal perfusion elsewhere (adequate urine output usually indicates adequate renal perfusion) would be reassuring Most preterm babies have a few abdominal lsquoloopsrsquo visible but a distended abdomen with many palpable loops suggests ileus This might be secondary to sepsis or poor gut blood flow Preterm babies do not pass much meconium in the first 24ndash48 h
Balance of risks between starting and withholding feeds
Alice requires 35ndash4 gkgd of protein and 120 kcalkgd to grow3 This will initially be provided parenterally Delaying feeds increases the risk of gut villous atrophy and prolongs the need for lsquototal parenteral nutrition (TPN)rsquo TPN requires intravenous access and so increases the risk of sepsis and when prolonged use is required combined with the lack of enteral feeding may result in hepatic impairment
Delaying feeds may allow a gut that has been chronically under-perfused to re-establish more normal perfusion although normal gut endocrine function digestive enzyme upregulation and motility require a source of intraluminal nutrients1 A recent study suggested benefit from delaying the introduction of feeds4 but methodologi-cal problems exist5 Although a Cochrane meta-analysis suggested no benefit only two studies were included6 A large UK-based trial is examining the effect of early or late feeding in preterm infants who were born growth retarded following identification of antena-tal absent or reversed end diastolic flow in the umbilical artery7
When starting feeds what volume should be used
There are no good data to guide this decision We start with 24 mlkg (1 mlkgh) and then increase by this amount each day Most babies achieve full enteral feeds (ge150 mlkgd) by a week of age Feeding guidelines improve the outcome8 Measure-ment or assessment of gastric aspirates is not consistently useful in predicting subsequent feeding intolerance or development of NEC Aspirate volumes equivalent to or sometimes greater than the amount given in the preceding 1ndash2 h are usually normal Most aspirates have a greenish colour Thick bloody or intensely bile-stained aspirates require detailed assessment
0 copy 2008 elsevier ltd all rights reserved
Personal Practice
What else affects decisions and outcome
Feeding success is affected by sepsis and NEC Scrupulous atten-tion should be paid to hand washing and intravenous access and blood sampling should be minimized There is no good evidence to support the routine use of pro-kinetic agents or H2 blockers
The most important clinical intervention affecting the occur-rence of NEC is the use of breast milk9 All efforts should be directed at persuading parents of the benefits and supporting the process Some clinicians delay starting feeds for a further 24 h whilst expressed breast milk becomes available Donor breast milk might be equally efficacious10
RefeRenceS
1 Dorling J Kempley s leaf a Feeding growth restricted preterm
infants with abnormal antenatal Doppler results Arch Dis Child Fetal
Neonatal Ed 2005 90 F359ndash363
2 schmidt B roberts rs Davis P et al caffeine therapy for apnea of
prematurity N Engl J Med 2006 354 2112ndash2121
PaeDiatrics anD cHilD HealtH 184 20
3 embleton nD Pang n cooke rJ Postnatal malnutrition and growth
retardation an inevitable consequence of current recommendations
in preterm infants Pediatrics 2001 107 270ndash273
4 Berseth cl Bisquera Ja Paje VU Prolonging small feeding volumes
early in life decreases the incidence of necrotizing enterocolitis in
very low birth weight infants Pediatrics 2003 111 529ndash534
5 Menon G Boyle eM embleton nD et al introduction of enteral
feeds in preterm infants Pediatrics 2004 114 327ndash328
6 Kennedy Ka tyson Je chamnanvanikij s early versus delayed
initiation of progressive enteral feedings for parenterally fed low
birth weight or preterm infants Cochrane Database Syst Rev 2000
cD001970
7 wwwnpeuoxacukadept
8 Patole sK de Klerk n impact of standardised feeding regimens on
incidence of neonatal necrotising enterocolitis a systematic review
and meta-analysis of observational studies Arch Dis Child Fetal
Neonatal Ed 2005 90 F147ndash151
9 lucas a cole tJ Breast milk and neonatal necrotising enterocolitis
Lancet 1990 336 1519ndash1523
10 Boyd ca Quigley Ma Brocklehurst P Donor breast milk versus
infant formula for preterm infants systematic review and meta-
analysis Arch Dis Child Fetal Neonatal Ed 2007 92 F169ndash175
1 copy 2008 elsevier ltd all rights reserved
self-assessment
Case 1A term male infant born to consanguineous parents is assessed at 24 h of age due to poor feeding profuse yellow watery diar-rhoea and irritability He weighed 32 kg at birth and delivery was uneventful There was no polyhydramnios He has been breastfed since birth On examination he is pale with a non-tender but distended abdomen and reduced bowel sounds His weight is 275 kg and he looks dehydrated Examination is otherwise normal
Initial investigations (normal values in parentheses) showed
sodium 149 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 65 mmollitre (25ndash75)
creatinine 147 μmollitre (40ndash110)
chloride 119 mmollitre (95ndash105)
haemoglobin 172 gdl (140ndash200)
White blood cell count 80 times 109litre (100ndash260)
Platelet count 302 times 109litre (150ndash400)
arterial blood gas
ph 720 (730ndash745)
PcO2 23 kPa (46ndash60)
Bicarbonate 68 mmollitre (220ndash260)
Base excess minus186 mmollitre (minus20 to +20)
lactate 59 mmollitre (06ndash24)
An abdominal X-ray shows distended bowel loops with no intramural thickening or pneumoperitoneum (Figure 1)
He was given nil by mouth and received intravenous fluids and antibiotics His dehydration improved but the metabolic acidosis and diarrhoea persisted despite receiving no enteral feeds and the commencement of total parenteral nutrition Blood and stool cultures were negative
1 Which of the following best describes these results Choose ONE answer ONLY from the followingA Hypernatraemia hyperchloraemic metabolic acidosis
with increased anion gapB Hypernatraemia hyperchloraemic metabolic acidosis
with normal anion gap
Manish Sadarangani BM BCh MA MRCPCH is Clinical Research Fellow
at the Department of Paediatrics University of Oxford Centre for
Clinical Vaccinology and Tropical Medicine Churchill Hospital
Oxford OX3 7LJ UK
Shabna Rajapaksa MB BChir MA MRCPCH is Specialist Registrar in
Paediatrics at the Paediatric Intensive Care Unit John Radcliffe
Hospital Oxford OX3 9DU UK
Nicholas Mann MD FRCP FRCPCH DCH is Consultant Paediatrician at the
Department of Paediatrics Royal Berkshire Hospital Reading RG1
5AN UK
self-assessment
C Hypernatraemic dehydration and compensated metabolic acidosis
D Acute renal failureE Renal tubular acidosis
2 What is the likely diagnosis Choose ONE answer ONLY from the followingA Hirschsprung disease ndash long segmentB Cystic fibrosis with meconium ileusC Microvillus inclusion diseaseD Cowrsquos milk protein intoleranceE Lactose intolerance
3 What is the investigation of choice Choose ONE answer ONLY from the followingA Rectal biopsy with staining for acetylcholine receptorsB Immunoreactive trypsinC Gastrointestinal endoscopy and biopsyD Stool microscopy and cultureE Stool reducing substances
Case 2A 4-year-old boy presents with a 3 d history of jaundice and a florid rash He has had orange urine and there is no change in his stool colour His family originate from Kosovo and have lived in the UK for the last 8 years He has never left the UK There is no history of blood transfusion or sex-ual abuse The grandmother was recently diagnosed with hepatitis B
On examination he is well apyrexial and mildly jaundiced with cervical and axillary lymphadenopathy He has an exten-sive papular rash over the face extremities and trunk (Figure 2) There is 3 cm hepatomegaly with no splenomegaly or ascites Examination is otherwise normal
Figure 1 abdominal X-ray of baby
Paediatrics and child health 184 202 copy 2008 elsevier ltd all rights reserved
self-assessment
Initial investigations are as follows
haemoglobin 110 gdl (113ndash135)
White blood cell count 108 times 109litre (50ndash150)
Platelet count 278 times 109litre (150ndash400)
inr 10 (08ndash12)
aPt ratio 10 (08ndash13)
sodium 140 mmollitre (135ndash145)
Potassium 42 mmollitre (35ndash50)
Urea 56 mmollitre (25ndash75)
creatinine 65 μmollitre (45ndash120)
total bilirubin 66 μmollitre (0ndash15)
conjugated bilirubin 23 μmollitre (0ndash10)
alanine aminotransferase (alt) 2033 iUlitre (0ndash35)
alkaline phosphatase 987 iUlitre (71ndash234)
Gamma-glutamyl transferase (GGt) 870 iUlitre (0ndash51)
1 What is the name of this rash Choose ONE answer ONLY from the followingA Erythema multiformeB Erythema migransC GianottiminusCrosti syndromeD EczemaE Dermatitis herpetiformis
2 What is the most likely diagnosis Choose ONE Answer ONLY from the followingA Autoimmune hepatitisB Hepatitis BC Hepatitis DD Wilson diseaseE Alpha-1 antitrypsin deficiency
3 What is the best means of management Choose ONE answer ONLY from the followingA Isolation until the jaundice disappearsB ImmunosuppressionC Copper chelating agents and genetic counsellingD Patient and family education with consideration of
antiviral agentsE Liver transplantation
Case 3A 10-month-old boy presents with 3 weeks of vomiting and constipation ndash he is passing hard stools every 2ndash3 days He has fallen from the 9th to below the 04th centile in the last 6 weeks He passed meconium within the first 24 h of life On examina-tion he looks pale and there are some dysmorphic features ndash a short nose long philtrum and wide mouth He has normal heart sounds with a grade 3 ejection systolic murmur loudest at the upper right sternal edge Examination is otherwise normal
Initial investigations are as follows
haemoglobin 91 gdl (113ndash141)
total white blood cell count 124 times 109litre (60ndash170)
Platelet count 407 times 109litre (150ndash400)
sodium 144 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 78 mmollitre (25ndash75)
creatinine 78 μmollitre (45ndash120)
albumin 52 glitre (35ndash50)
corrected calcium 384 mmollitre (238ndash263)
Phosphate 167 mmollitre (099ndash157)
1 What is the most likely diagnosis Choose ONE answer ONLY from the followingA HyperparathyroidismB Acute leukaemiaC Williams syndromeD Hypervitaminosis DE Familial hypocalciuric hypercalcaemia
2 Which investigation would be most useful in establishing the diagnosis Choose ONE answer ONLY from the followingA Intact parathyroid hormone assayB Blood filmC Fluorescent in-situ hybridization for 7q1123 deletionD 25-hydroxyvitamin D assayE Urine calciumcreatinine ratio
3 Which of the following treatments would not be suitable for this patient Choose ONE answer ONLY from the followingA Low calcium dietB Normal saline infusionC FurosemideD CorticosteroidsE Bisphosphonates
Case 4A 10-week-old girl presents with a 2-day history of poor feed-ing Her mother has been concerned about weakness since birth She only has a flicker of movement in the arms none in the legs and has a weak cry She has been passing urine and opening her bowels normally She was born at full term by normal delivery and did not require any resuscitation at birth Normal fetal movements were felt antenatally and there was no polyhydramnios She is the first child of non- consanguineous parents and there is no significant family his-tory On examination she is alert and fixing and following appropriately She has a weak cry and a weak suck There is reduced central and peripheral tone with marked head lag
Figure 2 rash found on examination
Paediatrics and child health 184 203 copy 2008 elsevier ltd all rights reserved
self-assessment
Muscle power is grade 3 out of 5 in the arms and legs There is no muscle or tongue fasciculation and she has absent reflexes throughout The remainder of the examination is normal
Electromyogram shows irregular polyphasic motor unit potentials with marked instability consistent with a dener-vating and re-innervating process (Figure 3)
1 Which of the following additional investigations may be helpful Choose ONE answer ONLY from the followingA Nerve conduction studiesB Creatine kinase assayC Muscle biopsyD SMN1 gene analysisE All of the above
2 What is the most likely cause of this childrsquos symptoms Choose ONE answer ONLY from the followingA Congenital myotonic dystrophyB Duchenne muscular dystrophyC PraderminusWilli syndromeD Spinal muscular atrophyE Mitochondrial myopathy
3 What is the mode of inheritance of this disease Choose ONE answer ONLY from the followingA X-linked recessiveB Autosomal recessiveC Autosomal dominantD MitochondrialE Sporadic
Case 5A 13-year-old girl presents with a 3-week history of fever up to 40degC night sweats and headache She has a reduced appetite with some weight loss She has no other specific symptoms She was on holiday in China 7 months ago On examination she looks well and has a temperature of 387degC There is no lymphadenopathy and no rashes Examination is entirely normal
Results of investigations are as follows
haemoglobin 126 gdl (120ndash160)
total white blood cell count 132 times 109litre (43ndash108)
neutrophil count 115 times 109litre (25ndash75)
Platelet count 244 times 109litre (150ndash400)
Blood film neutrophilia with left shift
erythrocyte sedimentation rate 63 mmh (1ndash20)
c-reactive protein 219 mglitre (0ndash5)
Blood culture Streptococcus intermedius
from anaerobic bottle only
csf culture negative
Magnetic resonance imaging (MRI) of the brain shows acute frontal sinusitis with a large intracranial frontal extra-dural empyema (Figure 4)
1 Which of the following would be appropriate management Choose ONE answer ONLY from the followingA A 12-week course of intravenous antibioticsB Drainage of the frontal sinus followed by 2 weeks of
intravenous antibioticsC Drainage of the empyema followed by 2 weeks of
intravenous antibioticsD Drainage of the empyema and the frontal sinus
followed by 2 weeks of oral antibiotics
1151
1152
1153
1154
1155
1156
1157
1158
1159
1200
50ms 1mV
Figure 3 electromyogram recording from the patient Figure 4 Parasagittal section from mri scan of patient
Paediatrics and child health 184 204 copy 2008 elsevier ltd all rights reserved
self-assessment
E Drainage of the empyema and the frontal sinus followed by 8 weeks of intravenous antibiotics
2 Streptococcus intermedius is a potential pathogen in which of the following infections Choose ONE answer ONLY from the followingA Liver abscessB Urinary tract infectionC MeningitisD Thoracic empyemaE Pneumonia
3 Which of the following statements regarding lsquopyrexia of unknown originrsquo in children is false Choose ONE answer ONLY from the followingA Malignancy is the underlying pathology in 5ndash15 of
casesB An aetiology will be found in over 90 of casesC The most common cause is infectionD A rheumatological cause is found in 10ndash20 of casesE Familial Mediterranean fever can occur in children of
non-Mediterranean ethnicity
Answers
Case 11 AThe anion gap is a useful tool to differentiate the causes of a metabolic acidosis It is calculated by the equation
Anion gap = [Na K ] [Cl HCO ]3+ + minus minus+ minus +
It represents the effect of unmeasured anions on the plasma pH and is normally 10ndash18 mmollitre
2 CMicrovillus inclusion disease is a severe autosomal recessive enteropathy that is typically apparent within hours or days after birth It is the second most common cause of protracted diarrhoea in the newborn after infectious causes It is characterized by severe yellow watery diarrhoea and malabsorption due to hypoplasia andor atrophy of the villi of the small intestine secondary to an inherited defect in the brush border membrane This results in severe dehydration malnutrition and metabolic acidosis due to bicarbonate loss from the gut
3 CDiagnosis of microvillus inclusion disease is made on small bowel biopsy Electron microscopy findings are of intracellular brush border inclusions and densely packed apical cytoplasmic vesicular bodies indicating microvillous atrophy There is no cure Treatment is supportive with total parenteral nutrition and consideration of small bowel transplantation
Further reAding
Goulet O ruemmele f causes and management of intestinal failure
in children Gastroenterology 2006 130(suppl 1) s16ndash28
rhoads Jm Vogler rc lacey sr et al microvillus inclusion disease
In vitro jejunal electrolyte transport Gastroenterology 1991
100 811ndash817
Case 21 CGianottindashCrosti syndrome is a distinct self-limiting rash commonly associated with viral infections in children between 2 and 6 years of age It presents as multiple pink to redminusbrown papules or papulovesicles which may be pruritic and can become confluent Gianotti and Crosti initially described the exanthema as associated with hepatitis B virus and they termed it papular acrodermatitis of childhood It can occur in several viral diseases eg hepatitis A B and C coxsackie viruses and cytomegalovirus
2 BHepatitis is a syndrome characterized by inflammation or injury of liver cells which may develop into cell necrosis and subsequently fibrosis andor cirrhosis Biochemically there are raised liver enzymes The degree of transaminase elevation does not correlate with the severity of the disease process Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of viral hepatitis
3 DHepatitis B infection is transmitted via blood sexually or vertically Infection may be acute or chronic Diagnostic markers are the presence of surface antigen (HBsAg) and HBV DNA The presence of e antigen (HBeAg) indicates high infectivity Infected newborns have a 95 risk of becoming carriers this risk decreases with infection acquired later in childhood Approximately 15ndash25 of HBV carriers will die from cirrhosis or hepatocellular carcinoma Extrahepatic findings are more common in older children and include membranous glomerulonephritis and GianottiminusCrosti syndrome Fulminant hepatic failure occurs in severe cases resulting in persistent jaundice encephalopathy and coagulopathy Management includes counselling family members monitoring for ongoing liver disease and consideration of antiviral therapy
Further reAding
Brandt O abeck d Gianotti r Burgdorf W Gianotti crosti
syndrome J Am Acad Dermatol 2006 54 136ndash145
slowik mK Jhaveri r hepatitis B and c viruses in infants and
young children Semin Pediatr Infect Dis 2005 16 296ndash305
Case 31 CHypercalcaemia is uncommon in infancy The most common symptoms in this age group are irritability vomiting and constipation It may be a manifestation of Williams syndrome vitamin D or calcium excess as well as disorders associated with reduced bone formation such as hypophosphatasia or increased bone resorption such as malignancy Occasionally
Paediatrics and child health 184 205 copy 2008 elsevier ltd all rights reserved
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-
SympoSium neonatology
Control of the thermal environment is important for all babies but it is the unwell immature babies who present the greatest challenge They are usually nursed either in an incubator or on an open platform under a radiant heater The early clinical trials of Silverman and others showed that the use of incuba-tors to keep babies warm improved outcome There have never been any controlled studies that show that radiant heaters are as effective clinically Babies nursed with similar skin temperatures have a higher basal metabolic rate when managed under radi-ant heaters compared with incubators26 However no study has shown any significant difference in outcome for babies nursed using either of these devices although Meyer et al27 reported a non-significant trend to better outcome in babies nursed under a radiant heater
Transepidermal water loss
Silverman in the 1950s showed that babies are better able to maintain their body temperature in a humid environment com-pared with a dry environment28
In the 1970s it became possible to measure the evaporation rate of water from the skin surface29 Transepidermal water losses (TEWL) are high in the immature baby At 26 weeksrsquo gestation on day 1 of life the baby can lose over 50 kcalkg by evapora-tion compared with less than 5 kcalkg in the term infant30 Data from Hammerlund et al30 suggest that the skin matures rapidly after birth and adult losses are reached around 10 d of age in all babies After this time the major source of heat loss in all babies is from radiation More recently others have shown that in the very immature baby the maturation of the skin may take longer and 30 weeksrsquo corrected age is a better estimate of the time taken to reach adult TEWL31 In practical terms the amount of trans-epidermal fluid losses after about 14 d are unlikely to remain a major problem
Evaporative water loss from the skin depends on the ambi-ent water vapour pressure irrespective of how the baby is being nursed The high rate of evaporation during care under a radiant heater is due to the low ambient water vapour pressure and not any direct effect of non-ionizing radiation on the skin32
TEWL results in loss of both heat and fluid Under a radi-ant heater the temperature of the baby is maintained because of radiant heat gain but the large fluid losses can be a seri-ous problem Various interventions can help reduce evaporative fluid losses mainly from the skin but also from the respiratory tract
IncubatorsWithin an incubator it is relatively easy to raise the ambient water vapour pressure by introducing humidity within the can-opy The use of a relative humidity of 80 for the first 7ndash10 d of life significantly reduces TEWL in even the most immature infant30 Modern designs use a sealed water system to produce the humidity minimizing the concerns about possible increased infection risk in humidified incubators
Opening the incubator portholes results in a rapid fall in humidity although the air temperature within the canopy is maintained The handling of babies within incubators has been shown to be associated with increased thermal stress33 and it is likely that this is due to the fall in environmental humidity
paeDiatRiCS anD CHilD HealtH 184 15
resulting in increased evaporative heat losses Increasing the air temperature will compensate for the heat loss but incubators are relatively slow to respond to such changes
High humidity within the incubator can cause lsquorain outrsquo on the inside of the canopy This is caused by water condensing on the cold walls and can be minimized by ensuring an adequate environmental temperature within the nursery (around 28 degC)
Radiant heatersTEWL is the major problem in babies nursed under radiant heaters A shield or plastic blanket can be used to cover the baby and create a humidified microenvironment Warm humid-ified air can be passed under the shield or blanket but care must be taken to control the temperature and to make sure it does not affect the skin servo probe attached to the baby If the cover is removed the humidity falls rapidly and the baby starts to lose large amounts of fluid The radiant heater will compen-sate for any fall in the babyrsquos temperature but fluid losses are a concern
Maintenance of skin integrityDamage to the fragile skin of the preterm baby occurs easily and results in a significant increases both in TEWL and the risk of infection Maintaining skin integrity is very important and any adhesives on the skin should be kept to a minimum
Skin coveringsTransparent adhesive dressings on the skin reduce fluid loss but cause significant damage making them impractical
Use of semipermeable non-adhesive dressings lowers TEWL and reduces the bacteria number in the covered skin34 In a ran-domized controlled trial in infants less than 1000 g the skin cov-ered with a semipermeable membrane was in better condition but there were no significant differences in fluid requirements or electrolyte status35
Emollients are used to cover the skin and prevent fluid loss They have been shown to be safe and do not cause burns when exposed to radiant heat or phototherapy Their use reduces excessive drying skin cracking and fissuring However the effect of these products wears off after about 3 h necessitating repeated application36 Treated infants had better skin scores and there were no differences in bacterial skin counts fungal counts or colonization patterns or fluid requirements and electrolyte status37
Ventilator humidityThere can be high fluid and heat losses from the respiratory tract of the ventilated baby It is important to use adequate humidifi-cation in all ventilator circuits
PhototherapyThe effect of phototherapy on TEWL is variable No change was found in a group of thermally stable infants38 yet others have reported an increase in TEWL despite skin temperature and rela-tive humidity remaining unchanged39 Rather than increase fluid intake just because phototherapy has been started fluid balance should be individually monitored and adjusted if necessary
Modern phototherapy units produce little heat but there is still some increase in the temperature of the top of the incubator
7 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
canopy This will reduce radiative heat losses and the incubator air temperature may have to be reduced to prevent a rise in the babyrsquos temperature
Transepidermal water loss and skin maturationTransepidermal movement of water is essential for the acceler-ated maturation of the skin of the immature baby40 It also helps in maintaining the epidermal barrier function41
Use of high ambient humidity in nursing preterm babies under 28 weeksrsquo gestation has been shown to reduce the rate of promo-tion of skin barrier development42
More work in the immature baby is needed to determine the optimum level and duration of environmental humidity as well as the associated benefits and risks of use and the effects of humidification on clinically important outcomes43
Temperature monitoring and its interpretation
The concept of the neutral thermal environment in which a baby uses a minimum of energy to maintain thermal stability has proven useful in determining the optimum environmental temperature for nursing the newborn baby4445 The published data are now old and do not include any allowance for added humidity This makes them less useful in the care of the very immature baby
The way a baby interacts with their environment is always changing and whatever settings are first used it is necessary to monitor continuously the thermal balance Continuous mea-surement of oxygen consumption to allow calculation of energy expenditure is not practical and in normal day-to-day care tem-perature monitoring is the only means of assessing the thermal stability of the baby
There is no single deep body temperature as this will vary depending on the metabolic rate of a particular tissue The brain has the highest temperature of any organ within the body It is however possible to find a central temperature that is representa-tive of deep body temperature Trends in this temperature reflect changes in the deep body temperatures of the body at least with sufficient accuracy for day-to-day clinical care
Traditionally rectal temperature has been used as the mea-sure of deep body temperature This is still used commonly in many countries but less so in UK There is a significant risk of damage to the mucosa of the rectum Also rectal temperature is unreliable being affected by the depth of insertion of the ther-mometer whether the baby has just passed a stool and by the temperature of the blood returning from the lower limbs It is difficult to retain the probes in the same position making this an unreliable site for continuous temperature monitoring
The temperature in the oesophagus at the level of the heart gives a measure of the temperature of the blood in the great veins returning from the body This is possibly the best overall representation of the lsquodeep body temperaturersquo Measurement of oesophageal temperature is however very invasive and not suit-able for clinical monitoring
The temperature of the skin over the liver or in the axilla reflects central temperature Actual values will be lower than the deep body temperatures but in the immature baby these sites can be used to show the trend in central temperature A more accurate measurement can be obtained by placing the
paeDiatRiCS anD CHilD HealtH 184 15
probe between the scapulae and a non-conducting mattress No tape is needed on the skin as the baby lies on the probe holding it in place If the probe is over an area of skin from which no heat can be lost by conduction convection radia-tion or evaporation then with heat flow from the centre of the body to the skin down a temperature gradient this area of skin will warm up to the same temperature as the bodyrsquos core This so-called zero heat flux temperature has been shown to be very close to the central temperature as measured by an oesophageal probe46
The measurement of a single temperature tells us how well the baby is maintaining that temperature but nothing about how much energy is being used to achieve thermal balance The continuous measurement and display of a central (abdominal axilla or zero heat flux) and a peripheral (sole of the foot) tem-perature detects cold stress with the peripheral temperature fall-ing before the central measurement changes
The preterm baby who appears to be comfortable in their environment will have a central temperature measured from a skin probe of 368ndash373 degC and a centralndashperipheral temperature difference of 05ndash1 degC An increasing centralndashperipheral tempera-ture difference particularly above 2 degC is usually due to cold stress and occurs before any fall in central temperature12
Hypovolaemic babies will vasoconstrict their peripheral circu-lation in an attempt to maintain blood pressure This results in an increase in the centralndashperipheral temperature difference but in such cases there are usually other signs of hypovolaemia such as rising heart rate and falling blood pressure12
A high central temperature particularly if unstable along with a wide centralndashperipheral gap is seen in septic babies47
Conclusion
Although we have known for a very long time the importance of maintaining the temperature of the newborn we are still faced with new challenges in the care of the sick immature baby Tem-perature control during their period of adaptation to extrauterine life is often poor and allowing these vulnerable babies to cool is associated with adverse outcome Simple measures can prevent hypothermia following delivery If cold at birth is associated with poor outcome there is no reason to believe that preventing ther-mal stress is any less important once the baby is in the neonatal unit It is important that the risks and benefits associated with various methods of controlling the infantrsquos temperature are fully understood
RefeRenCeS
1 Cone te perspectives in neonatology in Sith gF Vidyasagar D eds
Historical Review and Recent advances in neonatal and perinatal
medicine mead Johnson nutritional Division 1983 p 9ndash33
2 Silverman Wa Fertig JW Berger ap the influence of the thermal
environment upon survival of newly born preterm infants Pediatrics
1958 22 876ndash885
3 Silverman Wa agate FJ Fertig JW a sequential trial of the
nonthermal effect of atmospheric humidity on survival of human
infants of low birth weight Pediatrics 1963 31 710ndash724
8 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
4 Costeloe K Hennessy e gibson at marlow n Wilkinson aR for the
epiCure Study group the epiCure study outcomes to discharge
from hospital for infants born at the threshold of viability Pediatrics
2000 196 659ndash671
5 CeSDi project 2728 available from wwwcemachorguk
publicationsp2728mainreportpdf
6 parry g tucker J tarnow-mordi W for the uK neonatal Staffing
Study Collaborative group CRiB ii an update of the clinical risk
index for babies score Lancet 2003 361 1789ndash1791
7 Richardson DK Corcoran JD escobar gJ et al Snap-ii and Snappe-ii
simplified newborn illness severity and mortality risk scores
J Pediatr 2001 138 92ndash100
8 Wyatt JS gluckman pD liu py et al CoolCap Study group
Determinants of outcomes after head cooling for neonatal
encephalopathy Pediatrics 2007 119 912ndash921
9 yager Jy armstrong ea Jaharus C Saucier Dm Wirrell eC preventing
hyperthermia decreases brain damage following neonatal-ischemic
seizures Brain Res 2004 1011 48ndash57
10 Harned Jr HS Herrington Rt Ferreiro Ji the effects of immersion
and temperature on respiration in newborn lambs Pediatrics 1970
45 598ndash605
11 laptook aR Salhab W Bhaskar B neonatal Research network
admission temperature of low birth weight infants predictors and
associated morbidities Pediatrics 2007 119 e643ndash649
12 lyon aJ pikaar me Badger p mcintosh n temperature control in
infants less than 1000g birthweight in the first 5 days of life Arch
Dis Child 1997 76 F47ndash50
13 Vohra S Roberts RS Zhang B Janes m Schmidt B Heat loss
prevention (Help) in the delivery room a randomized controlled
trial of polyethylene occlusive skin wrapping in very preterm infants
J Pediatr 2004 145 750ndash753
14 lyon aJ Stenson B Cold comfort for babies Arch Dis Child Fetal
Neonatal Ed 2004 89 F93ndash94
15 Stothers JK Head insulation and heat loss in the newborn Arch Dis
Child 1981 56 530ndash534
16 newton t Watkinson m preventing hypothermia at birth in
preterm babies at a cost of overheating some Arch Dis Child Fetal
Neonatal Ed 2003 88 F256
17 Smith Cl Quine D mcCrosson F armstrong l lyon a Stenson B
Changes in body temperature after birth in preterm infants
stabilised in polythene bags Arch Dis Child Fetal Neonatal Ed 2005
90 F444
18 mcCall em alderdice Fa Halliday Hl Jenkins Jg Vohra S
interventions to prevent hypothermia at birth in preterm andor low
birthweight babies Cochrane Database of Systematic Reviews 2005
issue 1 art noCD004210 doi10100214651858CD004210pub2
19 meyer mp Bold gt admission temperatures following radiant
warmer or incubator transport for preterm infants lt 28 weeks
a randomised study Arch Dis Child Fetal Neonatal Ed 2007 92
F295ndash297
20 Carmichael a mcCullough S Kempley St Critical dependence of
acetate thermal mattress on gel activation temperature Arch Dis
Child Fetal Neonatal Ed 2007 92 F44ndash45
21 Hey en the care of babies in incubators in gairdner D Hull D
eds Recent advances in paediatrics 4th edn london J amp a
Churchill 1971 p 171ndash216
22 Whitelaw a Heisterkamp g Sleath K acolet D Richard m Skin-to-
skin contact for very low birthweight infants and their mothers Arch
Dis Child 1988 63 1377ndash1381
paeDiatRiCS anD CHilD HealtH 184 15
23 Bauer K pyper a Sperling p uhrig C Versmold H effects of
gestational and postnatal age on body temperature oxygen
consumption and activity during early skin-to-skin contact between
preterm infants of 25ndash30-week gestation and their mothers Pediatr
Res 1998 44 247ndash251
24 Hey en Katz g orsquoConnell B the total thermal insulation of the
newborn baby J Physiol 1970 207 683ndash689
25 Hey en temperature regulation in sick infants in tinker J Rapin m
eds Care of the Critically ill patient Berlin Springer 1983 p
1013ndash1029
26 leBlanc mH Relative efficacy of an incubator and an open warmer
in producing thermoneutrality for the small premature infant
Pediatrics 1982 69 439ndash445
27 meyer mp payton mJ Salmon a Hutchinson C deKlerk a
a clinical comparison of radiant warmer and incubator care for
preterm infants from birth to 1800grms Pediatrics 2001 108
395ndash401
28 Silverman Wa Blanc Wa effect of humidity on survival of newly
born premature infants Pediatrics 1957 20 477ndash487
29 Hammarlund K Sedin g transepidermal water loss in newborn
infants iii relation to gestational age Acta Paediatr Scand 1979
68 795ndash801
30 Hammerlund K Stroumlmberg B Sedin g Heat loss from the skin of
preterm and fullterm newborn infants during the first weeks after
birth Biol Neonate 1986 50 1ndash10
31 Kalia yn nonata lB lund CH guy RH Development of skin
barrier function in premature infants J Invest Dermatol 1998 111
320ndash326
32 Kjartansson S arsan S Hammarlund K Sjoumlrs g Sedin g Water loss
from the skin of term and preterm infants nursed under a radiant
heater Pediatr Res 1995 37 233ndash238
33 mok Q Bass Ca Ducker Da mcintosh n temperature instability
during nursing procedures in preterm neonates Arch Dis Child
1991 66 783ndash786
34 mancini aJ Sookdeo-Drost S madison KC Smoller BR lane at
Semipermeable dressings improve epidermal barrier function in
premature infants Pediatr Res 1994 36 306ndash314
35 Donahue ml phelps Dl Richter Se Davis Jm a semipermeable skin
dressing for extremely low birth weight infants J Perinatol 1996 16
20ndash26
36 nopper aJ Horii Ka Sookdeo-Drost S Wang tH mancini aJ lane at
topical ointment therapy benefits premature infants J Pediatr 1996
128 660ndash669
37 pabst RC Starr Kp Qaiyumi S Schwalbe RS gewold iH the effect
of application of aquaphor on skin condition fluid requirements
and bacterial colonization in very low birth weight infants
J Perinatol 1999 19 278ndash283
38 Kjartansson S Hammarlund K Sedin g insensible water loss from
the skin during phototherapy in term and preterm infants Acta
Paediatr 1992 81 764ndash768
39 grunhagen DJ de Boer mg de Beaufort aJ Walther FJ
transepidermal water loss during halogen spotlight phototherapy in
preterm infants Pediatr Res 2002 51 402ndash405
40 Hanley K Jiand y elias pm Feingold KR Williams ml acceleration
of barrier ontogenesis in vitro through air exposure Pediatr Res
1997 41 293ndash299
41 Denda m Sato J masuda y et al exposure to a dry environment
enhances epidermal permeability barrier function J Invest Dermatol
1998 111 858ndash863
9 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
42 Aringgren J Sjoumlrs g Sedin g ambient humidity influences the rate of
skin barrier maturation in extremely preterm infants J Pediatr 2006
148 613ndash617
43 Sinclair l Sinn J Higher versus lower humidity for the prevention of
morbidity and mortality in preterm infants in incubators (protocol)
Cochrane Database Syst Rev 2007 issue 2 art noCD006472
doi10100214651858
44 Hey en Katz g the optimum thermal environment for naked
babies Arch Dis Child 1970 45 328ndash334
45 Sauer pJJ Dane HJ Visser HKa new standards for neutral thermal
environment of healthy very low birthweight infants in week one of
life Arch Dis Child 1984 59 18ndash22
46 Dollberg S Xi y Donnelly mm a noninvasive alternative to rectal
thermometry for continuous measurement of core temperature in
the piglet Pediatr Res 1993 34 512ndash517
47 messaritakis J anagnostakis D laskari H Katerelos C Rectal-skin
temperature difference in septicaemic newborn infants Arch Dis
Child 1990 65 380ndash382
paeDiatRiCS anD CHilD HealtH 184 16
Practice points
bull Hypothermia in the newborn infant is associated with adverse
outcome
bull Despite improvements in technology the preterm baby is still
at high risk of hypothermia immediately after delivery
bull prevention of evaporative heat losses eliminates hypothermia
at resuscitation
bull High evaporative fluid losses must be prevented if the baby
is nursed under a radiant heater
bull more studies are needed to determine the optimum
management after delivery and to show if reducing
transepidermal water loss has an effect on the rate of skin
maturation
bull Continuous monitoring and display of a central and peripheral
temperature gives early warning of developing cold stress
0 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemiaJ m Hawdon
Abstractat birth the newborn baby undergoes many adaptive changes to inde-
pendent extrauterine life these include the changes of metabolic adap-
tation which must be understood in order to identify and manage the
conditions in which metabolic adaptation is delayed impaired or fails
resulting in low levels of glucose and other metabolic fuels which in turn
affect neonatal neurological function and if prolonged and severe cause
potential adverse outcome Babies identified as at risk of impaired met-
abolic adaptation must undergo clinical monitoring including accurate
blood glucose monitoring tailored to their condition Babies who present
with abnormal clinical signs in association with a low blood glucose level
must be investigated for underlying cause and treated promptly preven-
tion and treatment of clinically significant hypoglycaemia must be planned
to avoid compromising successful establishment of breast feeding
Keywords alternative fuels blood glucose breast feeding neonatal
metabolic adaptation operational thresholds risk factors
Introduction
At birth the newborn baby undergoes many adaptive changes to independent extrauterine life These include the changes of met-abolic adaptation essential to ensure energy provision to vital organs and then to sustain growth and further development The changes involved in metabolic adaptation must be understood in order to identify and manage the conditions in which metabolic adaptation is delayed impaired or fails The clinical outcome of these circumstances is usually referred to with the single short-hand diagnostic term lsquoneonatal hypoglycaemiarsquo However as will be illustrated in this article it is not appropriate to ascribe a diagnostic label to neonatal hypoglycaemia first because glucose is not the only fuel in the neonatersquos fuel economy and second because hypoglycaemia is the consequence of a number of vari-ous underlying disorders and thus does not in itself warrant a diagnostic label
There have been extensive studies of metabolic adaptation in human neonates and neonatal non-human mammals The latter studies have identified those mammals most similar to humans
J M Hawdon MA MBBS MRCP FRCPCH PhD is Consultant Neonatologist and
Honorary Senior Lecturer at UCL EGA Institute for Womenrsquos Health
Elizabeth Garrett Anderson and Obstetric Hospital University College
London Hospitals NHS Foundation Trust Huntley Street London UK
paeDiatRiCS anD CHilD HealtH 184 161
in terms of metabolic adaptation and sought to compare nutri-tionally comparable time frames eg suckling versus weaning periods Whilst the processes of metabolic adaptation are well described in term and preterm human neonates there are few if any clinical studies in human neonates of sufficient rigour to provide evidence for the circumstances in which brain injury may occur and thus it is not possible to provide evidence-based guide-lines for the prevention and management of clinically significant hypoglycaemia Therefore recommendations in this article and in the referenced review articles by recognized experts remain pragmatic and urge clinicians to individualize management for each baby placing heavy emphasis on careful clinical evaluation rather than single numerical definitions of brain-injuring hypogly-caemia and on detecting and treating underlying pathologies1ndash6
Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
During intrauterine life the fetus receives via the placenta a con-stant supply of nutrients initially for growth but in the third tri-mester also for storage Glucose crosses the healthy placenta at a rate of approximately 5 mgkgmin In addition to that required for basal fetal metabolism glucose is converted to glycogen which is stored in the liver cardiac muscle and central nervous system In the third trimester excess glucose is converted to tri-glycerides which are stored in adipose tissue
Insulin is an important fetal hormone to ensure glucose and other substrates are utilized for growth and storage but in nor-mal circumstances insulin is not required for fetal glucose con-trol The exception is for the infant of the mother with poorly controlled diabetes when transfer of glucose across the placenta is at a higher rate driven by the maternalndashfetal concentration gra-dient This results in increased insulin secretion excess growth and increased storage of glycogen and adipose tissue (macroso-mia) along with increased risk of intracellular hypoxia
Conversely in the fetus affected by severe placental insuffi-ciency transfer of glucose and other nutrients across the placenta is at a lower rate and the fetus is required to metabolize first its own fuel stores and then structural proteins (eg in muscle) to ensure energy delivery to the vital organs assisted by the redis-tribution of blood flow to these organs Should placental function deteriorate further these adaptive responses fail Fetal hypogly-caemia has been described in these circumstances78
When placental nutrition abruptly ceases at birth the healthy neonate is dependent upon endocrine changes to initiate meta-bolic adaptation Insulin levels fall steadily and the action of any residual circulating insulin is overcome by the surge of the coun-ter-regulatory hormones glucagon and the catecholamines This change in the balance of glucoregulatory hormones induces the activity of key enzymes for glycogenolysis (release of glucose from glycogen stores) gluconeogenesis (production of glucose from precursors including glycerol and amino acids) lipolysis (release of free fatty acids and glycerol from adipose tissue stores) and beta-oxidation of fatty acids to produce ketone bodies910 If fasting is prolonged structural protein is broken down to release gluconeogenic amino acids Other than lipolysis and proteolysis all of these processes take place in the liver Glycogenolysis also takes place in cardiac muscle and the central nervous system providing immediate energy (in the form of glucose or lactate)
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
at this crucial time411 Clearly during this catabolic phase of immediate postnatal nutrition prior to the establishment of suck-ling feeds provision of energy for vital organ function is at the expense of growth and fuel storage
The postnatal metabolic transition is characterized by low cir-culating blood glucose concentrations compared to those of older infants and children often for a number of days12 This is almost always of no pathological significance for a number of reasons including differences in the function and metabolic requirements of the brain and importantly the production and utilization of alter-native fuels lactate and ketone bodies which are in plentiful supply in the neonate341213ndash20 An important finding from clinical studies and of clinical relevance to those caring for mothers and babies is that in all groups of infants studied to date those who are breast fed have higher circulating ketone body levels than those who are formula fed even after correcting for blood glucose levels102122
There are circumstances however when hypoglycaemia is severe and prolonged and conditions when alternative fuel pro-duction is also impaired or fails In these circumstances low blood glucose levels do acquire clinical significance The key metabolic processes and the risk factors for impaired metabolic adaptation are summarized in Table 1
Metabolic changes at birth ndash key hormones and metabolic processes and risk factors for impaired metabolic adaptation
Postnatal metabolic
changes
Risk factors
Hormones
insulin falls neonatal hyperinsulinism ndash infant of
diabetic mother or idiopathic
glucagon surge possibly blunted by iv glucose or
formula feeds
Catecholamine surge maternal beta-blocker medication
(Cortisol ndash weak effect) (pituitary or adrenal insufficiency)
Metabolic processes
glygogenolysis preterm intrauterine growth
restriction (iugR) ndash reduced stores
perinatal hypoxia-ischaemia ndash stores
utilized
Hyperinsulinism
maternal beta-blocker medication
glycogen storage disorders
gluconeogenesis Hyperinsulinism
maternal beta-blocker medication
Hepatic dysfunction
Very rare inborn errors of metabolism
lipolysis preterm iugR ndash reduced stores
Hyperinsulinism
maternal beta-blocker medication
Ketogenesis Defects of beta-oxidation of fatty
acids
Hepatic dysfunction
Table 1
paeDiatRiCS anD CHilD HealtH 184 16
Impaired metabolic adaptation
Risk factors for impaired metabolic adaptation vary and may be related to any of the following reduced body fuel stores failure of the normal endocrine changes at birth systemic illnesses which impede function of the liver where the key metabolic processes occur or rarely inborn errors of metabolism (see Table 1)
It is well recognized that significant hypoglycaemia will result in a reduced level of consciousness andor fits However it is always important to be alert for detect and treat an underlying pathology which could be causing both the hypoglycaemia and the abnormal signs Often abnormal signs and hypoglycaemia are co-morbidities eg a primary neurological problem causes both abnormal neurological signs and hypoglycaemia secondary to poor feeding For this reason all possible underlying causes for presentation with hypoglycaemia must be considered and investigations planned accordingly Investigations for inborn errors of metabolism and endocrine disorders are most informa-tive if carried out when blood glucose levels are low
There have been extensive efforts to use data from clinical stud-ies of the human neonate to determine the significance of neonatal hypoglycaemia in terms of neurophysiological neurodevelopmental and neuroradiological sequelae However there are major difficul-ties in interpreting these clinical studies as to date these have been flawed by confounding factors such as immaturity placental insuf-ficiency and co-existing complications by heterogeneity of subjects and by failure to take into account protective mechanisms11423 The evidence from both animal and human studies suggests lsquopurersquo hypo-glycaemic brain injury is rare and for hypoglycaemic brain injury to occur there must be co-existing failure of metabolic adaptation such that alternative fuels are not available There is no evidence that lsquotransitionalrsquo hypoglycaemia in the healthy neonate is associated with acute or long term sequelae and indeed even for babies in the at-risk groups on many occasions protective factors will prevail
Diagnosis of clinically significant hypoglycaemia
lsquoNeonatal hypoglycaemiarsquo is a commonly cited diagnosis most often based on a single blood glucose level and using inaccurate methods of measurement and with disregard for the presence or absence of associated clinical signs In the many published texts and local guidelines there is no consistency of approach For this reason a multinational group of experts attempted to examine critically the evidence on which clinical recommendations should be made1 Fol-lowing detailed analysis the authors considered it impossible to define hypoglycaemia as a single blood glucose level and instead suggested operational thresholds and therapeutic goals They con-cluded that low blood glucose levels accompanied by neurological signs should be investigated and treated regardless of the blood glu-cose level They also pragmatically concluded that a blood glucose level below 10 mmollitre should be treated immediately In babies who are at risk of impaired metabolic adaptation but who have no clinical signs it is recommended that interventions to raise blood glucose level are considered if blood glucose levels are persistently below 20 mmollitre For sick and very low birthweight babies who are likely to have a requirement for intravenous glucose there should be a lsquotherapeutic goalrsquo to maintain blood glucose levels above 25 mmollitre Where there is known hyperinsulinism (a very high-risk condition characterized by high intravenous glucose
2 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
requirements to maintain normoglycaemia) an operational thresh-old and therapeutic goal of 35 mmollitre has been proposed24
Finally there must be careful consideration of the infant of the diabetic mother In extreme and rare cases there may be signifi-cant but transient hyperinsulinism and in these cases the thera-peutic goal must be 35 mmollitre More commonly babies whose mothersrsquo diabetes has been well controlled will have normal lsquotran-sitional hypoglycaemiarsquo or slightly delayed metabolic adaptation while insulin levels fall postnatally There must be careful and repeated clinical assessment including blood glucose monitoring For infants of diabetic mothers who have no evidence of signifi-cant hyperinsulinism and no abnormal clinical signs there is no evidence that the operational threshold for hyperinsulinism must be applied Indeed to do so would result in separation of large numbers of healthy babies from their mothers with the conse-quent impact upon breast feeding and resource allocation25
The operational thresholds for various groups of babies are summarized in Table 2
The guidance relating to operational thresholds is predicated upon the accurate measurement of blood glucose levels It is now well known that the commonly used reagent strips are insufficiently accurate to diagnose hypoglycaemia and monitor at-risk infants and there must be access to equipment which allows immediate and accurate determination of blood glucose levels1426ndash28
Blood glucose monitoring
An accurate method for blood glucose monitoring must be employed as described above The sample should be free flowing venous or from a warm heel such that the blood flows freely without squeezing
Blood of high haematocrit often yields low blood glucose lev-els because of dilution of glucose by red cell water However this is also clinically relevant because polycythaemia is itself a high-risk situation Therefore in polycythaemic infants both the haematocrit and blood glucose level must be monitored and both acted upon accordingly
Operational thresholds for blood glucose levels in the management of babies at risk of impaired metabolic adaptation124
Clinical condition Blood glucose level at which
to consider intervention and
therapeutic goal
all at-risk babies lt10 mmollitre
abnormal neurological
signs
intervene regardless of blood
glucose levelSystematically unwell baby therapeutic goal of 25 mmollitre
at-risk babies no abnormal
neurological signs
persistently lt20 mmollitre
Hyperinsulinism 35 mmollitre
Table 2
paeDiatRiCS anD CHilD HealtH 184 163
Only babies in at-risk groups or babies who have abnormal neurological signs should be subjected to blood glucose monitor-ing (Table 3)
It is important not to commence blood glucose monitoring too soon after birth as to do so would fail to differentiate the baby with incipient hypoglycaemia from the baby undergoing the nor-mal postnatal fall in blood glucose level It is recommended in the otherwise healthy but at-risk baby to wait until around 3 h after birth to make the first blood glucose estimation2528 In prac-tice this is usually before the second feed assuming best practice of offering a baby a breast (or if necessary formula feed) imme-diately after birth Clearly if the baby is unwell or has abnormal clinical signs in the first 3 h they will be treated according to clinical condition which will include intravenous fluids and the therapeutic goal described above would apply
Similarly the temptation to measure blood glucose level shortly (within 2 h) after intravenous glucose has been discon-tinued must be avoided In this circumstance as at birth blood glucose levels fall and then subsequently rise in response to coun-ter-regulation It is this effective rise which must be assessed by blood glucose measurement at least 2 h after a change is made (provided the baby remains clinically well)
Blood glucose levels rise after a feed and fall to a nadir before the subsequent feed As our concern is the lowest blood glucose level during the feed cycle and as this measurement may assist in determining best feed frequency it is important that pre-feed blood glucose concentration is measured There is no clinical value in measuring a post-feed blood glucose level as this may be falsely reassuring and this practice subjects babies to more frequent heel pricks or venesections than is necessary
Finally consideration must be given to when to discontinue blood glucose monitoring This will depend upon the babyrsquos clin-ical condition feeding pattern and underlying disorder or risk factors for impaired metabolic adaptation
Prevention and management of clinically significant hypoglycaemia
In babies at risk of clinically significant hypoglycaemia and who are well enough to tolerate enteral feeds milk feeds are the
At-risk babies for whom blood glucose monitoring is recommended
abnormal neurological signs
Systemically unwell eg suspected or proven infection
hypoxicndashischaemic encephalopathy
preterm (lt 37 weeks)
intrauterine growth restriction (lt 2nd centile and any baby with
signs of wasting)
infant of diabetic mother
polycythaemia
maternal beta-blocker medication
Suspected hyperinsulinism
Suspected inborn error of metabolism or endocrine disorder
Table 3
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
mainstay of prevention For babies who are able to feed orally breast feeding should be first choice and there must be maximal support for the mother to do so This is a key clinical priority for midwives and paediatricians
If there are concerns regarding adequacy of breast feeding to prevent hypoglycaemia the mother should be encouraged to commence expression of milk from very soon after birth If there is insufficient breast milk to prevent babies reaching the opera-tional thresholds described above there should be judicious use of formula milk using only the smallest amount required to keep the babyrsquos glucose in the required range Formula milk in exces-sive quantities has been demonstrated to suppress normal meta-bolic adaptation2122
In babies for whom early enteral feeds are not appropriate or not tolerated or for whom enteral feeding does not prevent blood glucose level falling below operational thresholds intravenous glucose infusion at rates around 4ndash5 mgkgmin (58ndash72 mlkgd of 10 dextrose) are usually sufficient to prevent hypoglycae-mia If blood glucose levels remain below therapeutic goals the rate of infusion may be steadily increased Excess glucose infu-sion over and above that required to maintain the therapeutic goal will stimulate insulin and there is a risk of rebound hypo-glycaemia if high rate glucose infusions are too rapidly reduced Milk feeds if tolerated should be continued if intravenous glu-cose is commenced
If infused volume of glucose solution becomes excessive in order to maintain therapeutic goals or if fluid restriction must be applied more concentrated glucose concentrations must be infused through a central venous line This is particularly rel-evant to the hyperinsulinaemic baby in whom glucose infusion rates in excess of 8ndash10 mgkgmin are required to maintain ther-apeutic goals There is a high risk of severe and brain-damaging hypoglycaemia if treatment is delayed or fails to raise blood glu-cose levels and management of these babies requires consulta-tion with or referral to a specialist centre24
If there is presentation of hypoglycaemia with abnormal clinical signs or a very low blood glucose level (less than 1 mmollitre) this mandates urgent treatment with intravenous glucose The rates of glucose infusion described above are usually sufficient to bring the blood glucose level rapidly to the therapeutic goal without a bolus of glucose being necessary In fact a bolus dose of glucose will result in a peak blood glucose level and then an insulin surge making subsequent management problematical This is minimized by the use of a lsquomini-bolusrsquo should a bolus of glucose be required ndash 200 mg glucosekg (2 mlkg of 10 dextrose)28 Indications for mini-bolus are infants presenting with fits or coma or an lsquounre-cordablersquo or zero blood glucose level A mini-bolus should always be followed with glucose infusion or an increased glucose infusion rate if a baby already receiving intravenous glucose has required a mini-bolus
The temptation to supplement enteral feeds with glucose polymers and energy supplements (eg Duocal) or to use oral glucose gels or solutions (eg Hypostop) should be avoided as this carries a risk of necrotizing enterocolitis is likely to suppress normal metabolic adaptation and will suppress the appetite of the baby for effective oral feeding
Finally there are additional medications which may be employed in specific circumstances (Table 4) More detailed descriptions are given elsewhere242728 Babies who have hypoglycaemia which
paeDiatRiCS anD CHilD HealtH 184 164
is difficult to control by the measures described above and who require these additional treatments should be cared for in a centre which has expertise in metabolic and endocrinological conditions
Summary
Much controversy and confusion has surrounded neonatal hypo-glycaemia but this usually arises as a result of failure to under-stand the processes of normal metabolic adaptation and the fact that hypoglycaemia is a presenting sign rather than a diagnosis in itself Plans for investigation and management must be based upon the most likely underlying cause of impaired metabolic adaptation and take into account the clinical condition of the baby This is counter to the current trend to propose rigid pro-tocols and algorithms and re-introduces the value of detailed clinical evaluation and decision making The mainstay of man-agement is close clinical observation of vulnerable infants and energy provision tailored to their individual needs whilst avoid-ing excessively invasive management (namely unnecessary sep-aration of mother and baby routine or excessive formula milk supplementation or intravenous glucose administration) which themselves inhibit protective metabolic responses and impede successful establishment of breast feeding
ReFeRenCeS
1 Cornblath m Hawdon Jm Williams aF et al Controversies regarding
definition of neonatal hypoglycemia Suggested operational
thresholds Pediatrics 2000 105 1141ndash1145
2 Cornblath m ichord R Hypoglycemia in the neonate Semin
Perinatol 2000 24 136ndash149
3 Vannucci RC Vannucci SJ Hypoglycaemic brain injury Semin
Neonatol 2001 6 147ndash155
4 Rozance pJ Hay WW Hypoglycaemia in newborn infants features
associated with adverse outcomes Biol Neonate 2006 90 74ndash86
5 Hawdon Jm Hypoglycaemia in newborn infants defining the
features associated with adverse outcomes ndash a challenging remit
Biol Neonate 2006 90 87ndash88
6 Williams aF neonatal hypoglycaemia clinical and legal aspects
Semin Fetal Neonatal Med 2005 10 363ndash368
7 Soothill pW nicolaides KH Campbell S prenatal asphyxia
hyperlacticaemia hypoglycaemia and erythroblastosis in growth
retarded fetuses BMJ 1987 294 1051ndash1053
Additional medication in specific conditions (if these are required there must also be referral to a specialist centre)
Medication Indication
glucagon intramuscular bolus dose of 200 μgkg
transient rise in blood glucose level eg
when difficulty re-siting intravenous infusion
Diazoxide Hyperinsulinism
Hydorcortisone pituitary or adrenal insufficiency
Table 4
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
8 Hawdon Jm Ward platt mp mcphail S Cameron H Walkinshaw Sa
prediction of impaired metabolic adaptation by antenatal Doppler
studies in small for gestational age fetuses Arch Dis Child 1992
67 787ndash792
9 Deshpande S Hawdon Jm et al adaptation to extrauterine life in
Rodeck C Whittle m eds Fetal medicine Basic Science and Clinical
practice edinburgh Churchill livingstone 1999
10 Ward platt m Deshpande S metabolic adaptation at birth Semin
Fetal Neonatal Med 2005 10 341ndash350
11 eyre Ja Stuart ag Forsyth RJ Heaviside D Bartlett K glucose
export from the brain in man evidence for a role for astrocytic
glycogen as a reservoir of glucose for neural metabolism Brain Res
1994 28 349ndash352
12 Hawdon Jm Ward platt mp aynsley-green a patterns of metabolic
adaptation for preterm and term infants in the first neonatal week
Arch Dis Child 1992 67 357ndash365
13 Hawdon Jm Ward platt mp aynsley-green a prevention and
management of neonatal hypoglycaemia Arch Dis Child Fetal
Neonatal Ed 1994 70 F60ndash64
14 Hawdon Jm Hypoglycaemia and the neonatal brain Eur J Paediatr
1999 158 S9ndash12
15 massieu l Haces ml montiel t Hernaacutendez-Fonseca K acetoacetate
protects hippocampal neurons against glutamate-mediated neuronal
damage during glycolysis inhibition Neuroscience 2003 120
365ndash378
16 yamada Ka Rensing n thio ll Ketogenic diet reduces
hypoglycaemia-induced neuronal death in young rats Neurosci Lett
2005 385 210ndash214
17 nehlig a Brain uptake and metabolism of ketone bodies in animal
models Prostaglandins Leukot Essent Fatty Acids 2004 70
265ndash275
18 Hernaacutendez mJ Vannucci RC Salcedo a Brennan RW Cerebral blood
flow and metabolism during hypoglycemia in newborn dogs
J Neurochem 1980 35 622ndash628
19 Vannucci RC nardis ee Vannucci SJ Campbell pa Cerebral
carbohydrate and energy metabolism during hypoglycaemia in
newborn dogs Am J Physiol 1981 256 H1659ndashH1666
20 anwar m Vannucci RC autoradiographic determination of regional
cerebral blood flow during hypoglycaemia in newborn dogs Pediatr
Res 1988 24 41ndash45
21 Hawdon Jm Williams aF et al Formula supplements given to
healthy breastfed preterm babies inhibit postnatal metabolic
adaptation results of a randomised controlled trial Arch Dis Child
2000 82 a30
paeDiatRiCS anD CHilD HealtH 184 16
22 de Rooy l Hawdon Jm nutritional factors that affect the postnatal
metabolic adaptation of full-term small- and large-for gestational
age infants Pediatrics 2002 109 e42
23 Hawdon Jm Hypoglycaemia and brain injury ndash when neonatal
metabolic adaptation fails in levene m ed Fetal and neonatal
neurology and neurosurgery edinburgh Churchill livingstone in
press
24 Hussain K Congenital hyperinsulinism Semin Fetal Neonatal Med
2005 10 369ndash376
25 acolet D Diabetes in pregnancy Caring for the Baby after Birth
CemaCH 2007 2
26 Hussain K Sharief n the inaccuracy of venous and capillary blood
glucose measurement using reagent strips in the newborn period
and the effect of haematocrit Early Hum Dev 2000 57 111ndash121
27 Hawdon Jm Disorders of blood glucose homeostasis in the neonate
in Rennie Jm ed Robertonrsquos textbook of neonatology 4th edn
edinburgh Churchill livingstone 2005
28 Deshpande S Ward platt mp the investigation and management
of neonatal hypoglycaemia Semin Fetal Neonatal Med 2005 10
351ndash361
Practice points
bull identify risk factors for impaired metabolic adaptation
bull Clinical monitoring including accurate blood glucose
measurement for at-risk babies
bull Feed at-risk babies soon after birth and maintain thermal
homeostasis
bull take first blood glucose level at 3ndash4 h of age
bull intervene in at-risk baby with no clinical signs if two
consecutive blood glucose measurements lt 20 mmollitre
bull intervene in any baby with blood glucose measurement
lt 10 mmollitre
bull intervene in any baby with abnormal clinical signs regardless
of blood glucose level
bull investigate for underlying cause of failure of metabolic
adaptation
bull maintain lactation and breast feeding
5 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Resuscitation of the term and premature babyJonathan Wyllie
Abstractalthough most newly born babies establish normal respiration and
circulation without help up to 1minus2 may require some resuscitation
or stabilization Babies who do not establish adequate regular normal
breathing or who have a heart rate of less than 100 beatsmin or other
problems such as prematurity may require assistance the differences in
approach to the resuscitation of such babies originate in the physiology
and pathophysiology of acute asphyxia at birth However management
of airway and breathing remain the key features of resuscitation and
where cardiac depression has occurred this is nearly always due to hy-
poxia secondary to respiratory compromise therefore most babies will
respond within 2minus3 min of effective aeration of the lungs and the need
for intubation chest compressions or drugs is rare the international
liaison Committee on Resuscitation (ilCoR) evaluated evidence in 2000
and 2005 in order to provide guidelines for resuscitation they will do
so again for 2010 this evidence is limited in terms of both quantity and
quality and controversies still exist more research is needed to ensure
that our future actions are based upon evidence rather than history this
article will review the recommended approach to resuscitation as well as
some newer evidence
Keywords guidelines neonatal newborn premature resuscitation
Background
In the UK 669 601 babies were born alive in 2006 and most made the transition to extrauterine life without problems Those babies who did not establish adequate regular normal breathing or who had a heart rate of less than 100 beatsmin may have required assistance1 Factual evidence concerning the true requirement for resuscitation at birth is sparse Up to 10 of newborns may require some assistance to begin breathing with less than 1 needing extensive resuscitation2 However just because a baby received resuscitation does not necessarily mean that it was required and rates of intervention may be altered by educa-tion34 or the personnel present at deliveries5 In a UK tertiary centre with a standard approach to resuscitation at birth up to 12 of all babies received some airway assistance with just over 1 being intubated3 In Sweden only 1 of babies over 2500 g required mask or endotracheal tube ventilation at birth of which most responded to the former4
Jonathan Wyllie MBChB FRCPCH is Consultant Neonatologist at the James
Cook University Hospital Marton Road Middlesbrough TS4 3BW UK
paeDiatRiCS anD CHilD HealtH 184 16
Sometimes it is possible to predict babies who are likely to have respiratory depression at birth and to have appropriate per-sonnel present at delivery Guidelines for attendance at deliveries will vary with institution but even when almost 40 of deliv-eries are attended there may still be a further 15 of babies who require unexpected resuscitation5 a proportion that seems to remain whatever changes are made
The physiology of babies requiring help at birth has been summarized previously167 It allows a logical approach to resus-citation (Figure 1) when evidence is lacking and may prompt further research
Resuscitation at birth
PreparationAt birth resuscitation is more likely in babies with intrapartum evidence of significant fetal compromise those less than 35 weeksrsquo gestation those delivering vaginally by the breech and in multiple births Personnel trained in newborn resuscitation should be available at every delivery1 Someone experienced in tracheal intubation and advanced resuscitation should also be easily available for normal low-risk deliveries in hospital and ideally in attendance for deliveries with an increased likelihood of needing resuscitation In the latter cases the equipment and environment can be prepared beforehand including a discussion with the parents Wash your hands put on gloves and consider what help may be needed
Cord clampingAt birth it has long been known that delay in clamping the cord will lead to less anaemia in babies and reduce subsequent iron deficiency8 However few hospitals have practised this interven-tion due to worries about hypothermia and the need to resusci-tate or stabilize babies In developed countries the advantages seemed to be outweighed by the potential disadvantages A recent randomized controlled study of delayed clamping of the cord in premature babies found that the intervention group had less late-onset sepsis and fewer intraventricular haemorrhages9 This is a low-risk strategy which needs further evaluation in order to introduce it without increasing other risk factors in pre-mature deliveries
Assessment and temperature controlAssessment and temperature control for the newborn baby should occur at all deliveries The assessment indicates the need for resuscitation Babies may vary from 23 to 40+ weeksrsquo ges-tation and in weight from 500 to 5000 g They are born naked and wet and if left cannot cope with an environmental tem-perature of less than 32degC However if the term baby is imme-diately dried put skin-to-skin with the mother and covered the delivery room temperature can be as low as 25ndash28degC Obviously the smaller the baby the greater the surface area to mass ratio and the greater the risk of hypothermia Compromised babies are particularly vulnerable10 and hypothermia will lower oxygen tension11 increase metabolic acidosis12 and inhibit surfactant production13
An effective method of maintaining the temperature of prema-ture babies less than 28 weeksrsquo gestation is wrapping them with plastic before drying and then placing them under a radiant
6 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Dry the babyRemove any wet towels and cover
Start the clock or note the time
Give 5 inflation breathsLook for a response
If no increase in heart rate look for chest movement
Re-check head positionApply Jaw thrust
Repeat inflation breathsLook for a response
If no increase in heart rate look for chest movement
Try alternative airway opening manoeuvresRepeat inflation breaths
Look for a response
If no increase in heart rate look for chest movement
If the heart rate is not detectable or slow (lt60)Start compressions
3 compressions to each breath
Reassess heart rate every 30 secondsConsider venous access and drugs
Assess colour tone breathing and heart rate
Open the airway
If not breathing
If still not breathing
If no response
If still no response
When the chest is moving
If meconium present
Baby breathing wellDo not suction the airway
Baby floppy and not breathing wellConsider inspection and suction before
inflation breaths
Head in neutral position
Inflation breathsUse a well-fitting face mask
connedted to a
pressure-limited gas supply
Each breath 2ndash3 seconds
duration at 30 cm H2O for a
term baby
Get help from a second personto support the airway andor
inspect the oropharynx under
direct vision and consider
suction andor insert an
oropharyngeal airway
Chest compressionsCompvent ratio 31
Rate 120 events per minute
Ensure the chest moves with each ventilation breath
If breathingReassess heart rate and monitor baby
If heart rate is satisfactory but increasingContinue ventilation breaths at about 30 per
minute until baby is breathing adequately
If heart rate is satisfactory but increasingContinue ventilation breaths at about 30 per
minute until baby is breathing adequately
If heart rate is increasingStop compressions
Continue ventilation breaths at about 30 per
minute until baby is breathing adequately
If the chest is not movingRecheck head position and repeat inflation
breaths If competent consider intubation
If the chest is still not movingThe airway is the problem
Figure 1 newborn life support (Courtesy of the Resuscitation Council uK)
heater14 There is a small risk of hyperthermia so the temperature must be monitored carefully
An assessment is made of the babyrsquos colour tone respira-tions and heart rate127 The most important of these is heart rate and a stethoscope is more reliable than cord pulsation15 How-ever saturation monitors may offer a more reliable assessment of both heart rate and colour16 but their interpretation requires a detailed knowledge of normal saturations at birth at differing gestations A baby who is apnoeic and floppy in the absence of neurological disease is unconscious and likely to be in terminal apnoea however this does not change the initial approach other
paeDiatRiCS anD CHilD HealtH 184 167
than the need to summon help early APGAR scores are never calculated to guide resuscitation
Airway
If a baby is in primary apnoea then with an open airway the first gasp will start to aerate the lungs and most babies will be able to lsquoresuscitatersquo themselves as shown in physiological stud-ies on animals Neutral positioning of the babyrsquos head chin lift jaw thrust oropharyngeal airways and endotracheal intubation may all be helpful in certain situations if performed correctly17
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Endotracheal intubationThe placement of an endotracheal tube has long been the gold standard of airway control and this remains true in the unconscious baby if it is correctly sized placed and fixed in a timely manner However experience is directly related to effec-tiveness in endotracheal intubation1819 and the success rate of less experienced clinicians such as a resident (STA1-3) or a fel-low (STA3-5) is lower varying between 33 and 68 Even senior neonatologists often take longer than guidelines recom-mend19 Experienced clinicians may judge correct endotracheal position visually or by an increase in heart rate with the first breaths but detection of exhaled carbon dioxide will give more rapid confirmation in larger babies12171920 and this can be par-ticularly useful for less experienced clinicians or those supervis-ing them However not all systems for the detection of exhaled carbon dioxide work in the smallest premature infants
Laryngeal masksLaryngeal masks may be effective for ventilating term newborn babies but there are few data for small premature infants There have been reports of dislodged laryngeal airways during paedi-atric arrests when chest compressions have been administered Although success of placement at first attempt by paediatri-cians is greater with a laryngeal mask than with an endotra-cheal tube21 the only and small randomized controlled trial in the delivery room favoured endotracheal intubation when per-formed by an anaesthetist22 Based mainly upon case reports the laryngeal mask can be recommended when positioning and mask ventilation and endotracheal intubation have failed to secure the airway but not as yet as a primary method of airway control
MeconiumIn 2000 Wisewell et al23 reported a large randomized controlled trial showing that tracheal intubation and suctioning of meco-nium-stained but vigorous babies at birth did not reduce the incidence or severity of meconium aspiration syndrome More recently another randomized trial has now shown that suction-ing on the perineum similarly offers no benefit24 Neither of these practices is recommended but intubation and suction of meconium from the trachea of non-vigorous babies born through meconium-stained liquor is still recommended
Breathing
In the apnoeic baby the first breaths establish the resting lung volume and aerate the fluid-filled alveoli This mechanical effect aided by surface tension within the alveoli causes the initial fall in pulmonary vascular resistance Experimentally this effect occurs even if the lungs are ventilated with nitrogen but is increased when air is used presumably due to the vasodilator effect of 21 oxygen The mechanical stretching of the lung also triggers the activation of cyclo-oxygenase beginning the production of prostacyclin Bradykinin is produced which has a further direct vasodilator effect and also possibly via prostacyclin Therefore adequate airway control and passive ventilation is vital not only because babies requiring resuscitation at birth have an almost uniformly respiratory aetiology but also in order to promote post-natal adaptation and reverse any maladaptation
paeDiatRiCS anD CHilD HealtH 184 16
In term babies peak ventilatory pressures of 20ndash30 cmH2O may be required but the minimal pressure needed to achieve an improvement in heart rate should be used or if there is no response chest wall movement Longer breaths at lower pressure may be more effective in displacing alveolar fluid and establish-ing the resting lung volume in lungs with sufficient surfactant and may improve initial oxygenation However premature new-borns are obviously physiologically and anatomically less pre-pared for delivery than infants at term Over-inflation has been implicated in histological lung damage in animal models and high tidal volumes appear to be equally damaging whether given before or immediately after administration of surfactant How-ever the same effect is not seen if these excessive tidal volumes are delivered 15 min after administration of surfactant2526 It is now thought that both excess end expiratory volume and inad-equate end-expiratory volume may cause lung damage2728 In premature infants it would therefore seem sensible to use lower pressures of 20ndash25 cmH2O12 delivered in a controlled way to prevent over-inflation and to apply positive end-expiratory pres-sure (PEEP) to prevent damage from under-inflation PEEP also improves both lung compliance and gas exchange2930 Without PEEP the airways collapse during the expiratory phase in animal models of newborn resuscitation
If animal data can be extrapolated it would also seem appro-priate to give surfactant as soon as possible to premature babies in order to ameliorate damage2526
The majority of newborn infants requiring resuscitation will re-establish regular respiration after administration of a few breaths which may be due to Headrsquos paradoxical reflex by which the inflation triggers an inspiratory effort
VentilationOnce the lungs are aerated if the newborn remains apnoeic ventilation should be continued at 30ndash60 breathsmin avoiding hyperventilation and using the minimum pressure possible to maintain a heart rate greater than 100 beatsmin
Face mask the majority of infants who require ventilation receive it via a face mask This may be attached to a bagvalve system with a spring lsquoblow offrsquo system or a lsquoT-piecersquo with a set flow and pressure It is important to realize that the bagvalve system is flow sensitive and that the harder the operator presses the greater the flow and the higher the delivered pressure In fact 60 cmH2O can be achieved with vigorous squeezing of a self-inflating bag Therefore it may be advantageous that most opera-tors are unlikely to be as effective as they suppose in creating a seal with the mask31 This is a skill that requires tuition and prac-tice31 In delivering a set pressure T-piece systems such as the Tom Thumbcopy or Neopuffcopy perform better than any bagminusvalve system but require a gas supply There is no evidence that lung compliance can be assessed using any bag system
Continuous airway pressure case series have suggested that early or delivery room use of continuous positive airway pres-sure (CPAP) in premature babies may reduce chronic lung dis-ease There have been two randomized trials of which one was a pilot study The data from the COIN trial do not show any advan-tage other than a reduction in intubation and surfactant use in the intervention group However an excess of pneumothorax
8 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
was also reported The Vermont Oxford Network and the SUP-PORT trials will provide further data but at present the delivery room use of CPAP cannot be widely recommended and should be limited to those units experienced in its use or taking part in research
Air or oxygen oxygen has been in widespread use for resuscita-tion at birth since the 1930s and even hyperbaric oxygen was seriously supported in the 1960s For many years there have been concerns about tissue damage from oxygen deprivation during and after resuscitation It became evident in the 1950s that unrestricted oxygen therapy could have serious conse-quences for future vision More recently concerns have been raised about potential adverse effects on respiratory physiology cerebral circulation and tissue damage from oxygen free radicals even during resuscitation A meta-analysis of four human studies demonstrated a reduction in mortality and no evidence of harm in infants resuscitated in air versus 100 oxygen3233 However there are several significant methodological concerns with these studies and the results should be interpreted with caution There is insufficient evidence to recommend any specific concentration of oxygen to be used for newborn resuscitation Monitoring the oxygen saturation of babies may be helpful but as yet there are no time-related normal target ranges and healthy term babies may take up to 10 min to achieve preductal oxygen saturation of greater than 95 and up to 60 min to achieve this postductally
There is therefore equipoise which would be open to an appropriate randomized controlled trial In the meantime the evidence only supports use of either 21 or 100 oxygen It is provoking to realize that if air had been in constant use since the 1930s there would be insufficient evidence for use of supple-mental oxygen
Circulation
Early resuscitation (temperature control airway breathing) provides oxygenated blood in the pulmonary arterioles which if returned to the heart causes the rate to increase34 If due to acidosis and hypoxia the circulation is ineffective then chest compressions may be needed They should be commenced when the heart rate remains below 60min despite effective airway and breathing management127 The best technique is using two hands to encircle the chest1 A ratio of three compressions to one breath is internationally accepted127 but has no evidence to support it Research has shown that neither compressions nor drugs will work in this situation without oxygenated blood so effective lung aeration and ventilation is essential A logical approach would be to fill the alveoli with air and to compress the chest until they are empty However training and teamwork require an agreed ratio which has therefore not changed since guidelines were first agreed internationally Success is assessed by an increase in heart rate which should therefore be assessed every 30 s Compressions stop when the spontaneous heart rate is greater than 60 beatsmin
In hypoxic newborn animal models successful resuscitation can restore cardiac output and blood pressure to levels above baseline within 5ndash10 min However it should be noted that there is a decline to 30 lower than basal levels within 2 h and that blood pressure is relatively spared suggesting an even greater
paeDiatRiCS anD CHilD HealtH 184 16
reduction in tissue perfusion This should be considered in the later care of any neonate who was hypoxic at birth
Drugs
Neonatal bradycardia at birth is almost always due to hypoxia plusmn acidosis and therefore drugs are rarely needed Adrenaline (epi-nephrine) is reported as being used in between 1 and 4 babies per 2000 births which is a large variation in practice Reported success is also variable and must be interpreted in light of this variation The use of drugs in extremely premature infants is con-troversial Some data suggested good outcomes for babies below 28 weeksrsquo gestation given adrenaline but these were flawed by high numbers of babies receiving resuscitative drugs some before the airway had been appropriately managed Audit data now suggest a poor outcome such that many clinicians would now council against the use of adrenaline and other drugs to resuscitate extremely premature newborn babies
Adrenaline (epinephrine)In 2003 a Cochrane review of randomized controlled trials involv-ing adrenaline use for resuscitation of neonates was unable to identify a single clinical trial35 Despite the lack of human neo-natal data animal models show the potential of adrenaline in asphyxial cardiac arrest and it is reasonable to use it when ade-quate ventilation and chest compressions have failed to increase the heart rate above 60 beatsmin Use 10ndash30 μgkg intrave-nously and preferably via an umbilical venous line The tracheal route cannot be recommended but if used it is likely that doses within this range will be ineffective and 100 μgkg might be tried However the safety of such doses has not been studied
BicarbonateThe use of bicarbonate has long been controversial but many of the concerns relate to the rapid correction of acidosis in neonates after resuscitation or the routine use of bicarbonate infusion nei-ther of which can be advocated There are no published human neonatal data to support its use although some exist from animal studies Animal data have also shown that the binding of adren-aline to receptors in the myocardium is significantly impaired by lactic acidosis and recent work on human lymphocyte beta-adrenergic receptors supports this view Whether this is also true of the more important alpha receptors is unknown In practice reversing intracardiac acidosis may improve myocardial function and assist in achieving a return of spontaneous circulation 1ndash2 mmolkg of bicarbonate may be given but this remains a contro-versial area
VolumeVolume expansion should only be given when it is suspected that the baby has suffered blood loss or the infant appears to be in shock (pale poor perfusion weak pulse) and has not responded adequately to other resuscitative measures If there is no history suggestive of blood loss shock is most likely to be due to myo-cardial dysfunction in which case fluids should be administered cautiously The most logical replacement fluid would be blood but in its absence isotonic crystalloid rather than albumin is the solution of choice given in 10 mlkg aliquots and observing the response Three randomized trials in neonates have shown
9 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
isotonic crystalloid to be as effective as albumin for the treat-ment of hypotension but none has examined either the relative or actual effectiveness in resuscitation A recent blinded randomized study comparing normal saline albumin or no volume expansion in a normovolaemic asphyxiated neonatal animal model showed that volume expansion was not beneficial and made a number of parameters worse36
NaloxoneNaloxone is not recommended as part of the initial resuscita-tion of newborns with respiratory depression Before it is given supporting ventilation should have restored the heart rate and colour The dose is 100 μgkg intravenously or intramuscularly Tracheal administration cannot be recommended Although administration of naloxone to neonates who have been exposed to maternal opioids during labour is a practice of long-standing it lacks the proper evidence of efficacy
Non-response to resuscitation
There are few more frightening situations professionally than applying the correct interventions in resuscitating or stabilizing a baby and getting no response Each stage must be adequately performed before moving onto the next and this requires regular reassessment When experienced help is needed at a newborn resuscitation it is usually the airway and ventilation that require correction If the heart rate does not increase this usually means that the lungs have not been successfully aerated In some cases however it may mean that the heart cannot respond as the cir-culation is inadequate In this situation the only way to check that the lungs have been successfully aerated is to see the chest move with ventilation or to obtain evidence of ventilation from a detector of exhaled carbon dioxide If you do not see chest movement after another five breaths the most likely cause is an obstructed airway either due to incorrect positioning or because the jaw has not been drawn forwards An oropharyngeal airway can be very helpful at this point especially in the term baby Only very occasionally is the airway blocked by mucus vernix blood or meconium but if the airway is guaranteed and there is no heart rate response or chest movement this should be sought by direct suction of the trachea even in the absence of any meconium staining of liquor Pneumothoraces can occur spontaneously after delivery but are rare at resuscitation carried out with pressure-limited devices Equally rare are diaphragmatic hernias that have not been diagnosed antenatally giving problems at resuscitation
If the chest is moving but the heart rate has not responded to resuscitation consider rare possibilities such as fetal blood loss pneumothorax or heart block (mothers with undiagnosed systemic lupus erythematosis delivered for fetal bradycardia) as possibilities With adequate ventilation there is no evidence of oxygen concentrations less than 100 being responsible for prolonged bradycardia or failure to respond although current practice would support increasing the delivered oxygen concen-tration if resuscitation had been commenced using air
Outcome
The prognosis for the full-term baby subjected to sudden acute asphyxia is usually good provided the episode does not last for
paeDiatRiCS anD CHilD HealtH 184 17
long Most babies resuscitated from primary apnoea have no sequelae secondary to the resuscitation Many babies who start to breathe again regularly within 20 min of the circulation being restored recover completely but it is rare for a baby who is still gasping after 30 min to recover
The prognosis for the preterm baby of less than about 34 weeksrsquo gestation subjected to severe acute anoxia is less predict-able This is because of the risk of secondary intraventricular haemorrhage or periventricular intracerebral haemorrhage andor infarction after even a relatively brief asphyxial episode espe-cially in the period immediately around birth
The effects of chronic hypoxia are also difficult to predict but a reasonably clear idea of the extent of the problem should be obtainable within 36ndash48 h of the original chronic asphyxial insult A mild short-lasting state of hyperexcitability usually car-ries a good prognosis even if there is seizure activity but more severe symptoms can be associated with permanent handicap This is seen especially in infants with encephalopathy requiring ventilation
REFERENCEs
1 Biarent D Bingham R Richmond S et al european Resuscitation
Council guidelines for Resuscitation 2005 Section 6 paediatric life
support Resuscitation 2005 67(suppl 1) S97ndashS133
2 international liaison Committee on Resuscitation part 7 neonatal
resuscitation Resuscitation 2005 67 293ndash303
3 Singh J Santosh S Wyllie J mellon a effects of a course in
neonatal resuscitation - evaluation of an educational intervention
on the standard of neonatal resuscitation Resuscitation 2006 68
385ndash389
4 palme-Kilander C methods of resuscitation in low-apgar-score
newborn infants - a national survey Acta Paediatr 1992 81
739ndash744
5 Kroll l twohey l Daubeney p et al Risk factors at delivery and
the need for skilled resuscitation Eur J Obstet Gynecol Reprod Biol
1994 44 175ndash177
6 Wyllie Jp Resuscitation of the newborn The Foundation Years
2007 3(4) 153ndash157
7 Richmond S ed newborn life Support Resuscitation at Birth
london Resuscitation Council 2006
8 Ceriani Cernadas Jm Carroli g pelligrine l et al the effect of timing
of cord clamping on neonatal venous hematocrit values and clinical
outcome at term a randomized controlled trial Pediatrics 2006
117 e779ndashe786
9 mercer JS Vohr BR mcgrath mm padbury JF Wallach m oh W
Delayed cord clamping in very preterm infants reduces the incidence
of intraventricular hemorrhage and late-onset sepsis a randomized
controlled trial Pediatrics 2006 117 1235ndash1242
10 Dahm lS James lS newborn temperature and calculated heat loss
in the delivery room Pediatrics 1972 49 504ndash513
11 Stephenson J Du J tk o the effect of cooling on blood gas
tensions in newborn infants J Pediatr 1970 76 848ndash852
12 gandy gm adamsons Jr K Cunningham n Silverman Wa James lS
thermal environment and acid-base homeostasis in human infants
during the first few hours of life J Clin Invest 1964 43 751ndash758
13 gluck l Kulovich mV eidelman ai et al Biochemical development
of surface activity in mammalian lung pulmonary lecithin synthesis
0 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
in the human fetus and newborn and etiology of the respiratory
distress syndrome Pediatr Res 1972 6 81ndash99
14 Vohra S Roberts RS Zhang B Janes m Schmidt B Heat loss
prevention (Help) in the delivery room a randomised controlled
trial of polyethylene occlusive skin wrapping in very preterm infants
J Pediatr 2004 145 750ndash753
15 owen CJ Wyllie Jp Determination of heart rate in babies at birth
Resuscitation 2004 60 213ndash217
16 orsquoDonnell Cp Kamlin Co Davis pg Carlin JB morley CJ Clinical
assessment of infant colour at delivery Arch Dis Child Fetal
Neonatal Ed 2007 92 F465ndashF467
17 international liaison Committee on Resuscitation part 13 neonatal
Resuscitation guidelines Circulation 2005 112(suppl 24)
iV188ndashiV195
18 leone ta Rich W Finer nn neonatal intubation Success of
pediatric trainees J Pediatr 2005 146 638ndash641
19 orsquoDonnell Cp Kamlin Co Davis pg morley CJ endotracheal
intubation attempts during neonatal resuscitation success
rates duration and adverse effects Pediatrics 2006 117
e16ndash21
20 Repetto Je Donohue pa-CpK Baker SF Kelly l nogee lm use of
capnography in the delivery room for assessment of endotracheal
tube placement J Perinatol 2001 21 284ndash287
21 gandini D Brimacombe JR neonatal resuscitation with laryngeal
mask airway in normal and low birth weight infants Anesth Analg
1999 89 642ndash643
22 esmail n Saleh m ali a laryngeal mask airway versus endotracheal
intubation for apgar score improvement in neonatal resuscitation
Egypt J Anesthiol 2002 18 115ndash121
23 Wiswell te gannon Cm Jacob J et al Delivery room management
of the apparently vigorous meconium-stained neonate results of
the multicenter international collaborative trial Pediatrics 2000
105 1ndash7
24 Vain ne Szyld eg prudent lm Wisewell te aguilar am Vivas ni
oropharyngeal and nasopharyngeal suctioning of meconium-stained
neonates before delivery of their shoulders multicentre randomised
controlled trial Lancet 2004 364 597ndash602
25 Bjorklund lJ ingimarsson J Curstedt t larsson a Robertson B
Werner o lung recruitment at birth does not improve lung function
in immature lambs receiving surfactant Acta Anaes Scand 2001 45
986ndash993
26 Bjorklund lJ ingimarsson J Curstedt t et al manual ventilation
with a few large breaths at birth compromises the therapeutic effect
of subsequent surfactant replacement in immature lambs Pediatr
Res 1997 42 348ndash355
paeDiatRiCS anD CHilD HealtH 184 17
27 taskar V John J evander e Robertson B Jonson B Surfactant
dysfunction makes lungs vulnerable to repetitive collapse and re-
expansion Am J Respir Crit Care Med 1997 155 313ndash320
28 muscedere Jg mullen JB gan K Slutsky aS tidal ventilation at low
airway pressures can augment lung injury Am J Respir Crit Care Med
1994 149 1327ndash1334
29 nilsson R grossman g Robertson B Bronchiolar epithelial lesions
induced in the premature rabbit neonate by short periods of artificial
ventilation Acta Pathol Microbiol Scand 1980 88 359ndash367
30 probyn me Hooper SB Dargaville pa et al positive end expiratory
pressure during resuscitation of premature lambs rapidly improves
blood gases without adversely affecting arterial pressure Pediatr
Res 2004 56 198ndash204
31 Wood Fe morley CJ Dawson Ja et al improved techniques
reduce face mask leak during simulated neonatal resuscitation
study 2 Arch Dis Child Fetal Neonatal Ed in press doi101136
adc2007117788
32 tan a Schulz a orsquoDonnell CpF Davis pg air versus oxygen for
resuscitation of infants at birth Cochrane Database Syst Rev 2004
(3) CD002273
33 Davis pg tan a orsquoDonnell Cp Schulze a Resuscitation of newborn
infants with 100 oxygen or air a systematic review and meta-
analysis Lancet 2004 364 1329ndash1333
34 Dawes g Fetal and neonatal physiology Chicago year Book
publisher 1968 p 141ndash159
35 Ziino aJa Davies mW Davis pg epinephrine for the resuscitation
of apparently stillborn or extremely bradycardic newborn infants
Cochrane Database Syst Rev 2003 (2) CD003849
36 Wyckoff m garcia D margraf l perlman J laptook a Randomized
trial of volume infusion during resuscitation of asphyxiated neonatal
piglets Pediatr Res 2007 61 415ndash420
Practice points
bull Resuscitation at birth is different from that at all other times
of life
bull a standard approach can be applied to most newborn
resuscitation
bull guidelines are based on a rigorous evaluation of evidence
where possible
bull evidence is sparse but evolving
bull most preterm babies require stabilization rather than
resuscitation
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Acidndashbase physiology and blood gas interpretation in the neonateSusern tan
morag Campbell
Abstractacidndashbase balance describes the complex processes that work to main-
tain a stable extracellular pH for optimal cellular function the process
of balancing the production and neutralization of tissue acid provides a
great challenge for newborn infants who have significantly higher rates
of acid production than adults Factors which help maintain a stable
acidndashbase balance include buffers the respiratory system and renal sys-
tem Both intracellular and extracellular buffers resist changes in pH
the most important extracellular buffer system for maintaining stable
pH is the bicarbonate system in response to acidosis or alkalosis the
respiratory system balances the production of acid with the clearance
of Co2 by altering respiratory rate the kidneys provide a delayed but
sustained response to pH imbalance by excreting either acidic or alkaline
urine in response to systemic acidosis and alkalosis respectively in sick
premature infants these systems have a limited capacity completely to
control pH this review discusses the physiology of the three systems
which control acidndashbase balance patterns of clinical abnormalities in
acidndashbase status and their underlying causes are discussed We present
a systematic approach to blood gas analysis and interpretation in new-
born infants
Keywords acidosis alkalosis bicarbonate bloodndashgas analysis
metabolic pH
Introduction
Blood gas analysis is a routine procedure performed on newborn babies receiving respiratory support in the neonatal intensive care The combination of invasive and non-invasive assessment of ventilation and oxygenation enables clinicians appropriately to modify respiratory care according to each individual babyrsquos rapidly changing clinical status
Understanding the fundamentals of acidndashbase balance helps us to use blood gas analysis not only to assess respiratory sta-tus but also to provide information on metabolic status and the adequacy of tissue perfusion
Susern Tan MBBS MRCP is Clinical Fellow at the Neonatal Intensive Care
Unit 6th Floor North Wing St Thomasrsquo Hospital London SE1 7EH UK
Morag Campbell MBChB MRCP is Consultant Neonatologist at the
Neonatal Intensive Care Unit 6th Floor North Wing St Thomasrsquo
Hospital London SE1 7EH UK
paeDiatRiCS anD CHilD HealtH 184 17
What is understood by acid-base balance
Acidndashbase balance refers to the complex physiological processes used by the body to maintain a stable extracellular pH1 A serum pH within the range of 735ndash745 provides the ideal environment for cellular metabolism Maintaining a stable pH is critical as the metabolic activity of proteins is pH dependent and small changes in hydrogen ion (H+) concentration can potentially alter physio-logical function
Acids are substances that yield free H+ in solution while a base accepts H+ and in solution combines with an acid to neu-tralize it In the normal metabolic state H+ are continuously pro-duced and neutralized to maintain a steady pH balance12 The rate of H+ production is two to three times higher in neonates because of their rapid growth rates and increased acid production from protein turnover and bone mineralization The challenge of maintaining a stable pH through processing and neutralizing H+ is therefore greatest in newborn infants
Using exact values of H+ concentration to assess acidndashbase status is cumbersome and it is more commonly expressed as pH defined by the equation
pH = minuslog H+
Maintaining acidndashbase balance
The balance between production and excretion of acids in the body is controlled by buffer systems which have an immediate effect and by the respiratory and the renal systems
Buffer systemsBuffer solutions resist change in pH when acid or alkali is added due to their capacity to absorb or give up H+ The three main buffer systems in the body are the bicarbonate phosphate and protein systems1ndash3 The protein and phosphate buffer systems are intracellular and act as lsquosinksrsquo for extracellular H+ which are exchanged with intracellular potassium (K+) and sodium ions (Na+) In an acute metabolic acidosis hyperkalaemia may develop due to this H+ exchange4
The bicarbonate buffer system is extracellular and consists of a mixture of carbonic acid (H2CO3) and sodium bicarbon-ate (NaHCO3) This buffer system helps maintain a stable pH by soaking up excess H+ with HCO3
minus which in solution forms carbonic acid (H2CO3) Carbonic acid is a weak acid and readily dissociates to give CO2 which is transported in dissolved form to the lungs for excretion
H+ + HCO3minus harr H2CO3 harr H2O + CO2
The bicarbonate system therefore completes the neutraliza-tion of excess H+ and a stable plasma pH is maintained The relationships between pH HCO3
minus and CO2 in this system are described by the HendersonndashHasselbalch equation15
pH = 61 + log HCO3minus003 times CO2
where 61 is the log of the dissociation coefficient of carbonic acid and 003 the solubility of CO2 in plasma Buffers are most potent when there are equal amounts of H+ and HCO3
minus in solution The
2 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
bicarbonate system is not a potent buffer however as HCO3minus
and CO2 are readily altered by the body this system plays a very powerful role in pH homeostasis15
Respiratory regulationThe respiratory system adapts within minutes to hours as part of the acute response to acidosis This system modifies pH by balancing production of H+ with ventilatory clearance of CO2
H+ directly stimulates chemoreceptors in the respiratory cen-tre of the brainstem producing an increase in respiratory rate26 The response to respiratory acidosis is very rapid as CO2 easily diffuses across the bloodndashbrain barrier however in metabolic acidosis compensation is delayed until plasma bicarbonate fully equilibrates with cerebrospinal fluid (CSF) bicarbonate There is an inverse relationship between alveolar ventilation and partial pressure of dissolved carbon dioxide (PaCO2) a reduction in alveolar ventilation raises PaCO2 and decreases pH Changes in pH therefore affect alveolar ventilation and conversely changes in alveolar ventilation cause significant changes in pH
Renal regulationThe kidneys provide a delayed but sustained response to acidndashbase imbalances by excreting either acidic or alkaline urine In full-term and preterm babies the capacity for acid excretion and bicarbonate reabsorption is reduced as glomerular filtration rates are low and tubular function immature7 Renal function matures with gestation postnatal age and glucocorticoid and thyroid hormones78 Due to their limited capacity to preserve HCO3
minus newborn infants have lower serum bicarbonate levels and are predisposed to acidosis7
Bicarbonate is not effectively reabsorbed due to its size and electrical charge Instead intraluminal HCO3
minus combines with secreted H+ in tubular luminal fluid to produce carbonic acid which dissociates to give H2O and CO2 This CO2 diffuses into tubular cells combines with intracellular H2O and forms carbonic acid which liberates HCO3
minus and H+ HCO3minus is then
recovered to the circulation by exchange for chloride ions (Clminus) through the basal cell membrane247
Renal acid secretion occurs at all sites except the loop of Henle Primary active transport accounts for 5 and secondary for the remaining 95 of total H+ excretion Secondary trans-port involves an exchange between luminal Na+ and intracel-lular H+ Both ions bind to a membrane transport protein The Na+ concentration gradient between the tubular lumen and cells enables Na+ drag into the cell which generates energy to fuel active H+ excretion into the tubular lumen1ndash47
Quantifying acidosis
Standard base excess is a calculated value derived from PaCO2 and pH It is expressed as the mmollitre of base above or below normal buffer bases required to correct the pH to 74 at a PaCO2 of 40 mmHg A negative base excess or base deficit indicates an acidosis while a positive base excess indicates a relative alkalosis15
Anion gap is the measured difference between anions and cations in the blood
Anion gap = (Na+ + k+) minus (HCO3+Clminus)
paeDiatRiCS anD CHilD HealtH 184 17
Calculation of the anion gap enables clinicians better to define the underlying cause of a metabolic acidosis9 The common causes of an increased anion gap acidosis in neonates include lactic acidosis due to tissue hypoperfusion and hypoxia it may also be seen with certain inborn errors of metabolism and in uraemia910 The anion gap can help distinguish between the rela-tively benign non-anion gap hyperchloraemic acidosis seen in premature infants and a pathological lactic acidosis due to poor end-organ perfusion1011
Strong ion theory
Stewart described a complex acidndashbase model which proposed that H+ concentration results from the dissociation of water which is influenced by PaCO2 the strong ion difference and plasma weak acids12
Strong ions are ions that dissociate at normal body pH and include Na+ K+ and Clminus Weak acids in plasma which contrib-ute include albumin inorganic phosphate and plasma proteins their concentrations do not change with pH and are therefore a constant The effect of these factors and other unmeasured tissue ions on acidndashbase status can be quantified by the calculation of the strong ion gap (SIG)112 In the neonatal unit it is perhaps more important that we consider how principles of this model may relate to acidndashbase status rather than fully to quantify the SIG Theoretically low albumin and phosphate levels which fre-quently occur in premature infants by reducing the concentra-tion of weak acids can produce a relative alkalosis while high phosphate levels in renal failure may contribute to acidosis
Tissue oxygenation
Oxygenation is closely linked to acidndashbase status as optimal cel-lular function requires oxygen to fuel aerobic metabolism and produce energy In hypoxic conditions anaerobic metabolism predominates which is energy inefficient and results in a lactic acidosis1011
Tissue oxygen availability is related to regional blood flow haemoglobin level and haemoglobin oxygen affinity Arterial blood gases measure the partial pressure of dissolved oxygen (PaO2) which represents a small component of total oxygen con-tent the majority being transported bound to haemoglobin The relationship between percentage haemoglobin saturation (SaO2) and PaO2 is described by the sigmoidal oxyhaemoglobin disso-ciation curve which enables us to relate the two measures to each other235 The affinity of haemoglobin for oxygen is altered by local tissue factors Increases in temperature H+ PaCO2 and 23-diphosphoglycerate (DPG) levels shift the oxyhaemoglobin dissociation curve to the right reducing affinity for oxygen Decreases in temperature H+ PaCO2 and 23-DPG levels shift the curve to the left increasing oxygen affinity1ndash35 In the body haemoglobin oxygen affinity continuously changes increasing in the lungs to enable efficient oxygen uptake and decreasing at tissue level to provide efficient oxygen delivery to metabolically active tissues
Avoiding both hypoxia and hyperoxia is important in the neo-natal unit as deleterious effects of hypoxia are seen in infants with pulmonary hypertension1314 while hyperoxia is associated with an increased incidence of retinopathy of prematurity1516
3 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Clinical acidndashbase imbalances
Clinical acidndashbase imbalances can be respiratory metabolic or a mixture of both These abnormalities may be corrected by the acidndashbase regulatory mechanisms in the body in an attempt to maintain normal pH (Figure 1)
Respiratory acidosisThis occurs when any disorder leads to decreased alveolar ventilation Common causes of respiratory acidosis are listed in Table 1 Reduced respiratory clearance of CO2 means more dissolved CO2 accumulates in the plasma leading to increased production of carbonic acid and H+ Through chemoreceptor stimulation respiratory acidosis rapidly alters ventilation in an attempt to reduce CO226 Chemoreceptor mediated ventila-tory increases may only partly adjust in premature infants with underlying lung disease In babies with a sustained respiratory acidosis eg in chronic lung disease then metabolic compen-sation occurs through increased renal excretion of H+ and reabsorption of HCO3
minus slowly restoring pH to around 80 of normal47
paeDiatRiCS anD CHilD HealtH 184 17
The management of PaCO2 levels in infants receiving mechan-ical ventilation has important clinical implications Premature babies have impaired cerebral autoregulation17 and adverse neurological sequelae are reported in association with high PaCO2 levels18ndash20 Ventilation strategies which advocate lsquoper-missive hypercarbiarsquo have been developed to minimize airways damage from mechanical ventilation21 Published data suggest pulmonary benefits however the safe level of PaCO2 remains to be defined in premature infants2021
Respiratory alkalosisThis occurs when more CO2 is excreted than is produced by the body Pathological conditions leading to respiratory alkalosis are rare Hyperventilation in the neonatal setting is often iatrogenic or may be due to disorders in brainstem control of breathing including hypoxicndashischaemic encephalopathy or primary central nervous system abnormalities (see Table 1)
If respiratory alkalosis is sustained it may be compensated for by reduced reabsorption of filtered bicarbonate Reported adverse associations of low PaCO2 include periventricular leuco-malacia and intraventricular haemorrhage1922
K+
H+
Overventilation
CO2 + H2O harr H2CO3 harr H+ + HCO3ndash
Bicarbonate Buffer
Intracellular Buffer
uarr H+ excretionuarr HCO3
ndash absorption
uarr buffered H+
(NH4+ H2PO4
ndash)uarr ventilation rate
RespiratoryAcidosis
MetabolicAcidosis
darr CO2and uarr pH
RespiratoryAlkalosis
MetabolicAlkalosis
darr H+ anduarr pH
darr ventilation rate
uarrCO2
and darr pH
darr H+ excretiondarr HCO3
ndash absorption
uarrH+ and
darr pH
Brain
Brain
Intracellular Buffer
H+
K+
Sepsis
HypoxiaRDS
Metabolismand growth
Diuretics
Airwayobstruction
Neuromuscularproblems
IEM
Gastric losses
+ +
ndash -
Renal BufferRespiratory Buffer
Figure 1 mechanisms for regulation of extracellular pH iem inborn errors of metabolism RDS respiratory distress syndrome
4 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Common causes of acidndashbase imbalances
pH PCO2 H2CO3 Base excess Common neonatal causes
Respiratory acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
uarr normal normal bull upper airway obstruction choanal atresia
pierre-Robin sequence
bull lung abnormalities respiratory distress
syndrome transient tachypneoa of
newborn pneumonia meconium aspiration
syndrome pulmonary hypoplasia
congenital pulmonary malformations
bull Central hypoventilation hypoxic-ischaemic
encephalopathy intracranial haemorrhage
bull neuromuscular insufficiency congenital
myopathies congenital neuropathies
bull iatrogenic inadequate ventilatory settings
Compensated lower limit
of normal
uarr uarr gt+3
metabolic acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
normal darr ltminus3 increased anion gap
bull lactic acidosis sepsis hypoperfusion
shock necrotizing enterocolitis
bull inorganic acidosis inborn errors of
metabolism renal failure
normal anion gap
bull increased gastrointestinal H2Co3 losses
ileostomy diarrhoea
bull Renal tubular acidoses
Compensated lower limit
of normal
darr darr ltminus3
Respiratory alkalosis Uncompensated gt 745 darr normal normal bull iatrogenic excessive ventilatory settings
bull Compensatory hyperventilation hypoxic-
ischaemic encephalopathy
Compensated higher limit
of normal
darr darr ltminus3
metabolic alkalosis Uncompensated gt 745 normal uarr gt+3 bull gastric losses vomiting non-replacement
of excessive nasogastric aspirates
bull thiazide and loop diuretics
bull Hypokalaemia
Compensated higher limit
of normal
uarr uarr gt+3
Table 1
Metabolic acidosisThis frequently affects infants in the neonatal unit and has many causes1011 (see Table 1) There may be overproduction of tissue acid impaired acid clearance gastrointestinal loss of bicarbonate or an exogenous increased acid load eg chloride total paren-teral nutrition (TPN) or albumin1ndash323
Calculation of the anion gap to distinguish an increased anion gap acidosis from a non-anion gap acidosis is important both for treatment and prognosis1011 Acidosis stimulates respiratory compensation but this is limited in unstable infants Similarly renal compensation with improved HCO3
minus conservation is con-strained by tubular immaturity Treatment of the acidosis should be directed at the underlying cause eg hypoxia hypotension or excess Clminus rather than by administration of base
Metabolic alkalosisThis is unusual in neonates and is most frequently seen in infants with chronic lung disease or heart failure who are receiving diuretics Diuretics cause alkalosis by increasing renal fluid and Na+ losses An active process to reabsorb Na+ occurs in tubule cells which through enhanced H+ secretion and HCO3
minus reab-sorption produce alkalosis27
paeDiatRiCS anD CHilD HealtH 184 17
Metabolic alkalosis may also occur with excessive loss of gas-tric contents eg protracted vomiting or inadequate replacement of nasogastric aspirates (see Table 1)
Interpreting blood gases
Blood gas measurements can provide important diagnostic and prognostic information and a systematic approach to blood gas analysis is described in Table 2 The clinical management of infants with abnormal gases requires a good understanding of acidndashbase physiology and tissue oxygenation and an apprecia-tion of factors which may affect the reliability of samples
Arterial blood sampling is the gold standard however indwelling arterial catheters and arterial stab samples are usually restricted to infants who are critically ill or those who require sig-nificant ongoing intervention Gases are most frequently measured in capillary or venous samples which correlate well with arterial samples for PaCO2 pH and base excess in babies and children receiving intensive care These correlations however are not valid in infants with peripheral vasoconstriction and hypotension2324
Non-invasive monitoring techniques may enable us to reduce the frequency of blood gas sampling Transcutaneous monitoring
5 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
A systematic approach to blood gas analysis
1 Collect the relevant information
bull type of gas ndash capillary or arterial
bull Current respiratory support ndash document level
bull transcutaneous Co2 and Sao2 levels
bull Clarify no significant clinical events before sampling
2 pH accept a range between 730 and 745 in newborn
babies this is lower than in older children is there an
alkalosis (pH gt 745) or an acidosis (lt 730)
3 Co2 aim for a range between 45 and 65 kpa a paCo2 level
more than 65 kpa suggests inadequate alveolar ventilation
while less than 45 kpa suggests hyperventilation Correlate
values with non-invasive measures
4 o2 Can only be assessed from arterial gases aim for pao2
between 60 and 80 kpa Correlate results with pulse
oximetry levels
5 HCo3 and base excess normal HCo3 level is between 20 and
24 mmollitre and bases excess +3 to minus3
6 anion gap look at the anion gap and lactate to help identify
the cause of an acidosis normal lactate levels should be less
than 2 mmollitre
7 Respiratory or metabolic compensation look at the pH and
assess whether it is appropriate for the Co2 level or is there
evidence of compensation
8 interpret use both the clinical history and blood gas
findings to help you identify the primary problem aim your
management at treating the underlying cause
9 Reassess if clinical management changes have been made
repeat the blood gas after an appropriate time interval to
ensure improvement
Table 2
provides a highly accurate and reliable method for measuring PaCO2 through the skin it can however be technically difficult may cause tissue damage and is of limited reliability when peripheral perfusion is reduced25 Continuous end-tidal CO2 measurements correlate well with arterial CO2 values in patients with normal ventilation and perfusion however in babies with lung disease alveolar collapse small tidal volumes and rapid respiratory rates can make these measurements unreliable26 Despite its limitations transcutaneous monitoring provides the best method for CO2 trend monitoring in the neonatal intensive care unit (NICU)25
Oxygen saturation levels can be continuously measured non-invasively using pulse oximetry While oximetry is easy to perform and accurate on occasion SaO2 levels obtained may be unreliable when tissue perfusion is poor or with movement artefact SaO2 monitoring is highly sensitive at detecting hypoxia but is limited in detecting hyperoxia as at levels more than 90 small changes in SaO2 may result in unacceptably large increases in PaO227 It is therefore essential that SaO2 alarm limits are set for all neonates receiving respiratory support to detect hypoxia and prevent hyperoxia1627
Continuous non-invasive monitoring provides invaluable information when managing complex infants in the NICU but it does not replace the need for regular blood gas analysis
paeDiatRiCS anD CHilD HealtH 184 17
ReFeRenCeS
1 Kellum Ja Determinants of blood pH in health and disease
Crit Care 2000 4 6ndash14
2 Quigley R Baum m neonatal acid base balance and disturbances
Semin Perinatol 2004 28 97ndash102
3 Brouillette Rt Waxman DH evaluation of the newbornrsquos blood gas
status Clin Chem 1997 43 215ndash221
4 Chan JC acid-base disorders and the kidney Adv Pediatr 1983 30
401ndash471
5 Siggaard-andersen o the pH-log pCo2 blood acidndashbase nomogram
revised Scand J Lab Invest 1962 14 598ndash604
6 Saetta m mortola Jp interaction of hypoxic and hypercapnic stimuli
on breathing pattern in the newborn rat J Appl Physiol 1987 62
506ndash512
7 Baum m Quigley R postnatal renal development in Seldin DW
giebisch g eds the kidney physiology and pathophysiology new
york lippincott Williams and Wilkins 2000 p 703ndash726
8 ortiz la Quan a Weinberg a et al effect of prenatal
dexamethasone on rat renal development Kidney Int 2001 59
1663ndash1669
9 gabow pa Kaehny WD Fennessey pV goodman Si gross pa
Schrier RW Diagnostic importance of an increased serum anion gap
N Engl J Med 1980 303 854ndash858
10 lorenz Jm Kleinman li markarian K oliver m Fernandez J Serum
anion gap in the differential diagnosis of metabolic acidosis in
critically ill newborns J Pediatr 1999 135 751ndash755
11 Deshpande Sa platt mp association between blood lactate and
acid-base status and mortality in ventilated babies Arch Dis Child
1997 76 F15ndash20
12 Stewart pa modern quantitative acid-base chemistry Can J Physiol
Pharmacol 1983 61 1444ndash1461
13 Dakshinamurti S pathophysiologic mechanisms of persistent
pulmonary hypertension of the newborn Pediatr Pulmonol 2005
39 492ndash503
14 mourani pm ivy DD gao D abman SH pulmonary vascular
effects of inhaled nitric oxide and oxygen tension in
bronchopulmonary dysplasia Am J Respir Crit Care Med 2004
170 1006ndash1013
15 Deulofeut R Critz a adams-Chapman i Sola a avoiding hyperoxia
in infants le 1250 g is associated with improved short- and long-
term outcomes J Perinatol 2006 26 700ndash705
16 Chow lC Wright KW Sola a Can changes in clinical practice
decrease the incidence of severe retinopathy of prematurity in very
low birth weight infants Pediatrics 2003 111 339ndash345
17 Boylan gB young K panerai RB Rennie Jm evans DH Dynamic
cerebral autoregulation in sick newborn infants Pediatr Res 2000
48 12ndash17
18 Kaiser JR gauss CH pont mm Williams DK Hypercapnia during
the first 3 days of life is associated with severe intraventricular
hemorrhage in very low birth weight infants J Perinatol 2006 26
279ndash285
19 Fabres J Carlo Wa phillips V Howard g ambalavanan n Both
extremes of arterial carbon dioxide pressure and the magnitude of
fluctuations in arterial carbon dioxide pressure are associated with
severe intraventricular hemorrhage in preterm infants Pediatrics
2007 119 299ndash305
20 thome uH Carroll W Wu tJ et al outcome of extremely preterm
infants randomized at birth to different paCo2 targets during the
first seven days of life Biol Neonate 2006 90 218ndash225
6 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
21 Carlo Wa Stark aR Wright ll et al minimal ventilation to prevent
bronchopulmonary dysplasia in extremely-low-birth-weight infants
J Pediatr 2002 141 370ndash374
22 okumura a Hayakawa F Kato t et al Hypocarbia in preterm
infants with periventricular leukomalacia the relation between
hypocarbia and mechanical ventilation Pediatrics 2001 107
469ndash475
23 peters o Ryan S matthew l Cheng K lunn J Randomised
controlled trial of acetate in preterm neonates receiving parenteral
nutrition Arch Dis Child 1997 77 F12ndash15
24 yildizda D yapiciolu H yilmaz Hl Sertdemir y Correlation of
simultaneously obtained capillary venous and arterial blood gases
of patients in a paediatric intensive care unit Arch Dis Child 2004
89 176ndash180
25 aliwalas ll noble l nesbitt K et al agreement of carbon
dioxide levels measured by arterial transcutaneous and end tidal
methods in preterm infants 28 weeks gestation J Perinatol 2005
25 26ndash29
26 Hagerty JJ Kleinman me Zurakowski D et al accuracy of a new
low-flow sidestream capnography technology in newborns a pilot
study J Perinatol 2002 22 219ndash225
paeDiatRiCS anD CHilD HealtH 184 17
27 poets CF Wilken m Seidenberg J Southall Dp von der Hardt H
Reliability of a pulse oximeter in the detection of hyperoxemia
J Pediatr 1993 122 87ndash90
Practice points
bull a stable extracellular pH is important for optimal cellular
functioning
bull abnormalities in acidndashbase balance are regulated by buffer
systems and the respiratory and renal tract
bull maintaining a stable pH is challenging for newborn babies
due to their high rates of acid production and immature
regulatory mechanisms
bull arterial or capillary blood gases provide an effective way to
monitor acidndashbase balance in newborns
bull Blood gases should be analysed in a structured manner
assessing pH and then respiratory and metabolic components
bull the treatment of acidndashbase abnormalities should be directed
at the underlying problem not merely at correcting pH
7 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Recognition and management of neonatal seizuresmalcolm levene
AbstractSeizures are the most common major manifestation of central nervous
system dysfunction in the newborn there are many causes but perina-
tal asphyxia and haemorrhagicinfarction lesions account for about 75
there is now considerable evidence that frequent but short seizures in
the neonate affect subsequent neurodevelopmental outcome Studies
using eeg or modified continuous tracing of eeg activity (aeeg or CFm)
have shown that there is often electroconvulsive dissociation this re-
fers to poor correlation between electrical seizures and clinical seizures
Commonly used anticonvulsants appear to increase electroconvulsive
dissociation effective management of neonatal seizures has proved very
disappointing and less than 50 of seizures are abolished by first-line
anticonvulsant medication (phenobarbitone or phenytoin) Drugs such
as midazolam and lidocaine may further reduce seizures but require
more evaluation the challenge is to assess new and more effective anti-
convulsants which are themselves associated with little neurotoxicity
Keywords antiepileptic drugs eeg neonatal seizures neurodegeneration
Convulsions are the most common major neurological sign seen in newborn infants and their incidence estimated from large population studies is 26 per 1000 live births1 Premature infants are over four times more likely to have convulsions than full-term infants12 Neonatal status epilepticus (continuous seizure activity lasting 30 min or more) diagnosed clinically is rare and accounts for only 5 of infants with seizures1 although this is now recognized more frequently as the result of continuous EEG monitoring3
Neonatal convulsions are described as presenting in a num-ber of different ways and various seizure types can be seen in the same baby over a number of hours The frequencies of the various patterns of seizure activity are given in Table 1 In very premature babies and to a lesser extent in term infants minor movement abnormalities may be difficult to identify as subtle seizures These include lip smacking tongue thrusting mouth-ing pedalling type movements of the lower limbs or swimming movements of the arms Apnoea can be a common manifesta-tion of subtle seizures The signs can be protean and vary from baby to baby or even in the same baby Virtually any stereotypic
Malcolm Levene MD FMedSc FRCPCH FRCH is Professor and Head of
Department of Paediatrics and Child Health at University of Leeds Leeds
and Honorary Neonatologist at Leeds General Infirmary Leeds UK
paeDiatRiCS anD CHilD HealtH 184 178
movement may be a manifestation of a seizure disorder in the newborn
Aetiology
The more carefully the fitting baby is investigated the more likely it is that a cause for the seizures will be found A number of recent papers have described the aetiology of neonatal con-vulsions after extensive investigations14 Tekgul et al4 recently studied a consecutive group of full-term infants with evidence of neonatal convulsions (recognized both clinically and on EEG) and reported their outcome Table 2 summarizes these data as well as risk of moderate or severe disability for each causative factor Perinatal asphyxia is the commonest cause for convul-sions in term infants with haemorrhagic or ischaemic lesions also being common
Overall the prognosis for the group of term babies with con-vulsions was good 72 had a favourable outcome Where asphyxia (hypoxicndashischaemic insult) is the cause of neonatal convulsions the outcome is poor in 50 The prognosis for neonatal convulsions when they were due to arterial or cere-brovenous infarction or intracranial haemorrhage was generally good Individually inborn errors are a very rare cause of neo-natal convulsions but in view of the treatable nature of some of these it is essential that these be considered and investigated appropriately5
Patterns of seizure activity in the newborn
Movement pattern Frequency ()
Clonic 50
tonic 20
Subtle 10ndash35 depending on maturity
myoclonic 5
Table 1
Cause incidence and outcome of neonatal convulsions in term infants14
Aetiological factor Incidence () Poor outcome ()
asphyxia 38ndash40 50
Cerebral arteriovenous
infarction
20 0
intracranial haemorrhage 12ndash20 13
Congenital cerebral anomaly 5ndash10 100
Hypoglycaemiahypocalcaemia 3ndash19
infection 3ndash20
inborn error of metabolism 1
unknown cause 10ndash13 0
Refers to moderate and severe neurodevelopmental abnormalitynumbers too small to make meaningful predictions
Table 2
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Controversies in the clinical management of neonatal seizures
In recent years we have learnt much more about the neurobi-ology of seizures and their effect on the developing brain The neonatal brain is in a neurophysiologically hyperexcitable state compared to the more mature brain and therefore is more prone to seizure activity This is due largely to a relative excess of GABA neuroreceptors GABA receptors are usually inhibitory but in the immature brain they have a paradoxically excitatory effect This changes at about term in primates and with progressive develop-ment they adopt a neuroinhibitory role6
The propensity to seizures in the neonatal brain makes resolv-ing the balance of risks between continuing seizure activity on the one hand against potentially adverse effects of therapy on the other a very important equation Added to this is the problem of accurately diagnosing neonatal seizures and whether commonly used anticonvulsants are successful in controlling them
These conundrums can be posed as a series of challenging questions which are discussed below
Do neonatal convulsions cause brain injuryConvulsions are a sign of neurological compromise and may indi-cate significant underlying structural brain damage or biochemi-cal disturbance which may cause further brain damage in its own right There has been considerable debate about the scale of the disability that convulsions cause the immature brain over and above that due to the underlying cause Most of our knowledge comes from studies in rodents and these have provided some tentative answers to this question
Seizures in the mature brain lead to neuronal necrosis but studies in very young rat pups whose brain development is somewhat similar to full-term infants have shown that a series of five brief seizures on five successive days does not cause struc-tural neuronal damage but does produce morphological changes in hippocampal neurones and worryingly deficits in the rat learning and visual spatial memory function in adolescent and adult life7 A single prolonged neonatal convulsion in similarly immature rats does not produce any functional effects8 Others have shown that following priming of the neonatal rat brain by short seizures as described above a further insult comprising induction of status epilepticus in the same rats at an older age causes neuronal necrosis9 This has been referred to as the lsquotwo hit hypothesisrsquo10
A more specific question is does seizure activity in an already significantly compromised brain cause additional neuropathol-ogy Wirrell et al11 studied a series of immature rat pups with the induction of an hypoxicndashischaemic (asphyxial) insult fol-lowed by either chemically-induced fits or a control sham pro-cedure In the more severely asphyxiated animals the degree of brain damage was increased significantly in those that had the additional burden of induced seizures
In summary these studies show that the immature brain is more resistant to short frequent post-seizure damage than the mature brain but despite resulting in no loss of neuronal numbers the function of the brain is permanently affected in later life In the asphyxiated brain seizures appear to have an additional adverse effect on brain damage Furthermore the immature brain that has been lsquoprimedrsquo by early seizures is more
paeDiatRiCS anD CHilD HealtH 184 179
vulnerable to status epilepticus later in life It would appear from these data that frequent seizures in the human infant should be stopped and this begs the question as to whether currently used anticonvulsants effectively control neonatal seizures
Can we rely on clinical versus EEG diagnosis of neonatal convulsionsTraditionally the diagnosis of neonatal convulsions has been made by observation and description of the frequency of abnor-mal movements EEG has been technically difficult in the hostile electrical activity of a neonatal intensive care environment and considerable expertise is required for analysis of the trace It is usually not practical to undertake traditional EEG recordings at the time the baby shows abnormal movements More recently various technological developments have allowed more direct investigation of neuronal electrical activity by either video-EEG or compressed recording of the amplitude integrated EEG (aEEG or CFM)
Rennie et al3 at Kingrsquos College Hospital London have under-taken extensive evaluation of video-EEG and have found that this technique detects many convulsions not recognized by a single channel aEEG or CFM trace Of 19 infants with evidence of convulsions on EEG only four were recognized on CFM but this may have been due to the observersrsquo lack of experi-ence with this technique In other centres that have developed appropriate expertise aEEG or CFM has proved more sensitive to the detection of seizures Video-EEG studies have also shown that many movements interpreted by experienced clinicians to be seizures are not associated with abnormal cortical activity Conversely many electrical seizures are not associated with abnormal movements This is referred to as electroconvulsive dissociation
In summary clinical observation alone to detect the fitting baby is unreliable in that it may either over-detect seizure activ-ity which is not present on EEG or under-detect clinical seizures in infants with EEG-proven convulsions The decision as to which babies to treat with antiepileptic drugs therefore becomes somewhat arbitrary
Do anticonvulsants stop neonatal seizuresAlthough neonatal seizures are common there are few random-ized controlled trials assessing the benefits of antiepileptic drugs (AEDs) in the treatment of this condition Phenobarbitone is the most widely used first-line AED and in an Australasian study 95 of neonatologists and paediatric neurologists used this drug as first-line management12 The most commonly used loading dosage is 20 mgkg but regimens of up to 40 mgkg have been recommended (Table 3)13 Four trials have evaluated the effect of phenobarbitone in abolishing neonatal seizures Two of these studies used EEG to monitor response to the drug1415 and one compared phenobarbitone with phenytoin15 In the latter study seizures were completely controlled in only 43 of babies and in the group where phenytoin was the first drug used com-plete seizure control was achieved in 45 This study switched babies from their first AED to the other if complete control was not obtained on EEG monitoring after exposure to first-line therapy In babies who had been given phenobarbitone as first-line therapy seizure control was only achieved in 57 after phenytoin was added In those given phenytoin first complete
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Dosage regimens for first- second- and third-line anticonvulsants in the neonatal period
Loading dose Second loading dose if first
unsuccessfulMaintenance dose
phenobarbitone 20 mgkg by slow iv injection 10 mgkg iv 25ndash5 mgkg od
phenytoin 20 mgkg iv over 20 min not recommended
midazolam 150ndash200 μgkg iv infusion 1 μgkgmin iv infusion increasing to 5 μgkgmin
until favourable response
lidocaine 2 mgkg iv over 10 min 6 mgkgh for 6 h iv then 4 mgkgh for 12 h then
2 mgkgh for 12 h
lorazepam 005ndash01 mgkg by slow iv injection
Diazepam 03ndash04 mgkg iv over 3ndash5 min
lidocaine should not be used if the infant has previously been treated with phenytoin
Table 3
seizure control was achieved with the adding of phenobarbitone in 62
Boylan et al14 assessed the efficacy of phenobarbitone (20ndash40 mgkg iv over 20 min) in 14 babies monitored by video-EEG in only four was there complete abolition of seizures and in the other 10 electroconvulsive seizure activity increased whereas clinical evidence of seizures reduced This has been termed elec-troclinical dissociation and anticonvulsant drug use in the new-born appears to increase this feature They also showed that the babies least likely to respond to the first-line AED are those with the most abnormal background EEG
Two studies have evaluated the use of phenobarbitone in babies who had sustained significant asphyxial insult at birth Hall et al13 compared high-dose phenobarbitone (mean 39 mgkg) versus standard dose (27 mgkg) and reported fewer convul-sions and a significant reduction of severe disability or death in the high dose group (RR 030 CI 010ndash093) A recent study from India16 of babies with hypoxicndashischaemic encephalopathy ran-domized 25 babies to phenobarbitone (20 mgkg loading dose) and compared them with 20 control babies Only 2 of 25 (4) in the phenobarbitone group developed convulsions compared with 8 of 20 (40) in the control group (p = 001) Because of the specific enrolment criteria (asphyxial insult) neither of these studies is strictly comparable to the studies by Painter et al15 and Boylan et al14 whose intention was to assess the efficacy of first-line anticonvulsant therapy on convulsions of any cause diagnosed either clinically or by EEG
Other anticonvulsants used as second- and third-line drugs have been subject to few studies in the newborn Midazolam is administered as a bolus followed by continuous infusion A recent study17 has shown that in 10 of 13 neonates given intravenous midazolam for status epilepticus control of electri-cal seizures was achieved within the first hour of treatment having been previously shown to be refractory to phenobarbi-tone treatment Some of these babies required a second bolus infusion of midazolam to obtain control of all electrographic seizures
In some parts of Europe lidocaine is used as a third-line anti-convulsant Malingre et al18 evaluated 20 infants refractory to
paeDiatRiCS anD CHilD HealtH 184 180
both phenobarbitone and midazolam and who were then given lidocaine by continuous infusion Lidocaine was effective in abolishing electroconvulsive seizures diagnosed by aEEG in 76 of the treatment courses studied No babies developed cardiac arrhythmias a previously reported complication of lidocaine in older patients As a result of pharmacokinetic studies the dosage regimen has been modified (see Table 3)
In summary phenobarbitone is effective in seizure control in less than 50 of babies and even when combined with phe-nytoin the efficacy of these drugs together remains poor More worrying is the observation that phenobarbitone tends to reduce clinically evident seizures thereby giving the clinician a false sense of security whilst having little or no effect on the num-bers of electroconvulsive disorders This has been summarized appropriately as lsquoafter all these years we still love what doesnrsquot workrsquo19 Both midazolam and lidocaine infusions appear to be effective in abolishing severe seizures in some infants resistant to phenobarbitone Lidocaine should not be given to babies previ-ously exposed to phenytoin for fear of a synergistic adverse effect on cardiac rhythm
Do antiepileptic drugs cause brain damageA riskndashbenefit analysis is needed to evaluate the efficacy of anticonvulsants in stopping neonatal seizures which is poor with standard anticonvulsants as discussed above against the risk of administering the anticonvulsant drugs themselves Phenobarbitone has been reported to have adverse effects on the developing brain including inhibition of brain growth20 neuronal toxicity21 and adverse behavioural and cognitive effects into adult life when administered to young animals22 Phenytoin shows unpredictable plasma levels and potential cardiotoxicity
Recent studies have shown an effect of AED exposure on the developing brain by causing neurodegeneration23 Phenytoin administration to immature rat pups at doses which produce serum levels similar to those achieved in human neonates was associated with widespread neuronal death as a result of apop-tosis (programmed cell death) Phenobarbitone had a similar effect when a dosage regimen similar to 40 mgkg was used and
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
this effect was maximal in the more immature brain Diazepam and clonazepam also resulted in a similar effect Midazolam and lidocaine were not tested in this study The combination of phenobarbitone or phenytoin with diazepam had a particularly profound effect on neurodegeneration
In summary recent data suggest that the commonly used AEDs for neonatal convulsions may in themselves cause neuro-degeneration due to apoptosis with lasting effects on develop-ment Many babies with neonatal convulsions are treated with at least two AEDs and this may produce more severe adverse effects than the seizures themselves
Practical management of neonatal seizures
Assimilation of these data and formulation of a rational policy is difficult when faced with a fitting neonate on an intensive care unit and pressure on the medical staff to lsquodo somethingrsquo but it is important to accept that sometimes doing nothing is preferable to using potentially dangerous drugs in a situation which does not warrant such intervention Many babies who have normal interseizure neurological clinical findings and whose seizures are relatively brief and infrequent probably do not need anticon-vulsant medication A normal or near-normal background EEG trace should reassure the clinician that anticonvulsants can be withheld
Some causes of neonatal convulsions are treatable such as meningitis hypoglycaemia hypocalcaemia and inborn errors of metabolism and each baby should be rapidly and carefully investigated for cause of the convulsions
In some babies clinical assessment of seizures is difficult ie when the baby is very sick small or paralyzed Sometimes it may be difficult to assess the significance of certain movement pat-terns Under these circumstances an EEG may prove to be very helpful In many units EEG is not available out of hours and a simple aEEG or CFM is strongly advised Modern instruments are very simple to apply and prolonged or frequent seizures should be identified with only moderate training The printout can be faxed to a more senior doctor if there is doubt as to what is shown on the trace
The balance of knowledge now is that frequent seizures cause additional damage to the developing brain and that treatment to abolish the seizures is warranted Unfortunately there is little evidence that the majority of seizures can be effectively termi-nated by current standard therapy Furthermore it appears that the more abnormal the background EEG the more difficult it is to control the seizures Nevertheless a written protocol for the management of neonatal convulsions is required on each unit Phenobarbitone and phenytoin remain the mainstay of treat-ment although their effectiveness is disappointing There is little to suggest that midazolam is more effective than lidocaine as third-line therapy but lidocaine is precluded if phenytoin has been previously used
In view of the anxiety as to the neurodegenerative effects on the immature brain of most anticonvulsants used in the neonatal period (particularly when multiple drugs are used) it is prefer-able to use only one drug to maximum dosage before introduc-ing a second In addition the duration of anticonvulsants should be minimized and the drugs stopped at the earliest opportu-nity It is my practice to stop anticonvulsants prior to discharge
paeDiatRiCS anD CHilD HealtH 184 18
from hospital if the baby is neurologically normal on clinical examination
REFEREnCES
1 Ronen gm penney S andrews W the epidemiology of clinical
neonatal seizures in newfoundland a population-based study
J Pediatr 1999 134 71ndash75
2 lanska mJ lanska DJ Baumann RJ et al a population-based study
of neonatal seizures in Fayette County Kentucky Neurology 1995
45 724ndash732
3 Rennie Jm Chorley g Boylan gB et al non-expert use of the
cerebral function monitor for neonatal seizure detection Arch Dis
Child Fetal Neonatal Ed 2004 89 F37ndashF40
4 tekgul H gauvreau K Soul J et al the current etoliologic profile
and neurodevelopmental outcome of seizures in term newborn
infants Pediatrics 2006 117 1270ndash1280
5 Surtees R Wolf n treatable neonatal epilepsy Arch Dis Child 2007
92 659ndash661
6 Ben-ari y Holmes gl effects of seizures on developmental
processes in the immature brain Lancet Neurol 2006 5 1055ndash
1063
7 Holmes gl gairsa Jl Chevassus-au-louis n et al Consequences of
neonatal seizures in the rat morphological and behavioral effects
Ann Neurol 1998 44 845ndash857
8 Stafstrom Ce Chronopoulos a thurber S et al age-dependent
cognitive and behavioural deficits following kainic-acid inducing
seizures Epilepsia 1993 34 420ndash432
9 Schmid R tandon p Stafstrom Ce et al effects of neonatal seizures
on subsequent seizure-induced brain injury Neurology 1999 53
1754ndash1761
10 Hoffmann aF Zhao Q Holmes gl Cognitive impairment following
status epilepticus and recurrent seizures during early development
support for the ldquotwo-hit hypothesisrdquo Epilepsy Behav 2004 5
873ndash877
11 Wirrell eC armstrong ea osman lD et al prolonged seizures
exacerbate perinatal hypoxic-ischemic brain damage Pediatr Res
2001 50 445ndash454
12 Carmo KB Barr p Drug treatment of neonatal seizures by
neonatologists and paediatric neurologists J Paediatr Child Health
2005 41 313ndash316
13 Hall Rt Hall FK Daily DK High-dose phenobarbital therapy in term
newborn infants with severe perinatal asphyxia a randomized
prospective study with three-year follow-up J Pediatr 1998 132
345ndash348
14 Boylan gB Rennie Jm pressler Rm et al phenobarbitone neonatal
seizures and video-eeg Arch Dis Child Fetal Neonatal Ed 2002 86
F165ndash170
15 painter mJ Scher mS Stein aD et al phenobarbital compared with
phenytoin for the treatment of neonatal seizures N Engl J Med
1999 341 485ndash489
16 Singh D Kumar p narang a a randomized controlled trial of
phenobarbital in neonates with hypoxic ischemic encephalopathy
J Matern Fetal Neonatal Med 2005 18 391ndash395
17 Castro Conde JR Borges H Domenech martinez e et al midazolam
in neonatal seizures with no response to phenobarbital Neurology
2005 64 876ndash879
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
18 malingre mm Van Rooij lgm Rademaker Cma et al Development
of an optimal lidocaine infusion strategy for neonatal seizures Eur
J Pediatr 2006 165 598ndash604
19 Sankar R painter mJ neonatal seizures after all these years we still
love what doesnrsquot work Neurology 2005 64 776ndash777
20 Diaz J Schain J Bailey Bg phenobarbital-induced brain growth
retardation in artificially reared rat pups Biol Neonate 1977 32 77ndash82
21 mattson RH phenobarbital toxicity in levy RH Dreifuss Fe
mattson RH et al eds antiepipeptic Drugs 3rd edn new york
Raven 1985 p 341ndash355
22 mikati ma Holmes gl Chronopoulos a et al phenobarbital
modifies seizure-related brain injury in the developing brain Ann
Neurol 1994 36 425ndash453
23 Bittigau p Sifringer m genz K et al antiepileptic drugs and
apoptotic neurodegeneration in the developing brain Proc Natl
Acad Sci U S A 2002 99 15089ndash15094
paeDiatRiCS anD CHilD HealtH 184 182
Practice points
bull the clinician needs to be aware that almost any repetitive
stereotype movement pattern can be a manifestation of
neonatal seizures
bull eeg is important in defining neonatal seizures
bull Frequent short-lived seizures have been shown to cause long-
term neurodevelopmental problems
bull Conventional anticonvulsant medication is ineffective in
abolishing neonatal seizures in greater than 50 of cases
bull there is evidence that exposure of the neonatal brain to
multiple anticonvulsants causes neuronal death
bull Future research is needed to evaluate more effective
anticonvulsants for treating this condition
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
Emotional support for families of sick neonatesMarina nicolaou
cristine Glazebrook
AbstractParents of sick neonates experience high levels of stress anxiety and
depression Most interventions with families of sick infants have focused
on fostering the motherndashinfant relationship through the provision of
information about infant developmental needs or through increased
motherndashinfant contact Many of these studies have reported improved
maternal well-being though there are some concerns about the scope
and practicality of large-scale interventions The few studies to have
prioritized emotional support for parents of sick neonates have pro-
duced encouraging results even interventions requiring relatively few re-
sources such as telephone support parent-to-parent support and group
support have been associated with reduced psychological morbidity for
parents The needs of parents can change throughout their infantrsquos hos-
pitalization and not all want or benefit from the provision of additional
support Thus neonatal intensive care units should aim to provide a
varied flexible and sustainable programme of support options Further
research should focus on the needs of fathers
Keywords mental health neonatal intensive care parents
The admission of an infant to neonatal care is acknowledged to be a source of considerable distress for families This review aims to explore evidence for the psychological impact on families of having an infant in neonatal intensive care and to identify evi-dence for the effectiveness of interventions to promote parental well-being It will conclude with recommendations for strategies to support parents of vulnerable infants and suggestions for fur-ther research
Psychological impact of neonatal care for parents
The majority of research examining the effect on parents of having a sick neonate has focused on families of premature or low birthweight infants Such research has found that parents with a sick neonate exhibit high levels of stress compared to normative samples and to parents of healthy full-term infants1 Singer et al2 examined the stress experienced by mothers of high-risk very low birthweight (VLBW) low-risk VLBW and term
Marina Nicolaou MPhil is a Teaching Assistant at the School of
Community Health Sciences University of Nottingham Nottingham UK
Cristine Glazebrook PhD is a Professor of Health Psychology at the School
of Community Health Sciences University of Nottingham Nottingham UK
PaeDiaTrics anD cHilD HealTH 184 196
infants Several self-report measures were used including the Brief Symptom Inventory the Parenting Stress Index (PSI) the Impact on Family Scale and the Family Inventory of Life Events and Changes (FILE) Mothers of VLBW infants had more psycho-logical distress at 1 month compared to mothers of term infants Mothers of high-risk VLBW infants also reported high psycho-logical distress at 2 years and high levels of parenting stress at 3 years Mothers have also been found to have higher stress levels compared to fathers Shaw et al3 examined the prevalence of acute stress disorder (ASD) in 40 parents whose infants were in the neonatal intensive care unit (NICU) Nearly half of the moth-ers (44) met the criteria for ASD although none of the fathers did Furthermore the severity of the symptoms (measured by the number of concurrent symptoms) was greater for the moth-ers than for the fathers3 The reasons behind this difference have been widely speculated with some believing that it is due to the mothersrsquo greater psychological involvement with the infant as evidenced by their general greater vulnerability to postpartum psychological disorder It could also reflect gender differences in coping style
Having an infant who requires intensive medical care repre-sents a significant emotional burden for families Not only is there extreme anxiety surrounding the infantrsquos health and distress for the childrsquos suffering there is also the unfamiliar and intimidating environment of the NICU to adjust to Hopper in her review of the literature identified sources of stress for parents of sick neo-nates as falling into three areas4 Situational factors included the severity of the infantrsquos illness and how parents adapted to the life crisis of having a sick infant Personal factors involved parental emotions about their roles and the instrumental and informa-tional support which were available to them The third area was classified as environmental sources of stress and included the environment of the NICU and the relationship between parents and members of staff This relationship has been examined by several studies in the nursing literature nurses are seen as ide-ally placed to provide the necessary support and information to parents with sick neonates However whilst some studies have shown that supportive and helpful hospital staff can have a posi-tive effect on parents other studies have highlighted the prob-lems and difficulties which can manifest It has been shown that parents and nurses often have very different ideas about issues eg the necessary skills and competencies needed in an NICU or the characteristics that make a lsquogood motherrsquo
Research has shown that there may be a relationship between high levels of parental stress and an increased likelihood of depression5 Postpartum depression is a psychiatric illness which appears in 10ndash15 of postpartum women Its reported preva-lence rates however have ranged from less than 10 up to 306 depending on the instruments used the population exam-ined and the timing of the research Several factors have been found to be associated with postpartum depression including poor social support and infant-related stressors6 Evidence indi-cates that postnatal depression may be underreported and this is of concern since the mental and psychological health of the mother can affect her relationship with her infant and thus the infantrsquos cognitive and emotional development5 Depressed moth-ers appear to look touch and talk to their infants less frequently and also appear to show fewer positive and more negative faces7 The vocalizations of mothers suffering with depression have also
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
been found to be less effective at promoting cognitive growth and learning in infants8
If researchers are interested in finding ways of providing sup-port for families of sick neonates then they must listen to what such families perceive their needs to be in order to avoid increas-ing anxiety and distress Furthermore the provision of appropri-ate support be it emotional informational or social will enhance parental coping abilities increase self-esteem and reduce anxiety It should be noted though that the research conducted around these issues has often taken lsquosupport needsrsquo as being synony-mous with lsquoinformation needsrsquo Such studies have examined the type the amount and quality of information that parents receive and perceive themselves as needing but have not explored in equal depth the perceived emotional support needs of families who have a sick infant In addition the needs of parents may change throughout their infantrsquos illness Ward examined the per-ceived needs of 52 parents of infants in an NICU9 Parents rated the needs of their hospitalized infant as most important along with the need to be reassured Interestingly they ranked their support needs as least important This research was conducted during the first week of the infantsrsquo hospitalization however which would explain the preoccupation of the parents with the infantrsquos health These results demonstrate that if researchers want to find ways of providing emotional support to parents of sick neonates they must be prepared not only to listen to parents but also to be flexible enough to satisfy the parentsrsquo changing needs and expectations
Interventions aimed at supporting parents
Most interventions that been evaluated in controlled studies have focused on supporting the motherndashinfant relationship and provid-ing information on infant development Many of these interven-tions have included the aim of improving the parental emotional state and thus psychological outcomes such as stress or anxi-ety have been assessed However few studies appear to include fathers This means that strategies implemented to provide emo-tional support to families of sick neonates are often derived from interventions tailored for mothers even though fathers may have different emotional needs
A wide range of interventions with mothers and infants has been evaluated in the NICU Increasing motherndashinfant contact through kangaroo care has been found to reduce maternal anxiety1011 and educational programmes delivered to fami-lies in the NICU have also been associated with reduced emo-tional difficulties in parents12ndash14 Kaaresen and colleagues implemented an intervention which consisted of eight sessions before discharge and four home visits all by trained nurses The sample included 71 premature infants in the intervention group 69 premature infants in the control group and 74 infants in the full-term control group The randomized controlled trial found that the intervention reduced parenting stress in both mothers and fathers of premature infants compared to controls to a level equivalent to parents in the term control group13 At 6 months corrected age mothers of preterm infants who had not received the intervention had total PSI scores which were 17 points higher than the mothers of infants born at term (an effect size of 057) A similar study evaluated the efficacy of an educationalndashbehavioural programmendashCreating Opportunities for
PaeDiaTrics anD cHilD HealTH 184 19
Parent Empowerment (COPE) ndash through a randomized controlled trial with 260 families of premature infants14 COPE was a four-phase educationalndashbehavioural programme which began as early as 2ndash4 d after mothers had given birth and continued until 1 week after discharge from the NICU The programme consisted of audiotaped and written infant behaviour information along with photographs which focused on common behaviours and characteristics of premature infants It also included various par-ent activities in the form of a four-phase workbook which aimed to assist mothers in the implementation of the experimental infor-mation COPE was found significantly to reduce maternal stress in the NICU as well as maternal anxiety and depressive symptoms after hospitalization In contrast a cluster randomized trial of a parenting intervention delivered to mothers of very premature infants from soon after birth showed no benefits for parenting stress1 The authors hypothesized that the intervention had not been of sufficient intensity particularly in the weeks surrounding discharge Neonatal care presents a significant barrier to parent-ing in the early weeks following a very preterm birth and so inter-ventions which focus on the developmental needs of infants and the parentndashchild relationship should particularly aim to support parents as they take on the parenting role There was also concern that the intervention had failed to reach those most at risk
Since large-scale projects can be costly to implement and may often fail to reach the families in most need it may be wiser to focus on intervention programmes which are more practical and easier to implement within a neonatal care setting Research has shown that even interventions which are based on one-off meet-ings with parents of sick neonates can be effective Jotzo and Poets examined the effect of an intervention programme aimed at reducing the severity of traumatic responses as a result of giv-ing birth prematurely15 Their programme consisted of a one-off intervention meeting along with additional psychological help throughout the hospitalization of the infant The meeting cov-ered a variety of issues including a reconstruction of the events shortly before and after the infantrsquos birth relaxation techniques discussion of coping strategies available resources and social support and support during emotional outbursts The measures used included the Impact of Event Scale (IES) and the Peritrau-matic Dissociative Experience Questionnaire At discharge the mothers who received the intervention were found to have a significantly lower traumatic impact as a result of premature birth Furthermore fewer mothers in the intervention group showed symptoms of clinically significant psychological trauma at discharge compared to mothers in the control group (36 vs 76)15 The lsquoParents Circle Programrsquo is another intervention with a similar structure16 This consisted of a 90 min session for parents with the aim of enhancing the developing relationship between parents and infants and to offer parents support A total of 104 parents (59 mothers and 45 fathers) and 44 members of hospital staff were asked to evaluate the programme and their results were analysed using content analysis Families reported gaining perspective on their situation feeling supported becom-ing aware of cues and optimizing interactions and becoming aware of available resources Parents and staff alike felt that participating in the intervention helped parents overcome the difficulties associated with the early time of their infantrsquos hos-pitalization Additional studies have also found positive results with fairly minimal interventions including discussion groups
7 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
in the NICU music during kangaroo care and pairing mothers of sick neonates with trained mothers who had been through similar experiences
Parent support programmes
Parent support programmes (PSPs) which are based in NICUs can provide parents with the opportunity to talk to parents who have been in similar situations and also to discuss their emo-tions with professionals who can help them cope with their situa-tion111718 The parent-to-parent support programme for mothers of preterm infants evaluated by Preyde and Ardal included edu-cational parental support group meetings and individual par-ent-to-parent support (primarily telephone support)19 Measures used included the Parental Stressor Scale NICU the State and the Trait Anxiety Inventories and the Beck Depression Inven-tory After 4 months of participation mothers in the intervention group reported lower levels of stress state anxiety and depres-sion compared to control group mothers The authors speculated however that the participants who were able to meet face to face with other parents were those who benefited the most Hurst conducted a comprehensive survey of an NICU-based PSP This PSP was provided in a variety of formats including a weekly parent support group hospital visitation and 24-h telephone sup-port20 Of the 477 participants 303 families used the PSP dur-ing a 2-year evaluation period with 78 using only one form of support and 18 using two forms Of a sub-sample of 48 parents asked to complete an evaluation of the PSP 92 stated that they would recommend such a programme to other parents Furthermore the majority of parents felt that it made them feel supported and helped them deal with their emotions20 This is an indication that such programmes can be very successful in sup-porting parents throughout their infantrsquos hospitalization It also shows that it can be beneficial to give parents several options and formats when it comes to such support services It is impor-tant to consider though that both the Hurst and the Preyde and Ardal studies found that some participants did not find the sup-port programmes helpful even reporting that they had caused them increased stress and anxiety Therefore it should not be assumed that support programmes will suit every individual and will provide the required support for all parents1920 NICUs need to be flexible enough to provide parents with a range of forms of support to choose from
The increased understanding of the strains that parents of sick neonates have to deal with has also led to efforts to improve customary practices in NICUs Family-centred care focuses on infants and their needs and attempts to redefine the relationship between parents and caregivers These practices strive to provide parents with support during their infantrsquos illness by focusing on freely sharing information and on the collaboration between parents and hospital staff Family-centred care has been found to be associated with several beneficial outcomes including improved parental satisfaction increased parental comfort staff satisfaction and decreased parental stress18 Research is already examining these practices and questioning how these can be improved further Such research reflects the increasing effort focused on lsquohumanizingrsquo the environment in NICUs in order to make parents feel more comfortable about spending time with their infants
PaeDiaTrics anD cHilD HealTH 184 19
Conclusion
Surprisingly few interventions have prioritized the provision of emotional support for parents of sick neonates or accounted for the changing needs and wishes of parents over the course of their infantrsquos care Large-scale supportive education-based inter-ventions have been shown to be effective in reducing parental distress However the feasibility and sustainability of such pro-grammes should also be considered Programmes which require significant additional resources can be expensive and there are also issues of training and quality control Interventions which require significant input from parents may also place additional burdens on families making them potentially less accessible to those most at risk Arguably the aim should be to explore ways of providing acceptable and effective informational support which could be complemented by emotional support from health professionals and from other parents in the unit Increasingly studies are exploring the use of computers and multimedia as an engaging flexible and cost-effective method of targeting indi-vidual needs and providing support and information Such com-puter-based and interactive multimedia interventions have been found to be successful with a range of patient groups and could therefore be examined as a complementary method of providing informational support to families with sick neonates
REfEREnCEs
1 Glazebrook c Marlow n israel c et al randomised trial of a
parenting intervention during neonatal intensive care Arch Dis Child
Fetal Neonatal Ed 2007 92 F438ndash443
2 singer lT salvator a Guo s collin M lilien l Baley J Maternal
psychological distress and parenting stress after the birth of a very
low-birth-weight infant JAMA 1999 281 799ndash805
3 shaw rJ Deblois T ikuta l Ginzburg K Fleisher B Koopman c
acute stress disorder among parents of infants in the neonatal
intensive care nursery Psychosomatics 2006 47 206ndash212
4 Hopper a sources of stress for parents of a sick neonate a
literature review Pediatr Nurs 2000 30 29ndash32
5 Davis l edwards H Mohay H wollin J The impact of very
premature birth on the psychological health of mothers Early Hum
Dev 2003 73 61ndash70
6 Bernazzani O saucier J-F David H Borgeat F Psychosocial
predictors of depressive symptomatology level in postpartum
women J Affect Disord 1997 46 39ndash49
7 Field T infants of depressed mothers Infant Behav Dev 1995 18
1ndash13
8 Kaplan Ps Bachorowski J-a Zarlengo-strouse P child-directed
speech produced by mothers with symptoms of depression fails
to promote associative learning in 4-month-old infants Child Dev
1999 70 560ndash570
9 ward K Perceived needs of parents of critically ill infants in
a neonatal intensive care unit (nicU) Pediatr Nurs 2001 27
281ndash286
10 lai Hl chen cJ Peng Tc et al randomized controlled trial of music
during kangaroo care on maternal state anxiety and preterm infantsrsquo
responses Int J Nurs Stud 2006 43 139ndash146
8 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
11 Tallandini Ma scalembra c Kangaroo mother care and mother-
premature infant dyadic interaction Infant Ment Health J 2006 27
251ndash275
12 Ohgi s Fukuda M akiyama T Gima H effect of an early intervention
programme on low birthweight infants with cerebral injuries
J Paediatr Child Health 2004 40 689ndash695
13 Kaaresen Pi ronning Ja Ulvund se Dahl lB a randomized
controlled trial of the effectiveness of an early-intervention program
in reducing parenting stress after preterm birth Pediatrics 2006
118 e9ndash19
14 Melnyk BM Feinstein nF alpert-Gillis l et al reducing premature
infantsrsquo length of stay and improving parentsrsquo mental health
outcomes with the creating opportunities for parent empowerment
(cOPe) neonatal intensive care unit program a randomized
controlled trial Pediatrics 2006 118 e1414ndash1427
15 Jotzo M Poets cF Helping parents cope with the trauma of
premature birth an evaluation of a trauma-preventive psychological
intervention Pediatrics 2005 115 915ndash919
16 Pearson J andersen K evaluation of a program to promote positive
parenting in the neonatal intensive care unit Neonatal Netw 2001
20 43ndash48
17 roman l lindsay J Boger r et al Parent-to-parent support
initiated in the neonatal intensive care unit Res Nurs Health 1995
18 385ndash394
18 Meyer ec coll cTG lester BM Boukydis cFZ McDonough sM Oh w
Family-based intervention improves maternal psychological well-
being and feeding interaction of preterm infants Pediatrics 1994
93 241ndash246
PaeDiaTrics anD cHilD HealTH 184 19
19 Preyde M ardal F effectiveness of a parent ldquobuddyrdquo program for
mothers of very preterm infants in a neonatal intensive care unit
CMAJ 2003 168 969ndash973
20 Hurst i One size does not fit all Parentsrsquo evaluations of a support
program in a newborn intensive care nursery J Perinat Neonatal
Nurs 2006 20 252ndash261
Practice points
bull Parents of sick neonates experience significant distress and
exhibit higher levels of stress anxiety and depression than
parents of healthy infants
bull educational support emotional support and increased
motherndashinfant contact have been shown to promote maternal
well-being
bull emotional support for fathers has been largely neglected in
the research literature
bull Parents benefit from a choice of supportive facilities which
could include face-to-face sessions with health professionals
telephone support hospital visitation parent-to-parent
support and unit-based group support meetings
bull Parentsrsquo support needs can change during their infantrsquos
hospitalization and not all parents want or benefit from the
provision of additional information and emotional support in
the neonatal unit
9 copy 2008 elsevier ltd all rights reserved
Personal Practice
When should enteral feeds be started in preterm infantsnicholas D embleton
AbstractPaediatricians are regularly faced with the question of when best to start
enteral feeds in preterm infants this is important as longer term out-
come may be compromised by sub-optimal nutrition in early life clinical
factors that may affect the decision to start and the risk and benefits
are discussed
Keywords breast milk feeding nutrition parenteral nutrition
Key points in the history
Alice is lsquonutritionally vulnerablersquo and whilst this may not be immediately apparent it will affect her long term outcome Her energy stores are extremely limited and consist primarily of pro-tein She has less than 5 fat and little energy associated with stored glycogen She is losing about 1 gkgd protein equivalent so she needs at least that and a minimum of 50ndash60 kcalkg of energy just to maintain the status quo let alone grow
Her weight is on the 25th centile Review of any antenatal his-tory may reveal whether fetal growth was normal Fetal growth retardation can occur with a weight greater than 10th centile The presence of antenatal absent or reversed end diastolic flow in the umbilical artery indicates poor gut blood flow This increases the risk of necrotizing enterocolitis (NEC) and might suggest a more cautious approach to starting feeds1
She has no important cardiovascular problems but if she were hypotensive gut blood flow may be low There is no umbilical
Nicholas D Embleton BSC (Hons) MBBS (Hons) MD FRCPCH is Consultant in
Neonatal Medicine at Newcastle Neonatal Service Royal Victoria
Infirmary Newcastle upon Tyne NE1 4LP UK
Should you start feeds at a day of age
alice was born following spontaneous labour at 30 weeksrsquo
gestation she weighed 1300 g and is now 18 h old she was
briefly ventilated and then extubated to continuous positive
airway pressure 12 h ago in 35 oxygen she has had caffeine
citrate but still has intermittent episodes of self-correcting
apnoea she was commenced on iv 10 dextrose but this was
replaced by a parenteral amino acid solution (referred to as
lsquotPnrsquo) along with intralipid at 0900 this morning serum glucose
is 11 mmoll and blood pressure is 42 systolic
PaeDiatrics anD cHilD HealtH 184 20
arterial catheter in situ but there is no good evidence that this should delay the decision to start feeds Her glucose is high but this is quite common in a baby like this Could this be a sign of sepsis Caffeine does not affect the incidence of NEC2 The great-est risk factor for NEC in this case is prematurity
What else might be found on examination
Up until 24 h ago she was swallowing large amounts of amniotic fluid What will have changed since then
General examination should confirm peripheral perfusion lsquogestaltrsquo view (does she look lsquowellrsquo) and cardiovascular status lsquoBowel soundsrsquo are not usually helpful
The most important variable likely to affect gut perfusion is the arterial duct Precordial lsquoheaversquo and a loud murmur are sug-gestive but it is possible to have a significant ductal shunt in a baby with a normal examination Cardiac ultrasound will con-firm this diagnosis It might be better to treat a large shunt first with indometacin and to delay starting feeds for a further 24 h
It is not possible to assess gut perfusion clinically but normal perfusion elsewhere (adequate urine output usually indicates adequate renal perfusion) would be reassuring Most preterm babies have a few abdominal lsquoloopsrsquo visible but a distended abdomen with many palpable loops suggests ileus This might be secondary to sepsis or poor gut blood flow Preterm babies do not pass much meconium in the first 24ndash48 h
Balance of risks between starting and withholding feeds
Alice requires 35ndash4 gkgd of protein and 120 kcalkgd to grow3 This will initially be provided parenterally Delaying feeds increases the risk of gut villous atrophy and prolongs the need for lsquototal parenteral nutrition (TPN)rsquo TPN requires intravenous access and so increases the risk of sepsis and when prolonged use is required combined with the lack of enteral feeding may result in hepatic impairment
Delaying feeds may allow a gut that has been chronically under-perfused to re-establish more normal perfusion although normal gut endocrine function digestive enzyme upregulation and motility require a source of intraluminal nutrients1 A recent study suggested benefit from delaying the introduction of feeds4 but methodologi-cal problems exist5 Although a Cochrane meta-analysis suggested no benefit only two studies were included6 A large UK-based trial is examining the effect of early or late feeding in preterm infants who were born growth retarded following identification of antena-tal absent or reversed end diastolic flow in the umbilical artery7
When starting feeds what volume should be used
There are no good data to guide this decision We start with 24 mlkg (1 mlkgh) and then increase by this amount each day Most babies achieve full enteral feeds (ge150 mlkgd) by a week of age Feeding guidelines improve the outcome8 Measure-ment or assessment of gastric aspirates is not consistently useful in predicting subsequent feeding intolerance or development of NEC Aspirate volumes equivalent to or sometimes greater than the amount given in the preceding 1ndash2 h are usually normal Most aspirates have a greenish colour Thick bloody or intensely bile-stained aspirates require detailed assessment
0 copy 2008 elsevier ltd all rights reserved
Personal Practice
What else affects decisions and outcome
Feeding success is affected by sepsis and NEC Scrupulous atten-tion should be paid to hand washing and intravenous access and blood sampling should be minimized There is no good evidence to support the routine use of pro-kinetic agents or H2 blockers
The most important clinical intervention affecting the occur-rence of NEC is the use of breast milk9 All efforts should be directed at persuading parents of the benefits and supporting the process Some clinicians delay starting feeds for a further 24 h whilst expressed breast milk becomes available Donor breast milk might be equally efficacious10
RefeRenceS
1 Dorling J Kempley s leaf a Feeding growth restricted preterm
infants with abnormal antenatal Doppler results Arch Dis Child Fetal
Neonatal Ed 2005 90 F359ndash363
2 schmidt B roberts rs Davis P et al caffeine therapy for apnea of
prematurity N Engl J Med 2006 354 2112ndash2121
PaeDiatrics anD cHilD HealtH 184 20
3 embleton nD Pang n cooke rJ Postnatal malnutrition and growth
retardation an inevitable consequence of current recommendations
in preterm infants Pediatrics 2001 107 270ndash273
4 Berseth cl Bisquera Ja Paje VU Prolonging small feeding volumes
early in life decreases the incidence of necrotizing enterocolitis in
very low birth weight infants Pediatrics 2003 111 529ndash534
5 Menon G Boyle eM embleton nD et al introduction of enteral
feeds in preterm infants Pediatrics 2004 114 327ndash328
6 Kennedy Ka tyson Je chamnanvanikij s early versus delayed
initiation of progressive enteral feedings for parenterally fed low
birth weight or preterm infants Cochrane Database Syst Rev 2000
cD001970
7 wwwnpeuoxacukadept
8 Patole sK de Klerk n impact of standardised feeding regimens on
incidence of neonatal necrotising enterocolitis a systematic review
and meta-analysis of observational studies Arch Dis Child Fetal
Neonatal Ed 2005 90 F147ndash151
9 lucas a cole tJ Breast milk and neonatal necrotising enterocolitis
Lancet 1990 336 1519ndash1523
10 Boyd ca Quigley Ma Brocklehurst P Donor breast milk versus
infant formula for preterm infants systematic review and meta-
analysis Arch Dis Child Fetal Neonatal Ed 2007 92 F169ndash175
1 copy 2008 elsevier ltd all rights reserved
self-assessment
Case 1A term male infant born to consanguineous parents is assessed at 24 h of age due to poor feeding profuse yellow watery diar-rhoea and irritability He weighed 32 kg at birth and delivery was uneventful There was no polyhydramnios He has been breastfed since birth On examination he is pale with a non-tender but distended abdomen and reduced bowel sounds His weight is 275 kg and he looks dehydrated Examination is otherwise normal
Initial investigations (normal values in parentheses) showed
sodium 149 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 65 mmollitre (25ndash75)
creatinine 147 μmollitre (40ndash110)
chloride 119 mmollitre (95ndash105)
haemoglobin 172 gdl (140ndash200)
White blood cell count 80 times 109litre (100ndash260)
Platelet count 302 times 109litre (150ndash400)
arterial blood gas
ph 720 (730ndash745)
PcO2 23 kPa (46ndash60)
Bicarbonate 68 mmollitre (220ndash260)
Base excess minus186 mmollitre (minus20 to +20)
lactate 59 mmollitre (06ndash24)
An abdominal X-ray shows distended bowel loops with no intramural thickening or pneumoperitoneum (Figure 1)
He was given nil by mouth and received intravenous fluids and antibiotics His dehydration improved but the metabolic acidosis and diarrhoea persisted despite receiving no enteral feeds and the commencement of total parenteral nutrition Blood and stool cultures were negative
1 Which of the following best describes these results Choose ONE answer ONLY from the followingA Hypernatraemia hyperchloraemic metabolic acidosis
with increased anion gapB Hypernatraemia hyperchloraemic metabolic acidosis
with normal anion gap
Manish Sadarangani BM BCh MA MRCPCH is Clinical Research Fellow
at the Department of Paediatrics University of Oxford Centre for
Clinical Vaccinology and Tropical Medicine Churchill Hospital
Oxford OX3 7LJ UK
Shabna Rajapaksa MB BChir MA MRCPCH is Specialist Registrar in
Paediatrics at the Paediatric Intensive Care Unit John Radcliffe
Hospital Oxford OX3 9DU UK
Nicholas Mann MD FRCP FRCPCH DCH is Consultant Paediatrician at the
Department of Paediatrics Royal Berkshire Hospital Reading RG1
5AN UK
self-assessment
C Hypernatraemic dehydration and compensated metabolic acidosis
D Acute renal failureE Renal tubular acidosis
2 What is the likely diagnosis Choose ONE answer ONLY from the followingA Hirschsprung disease ndash long segmentB Cystic fibrosis with meconium ileusC Microvillus inclusion diseaseD Cowrsquos milk protein intoleranceE Lactose intolerance
3 What is the investigation of choice Choose ONE answer ONLY from the followingA Rectal biopsy with staining for acetylcholine receptorsB Immunoreactive trypsinC Gastrointestinal endoscopy and biopsyD Stool microscopy and cultureE Stool reducing substances
Case 2A 4-year-old boy presents with a 3 d history of jaundice and a florid rash He has had orange urine and there is no change in his stool colour His family originate from Kosovo and have lived in the UK for the last 8 years He has never left the UK There is no history of blood transfusion or sex-ual abuse The grandmother was recently diagnosed with hepatitis B
On examination he is well apyrexial and mildly jaundiced with cervical and axillary lymphadenopathy He has an exten-sive papular rash over the face extremities and trunk (Figure 2) There is 3 cm hepatomegaly with no splenomegaly or ascites Examination is otherwise normal
Figure 1 abdominal X-ray of baby
Paediatrics and child health 184 202 copy 2008 elsevier ltd all rights reserved
self-assessment
Initial investigations are as follows
haemoglobin 110 gdl (113ndash135)
White blood cell count 108 times 109litre (50ndash150)
Platelet count 278 times 109litre (150ndash400)
inr 10 (08ndash12)
aPt ratio 10 (08ndash13)
sodium 140 mmollitre (135ndash145)
Potassium 42 mmollitre (35ndash50)
Urea 56 mmollitre (25ndash75)
creatinine 65 μmollitre (45ndash120)
total bilirubin 66 μmollitre (0ndash15)
conjugated bilirubin 23 μmollitre (0ndash10)
alanine aminotransferase (alt) 2033 iUlitre (0ndash35)
alkaline phosphatase 987 iUlitre (71ndash234)
Gamma-glutamyl transferase (GGt) 870 iUlitre (0ndash51)
1 What is the name of this rash Choose ONE answer ONLY from the followingA Erythema multiformeB Erythema migransC GianottiminusCrosti syndromeD EczemaE Dermatitis herpetiformis
2 What is the most likely diagnosis Choose ONE Answer ONLY from the followingA Autoimmune hepatitisB Hepatitis BC Hepatitis DD Wilson diseaseE Alpha-1 antitrypsin deficiency
3 What is the best means of management Choose ONE answer ONLY from the followingA Isolation until the jaundice disappearsB ImmunosuppressionC Copper chelating agents and genetic counsellingD Patient and family education with consideration of
antiviral agentsE Liver transplantation
Case 3A 10-month-old boy presents with 3 weeks of vomiting and constipation ndash he is passing hard stools every 2ndash3 days He has fallen from the 9th to below the 04th centile in the last 6 weeks He passed meconium within the first 24 h of life On examina-tion he looks pale and there are some dysmorphic features ndash a short nose long philtrum and wide mouth He has normal heart sounds with a grade 3 ejection systolic murmur loudest at the upper right sternal edge Examination is otherwise normal
Initial investigations are as follows
haemoglobin 91 gdl (113ndash141)
total white blood cell count 124 times 109litre (60ndash170)
Platelet count 407 times 109litre (150ndash400)
sodium 144 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 78 mmollitre (25ndash75)
creatinine 78 μmollitre (45ndash120)
albumin 52 glitre (35ndash50)
corrected calcium 384 mmollitre (238ndash263)
Phosphate 167 mmollitre (099ndash157)
1 What is the most likely diagnosis Choose ONE answer ONLY from the followingA HyperparathyroidismB Acute leukaemiaC Williams syndromeD Hypervitaminosis DE Familial hypocalciuric hypercalcaemia
2 Which investigation would be most useful in establishing the diagnosis Choose ONE answer ONLY from the followingA Intact parathyroid hormone assayB Blood filmC Fluorescent in-situ hybridization for 7q1123 deletionD 25-hydroxyvitamin D assayE Urine calciumcreatinine ratio
3 Which of the following treatments would not be suitable for this patient Choose ONE answer ONLY from the followingA Low calcium dietB Normal saline infusionC FurosemideD CorticosteroidsE Bisphosphonates
Case 4A 10-week-old girl presents with a 2-day history of poor feed-ing Her mother has been concerned about weakness since birth She only has a flicker of movement in the arms none in the legs and has a weak cry She has been passing urine and opening her bowels normally She was born at full term by normal delivery and did not require any resuscitation at birth Normal fetal movements were felt antenatally and there was no polyhydramnios She is the first child of non- consanguineous parents and there is no significant family his-tory On examination she is alert and fixing and following appropriately She has a weak cry and a weak suck There is reduced central and peripheral tone with marked head lag
Figure 2 rash found on examination
Paediatrics and child health 184 203 copy 2008 elsevier ltd all rights reserved
self-assessment
Muscle power is grade 3 out of 5 in the arms and legs There is no muscle or tongue fasciculation and she has absent reflexes throughout The remainder of the examination is normal
Electromyogram shows irregular polyphasic motor unit potentials with marked instability consistent with a dener-vating and re-innervating process (Figure 3)
1 Which of the following additional investigations may be helpful Choose ONE answer ONLY from the followingA Nerve conduction studiesB Creatine kinase assayC Muscle biopsyD SMN1 gene analysisE All of the above
2 What is the most likely cause of this childrsquos symptoms Choose ONE answer ONLY from the followingA Congenital myotonic dystrophyB Duchenne muscular dystrophyC PraderminusWilli syndromeD Spinal muscular atrophyE Mitochondrial myopathy
3 What is the mode of inheritance of this disease Choose ONE answer ONLY from the followingA X-linked recessiveB Autosomal recessiveC Autosomal dominantD MitochondrialE Sporadic
Case 5A 13-year-old girl presents with a 3-week history of fever up to 40degC night sweats and headache She has a reduced appetite with some weight loss She has no other specific symptoms She was on holiday in China 7 months ago On examination she looks well and has a temperature of 387degC There is no lymphadenopathy and no rashes Examination is entirely normal
Results of investigations are as follows
haemoglobin 126 gdl (120ndash160)
total white blood cell count 132 times 109litre (43ndash108)
neutrophil count 115 times 109litre (25ndash75)
Platelet count 244 times 109litre (150ndash400)
Blood film neutrophilia with left shift
erythrocyte sedimentation rate 63 mmh (1ndash20)
c-reactive protein 219 mglitre (0ndash5)
Blood culture Streptococcus intermedius
from anaerobic bottle only
csf culture negative
Magnetic resonance imaging (MRI) of the brain shows acute frontal sinusitis with a large intracranial frontal extra-dural empyema (Figure 4)
1 Which of the following would be appropriate management Choose ONE answer ONLY from the followingA A 12-week course of intravenous antibioticsB Drainage of the frontal sinus followed by 2 weeks of
intravenous antibioticsC Drainage of the empyema followed by 2 weeks of
intravenous antibioticsD Drainage of the empyema and the frontal sinus
followed by 2 weeks of oral antibiotics
1151
1152
1153
1154
1155
1156
1157
1158
1159
1200
50ms 1mV
Figure 3 electromyogram recording from the patient Figure 4 Parasagittal section from mri scan of patient
Paediatrics and child health 184 204 copy 2008 elsevier ltd all rights reserved
self-assessment
E Drainage of the empyema and the frontal sinus followed by 8 weeks of intravenous antibiotics
2 Streptococcus intermedius is a potential pathogen in which of the following infections Choose ONE answer ONLY from the followingA Liver abscessB Urinary tract infectionC MeningitisD Thoracic empyemaE Pneumonia
3 Which of the following statements regarding lsquopyrexia of unknown originrsquo in children is false Choose ONE answer ONLY from the followingA Malignancy is the underlying pathology in 5ndash15 of
casesB An aetiology will be found in over 90 of casesC The most common cause is infectionD A rheumatological cause is found in 10ndash20 of casesE Familial Mediterranean fever can occur in children of
non-Mediterranean ethnicity
Answers
Case 11 AThe anion gap is a useful tool to differentiate the causes of a metabolic acidosis It is calculated by the equation
Anion gap = [Na K ] [Cl HCO ]3+ + minus minus+ minus +
It represents the effect of unmeasured anions on the plasma pH and is normally 10ndash18 mmollitre
2 CMicrovillus inclusion disease is a severe autosomal recessive enteropathy that is typically apparent within hours or days after birth It is the second most common cause of protracted diarrhoea in the newborn after infectious causes It is characterized by severe yellow watery diarrhoea and malabsorption due to hypoplasia andor atrophy of the villi of the small intestine secondary to an inherited defect in the brush border membrane This results in severe dehydration malnutrition and metabolic acidosis due to bicarbonate loss from the gut
3 CDiagnosis of microvillus inclusion disease is made on small bowel biopsy Electron microscopy findings are of intracellular brush border inclusions and densely packed apical cytoplasmic vesicular bodies indicating microvillous atrophy There is no cure Treatment is supportive with total parenteral nutrition and consideration of small bowel transplantation
Further reAding
Goulet O ruemmele f causes and management of intestinal failure
in children Gastroenterology 2006 130(suppl 1) s16ndash28
rhoads Jm Vogler rc lacey sr et al microvillus inclusion disease
In vitro jejunal electrolyte transport Gastroenterology 1991
100 811ndash817
Case 21 CGianottindashCrosti syndrome is a distinct self-limiting rash commonly associated with viral infections in children between 2 and 6 years of age It presents as multiple pink to redminusbrown papules or papulovesicles which may be pruritic and can become confluent Gianotti and Crosti initially described the exanthema as associated with hepatitis B virus and they termed it papular acrodermatitis of childhood It can occur in several viral diseases eg hepatitis A B and C coxsackie viruses and cytomegalovirus
2 BHepatitis is a syndrome characterized by inflammation or injury of liver cells which may develop into cell necrosis and subsequently fibrosis andor cirrhosis Biochemically there are raised liver enzymes The degree of transaminase elevation does not correlate with the severity of the disease process Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of viral hepatitis
3 DHepatitis B infection is transmitted via blood sexually or vertically Infection may be acute or chronic Diagnostic markers are the presence of surface antigen (HBsAg) and HBV DNA The presence of e antigen (HBeAg) indicates high infectivity Infected newborns have a 95 risk of becoming carriers this risk decreases with infection acquired later in childhood Approximately 15ndash25 of HBV carriers will die from cirrhosis or hepatocellular carcinoma Extrahepatic findings are more common in older children and include membranous glomerulonephritis and GianottiminusCrosti syndrome Fulminant hepatic failure occurs in severe cases resulting in persistent jaundice encephalopathy and coagulopathy Management includes counselling family members monitoring for ongoing liver disease and consideration of antiviral therapy
Further reAding
Brandt O abeck d Gianotti r Burgdorf W Gianotti crosti
syndrome J Am Acad Dermatol 2006 54 136ndash145
slowik mK Jhaveri r hepatitis B and c viruses in infants and
young children Semin Pediatr Infect Dis 2005 16 296ndash305
Case 31 CHypercalcaemia is uncommon in infancy The most common symptoms in this age group are irritability vomiting and constipation It may be a manifestation of Williams syndrome vitamin D or calcium excess as well as disorders associated with reduced bone formation such as hypophosphatasia or increased bone resorption such as malignancy Occasionally
Paediatrics and child health 184 205 copy 2008 elsevier ltd all rights reserved
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-
SympoSium neonatology
canopy This will reduce radiative heat losses and the incubator air temperature may have to be reduced to prevent a rise in the babyrsquos temperature
Transepidermal water loss and skin maturationTransepidermal movement of water is essential for the acceler-ated maturation of the skin of the immature baby40 It also helps in maintaining the epidermal barrier function41
Use of high ambient humidity in nursing preterm babies under 28 weeksrsquo gestation has been shown to reduce the rate of promo-tion of skin barrier development42
More work in the immature baby is needed to determine the optimum level and duration of environmental humidity as well as the associated benefits and risks of use and the effects of humidification on clinically important outcomes43
Temperature monitoring and its interpretation
The concept of the neutral thermal environment in which a baby uses a minimum of energy to maintain thermal stability has proven useful in determining the optimum environmental temperature for nursing the newborn baby4445 The published data are now old and do not include any allowance for added humidity This makes them less useful in the care of the very immature baby
The way a baby interacts with their environment is always changing and whatever settings are first used it is necessary to monitor continuously the thermal balance Continuous mea-surement of oxygen consumption to allow calculation of energy expenditure is not practical and in normal day-to-day care tem-perature monitoring is the only means of assessing the thermal stability of the baby
There is no single deep body temperature as this will vary depending on the metabolic rate of a particular tissue The brain has the highest temperature of any organ within the body It is however possible to find a central temperature that is representa-tive of deep body temperature Trends in this temperature reflect changes in the deep body temperatures of the body at least with sufficient accuracy for day-to-day clinical care
Traditionally rectal temperature has been used as the mea-sure of deep body temperature This is still used commonly in many countries but less so in UK There is a significant risk of damage to the mucosa of the rectum Also rectal temperature is unreliable being affected by the depth of insertion of the ther-mometer whether the baby has just passed a stool and by the temperature of the blood returning from the lower limbs It is difficult to retain the probes in the same position making this an unreliable site for continuous temperature monitoring
The temperature in the oesophagus at the level of the heart gives a measure of the temperature of the blood in the great veins returning from the body This is possibly the best overall representation of the lsquodeep body temperaturersquo Measurement of oesophageal temperature is however very invasive and not suit-able for clinical monitoring
The temperature of the skin over the liver or in the axilla reflects central temperature Actual values will be lower than the deep body temperatures but in the immature baby these sites can be used to show the trend in central temperature A more accurate measurement can be obtained by placing the
paeDiatRiCS anD CHilD HealtH 184 15
probe between the scapulae and a non-conducting mattress No tape is needed on the skin as the baby lies on the probe holding it in place If the probe is over an area of skin from which no heat can be lost by conduction convection radia-tion or evaporation then with heat flow from the centre of the body to the skin down a temperature gradient this area of skin will warm up to the same temperature as the bodyrsquos core This so-called zero heat flux temperature has been shown to be very close to the central temperature as measured by an oesophageal probe46
The measurement of a single temperature tells us how well the baby is maintaining that temperature but nothing about how much energy is being used to achieve thermal balance The continuous measurement and display of a central (abdominal axilla or zero heat flux) and a peripheral (sole of the foot) tem-perature detects cold stress with the peripheral temperature fall-ing before the central measurement changes
The preterm baby who appears to be comfortable in their environment will have a central temperature measured from a skin probe of 368ndash373 degC and a centralndashperipheral temperature difference of 05ndash1 degC An increasing centralndashperipheral tempera-ture difference particularly above 2 degC is usually due to cold stress and occurs before any fall in central temperature12
Hypovolaemic babies will vasoconstrict their peripheral circu-lation in an attempt to maintain blood pressure This results in an increase in the centralndashperipheral temperature difference but in such cases there are usually other signs of hypovolaemia such as rising heart rate and falling blood pressure12
A high central temperature particularly if unstable along with a wide centralndashperipheral gap is seen in septic babies47
Conclusion
Although we have known for a very long time the importance of maintaining the temperature of the newborn we are still faced with new challenges in the care of the sick immature baby Tem-perature control during their period of adaptation to extrauterine life is often poor and allowing these vulnerable babies to cool is associated with adverse outcome Simple measures can prevent hypothermia following delivery If cold at birth is associated with poor outcome there is no reason to believe that preventing ther-mal stress is any less important once the baby is in the neonatal unit It is important that the risks and benefits associated with various methods of controlling the infantrsquos temperature are fully understood
RefeRenCeS
1 Cone te perspectives in neonatology in Sith gF Vidyasagar D eds
Historical Review and Recent advances in neonatal and perinatal
medicine mead Johnson nutritional Division 1983 p 9ndash33
2 Silverman Wa Fertig JW Berger ap the influence of the thermal
environment upon survival of newly born preterm infants Pediatrics
1958 22 876ndash885
3 Silverman Wa agate FJ Fertig JW a sequential trial of the
nonthermal effect of atmospheric humidity on survival of human
infants of low birth weight Pediatrics 1963 31 710ndash724
8 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
4 Costeloe K Hennessy e gibson at marlow n Wilkinson aR for the
epiCure Study group the epiCure study outcomes to discharge
from hospital for infants born at the threshold of viability Pediatrics
2000 196 659ndash671
5 CeSDi project 2728 available from wwwcemachorguk
publicationsp2728mainreportpdf
6 parry g tucker J tarnow-mordi W for the uK neonatal Staffing
Study Collaborative group CRiB ii an update of the clinical risk
index for babies score Lancet 2003 361 1789ndash1791
7 Richardson DK Corcoran JD escobar gJ et al Snap-ii and Snappe-ii
simplified newborn illness severity and mortality risk scores
J Pediatr 2001 138 92ndash100
8 Wyatt JS gluckman pD liu py et al CoolCap Study group
Determinants of outcomes after head cooling for neonatal
encephalopathy Pediatrics 2007 119 912ndash921
9 yager Jy armstrong ea Jaharus C Saucier Dm Wirrell eC preventing
hyperthermia decreases brain damage following neonatal-ischemic
seizures Brain Res 2004 1011 48ndash57
10 Harned Jr HS Herrington Rt Ferreiro Ji the effects of immersion
and temperature on respiration in newborn lambs Pediatrics 1970
45 598ndash605
11 laptook aR Salhab W Bhaskar B neonatal Research network
admission temperature of low birth weight infants predictors and
associated morbidities Pediatrics 2007 119 e643ndash649
12 lyon aJ pikaar me Badger p mcintosh n temperature control in
infants less than 1000g birthweight in the first 5 days of life Arch
Dis Child 1997 76 F47ndash50
13 Vohra S Roberts RS Zhang B Janes m Schmidt B Heat loss
prevention (Help) in the delivery room a randomized controlled
trial of polyethylene occlusive skin wrapping in very preterm infants
J Pediatr 2004 145 750ndash753
14 lyon aJ Stenson B Cold comfort for babies Arch Dis Child Fetal
Neonatal Ed 2004 89 F93ndash94
15 Stothers JK Head insulation and heat loss in the newborn Arch Dis
Child 1981 56 530ndash534
16 newton t Watkinson m preventing hypothermia at birth in
preterm babies at a cost of overheating some Arch Dis Child Fetal
Neonatal Ed 2003 88 F256
17 Smith Cl Quine D mcCrosson F armstrong l lyon a Stenson B
Changes in body temperature after birth in preterm infants
stabilised in polythene bags Arch Dis Child Fetal Neonatal Ed 2005
90 F444
18 mcCall em alderdice Fa Halliday Hl Jenkins Jg Vohra S
interventions to prevent hypothermia at birth in preterm andor low
birthweight babies Cochrane Database of Systematic Reviews 2005
issue 1 art noCD004210 doi10100214651858CD004210pub2
19 meyer mp Bold gt admission temperatures following radiant
warmer or incubator transport for preterm infants lt 28 weeks
a randomised study Arch Dis Child Fetal Neonatal Ed 2007 92
F295ndash297
20 Carmichael a mcCullough S Kempley St Critical dependence of
acetate thermal mattress on gel activation temperature Arch Dis
Child Fetal Neonatal Ed 2007 92 F44ndash45
21 Hey en the care of babies in incubators in gairdner D Hull D
eds Recent advances in paediatrics 4th edn london J amp a
Churchill 1971 p 171ndash216
22 Whitelaw a Heisterkamp g Sleath K acolet D Richard m Skin-to-
skin contact for very low birthweight infants and their mothers Arch
Dis Child 1988 63 1377ndash1381
paeDiatRiCS anD CHilD HealtH 184 15
23 Bauer K pyper a Sperling p uhrig C Versmold H effects of
gestational and postnatal age on body temperature oxygen
consumption and activity during early skin-to-skin contact between
preterm infants of 25ndash30-week gestation and their mothers Pediatr
Res 1998 44 247ndash251
24 Hey en Katz g orsquoConnell B the total thermal insulation of the
newborn baby J Physiol 1970 207 683ndash689
25 Hey en temperature regulation in sick infants in tinker J Rapin m
eds Care of the Critically ill patient Berlin Springer 1983 p
1013ndash1029
26 leBlanc mH Relative efficacy of an incubator and an open warmer
in producing thermoneutrality for the small premature infant
Pediatrics 1982 69 439ndash445
27 meyer mp payton mJ Salmon a Hutchinson C deKlerk a
a clinical comparison of radiant warmer and incubator care for
preterm infants from birth to 1800grms Pediatrics 2001 108
395ndash401
28 Silverman Wa Blanc Wa effect of humidity on survival of newly
born premature infants Pediatrics 1957 20 477ndash487
29 Hammarlund K Sedin g transepidermal water loss in newborn
infants iii relation to gestational age Acta Paediatr Scand 1979
68 795ndash801
30 Hammerlund K Stroumlmberg B Sedin g Heat loss from the skin of
preterm and fullterm newborn infants during the first weeks after
birth Biol Neonate 1986 50 1ndash10
31 Kalia yn nonata lB lund CH guy RH Development of skin
barrier function in premature infants J Invest Dermatol 1998 111
320ndash326
32 Kjartansson S arsan S Hammarlund K Sjoumlrs g Sedin g Water loss
from the skin of term and preterm infants nursed under a radiant
heater Pediatr Res 1995 37 233ndash238
33 mok Q Bass Ca Ducker Da mcintosh n temperature instability
during nursing procedures in preterm neonates Arch Dis Child
1991 66 783ndash786
34 mancini aJ Sookdeo-Drost S madison KC Smoller BR lane at
Semipermeable dressings improve epidermal barrier function in
premature infants Pediatr Res 1994 36 306ndash314
35 Donahue ml phelps Dl Richter Se Davis Jm a semipermeable skin
dressing for extremely low birth weight infants J Perinatol 1996 16
20ndash26
36 nopper aJ Horii Ka Sookdeo-Drost S Wang tH mancini aJ lane at
topical ointment therapy benefits premature infants J Pediatr 1996
128 660ndash669
37 pabst RC Starr Kp Qaiyumi S Schwalbe RS gewold iH the effect
of application of aquaphor on skin condition fluid requirements
and bacterial colonization in very low birth weight infants
J Perinatol 1999 19 278ndash283
38 Kjartansson S Hammarlund K Sedin g insensible water loss from
the skin during phototherapy in term and preterm infants Acta
Paediatr 1992 81 764ndash768
39 grunhagen DJ de Boer mg de Beaufort aJ Walther FJ
transepidermal water loss during halogen spotlight phototherapy in
preterm infants Pediatr Res 2002 51 402ndash405
40 Hanley K Jiand y elias pm Feingold KR Williams ml acceleration
of barrier ontogenesis in vitro through air exposure Pediatr Res
1997 41 293ndash299
41 Denda m Sato J masuda y et al exposure to a dry environment
enhances epidermal permeability barrier function J Invest Dermatol
1998 111 858ndash863
9 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
42 Aringgren J Sjoumlrs g Sedin g ambient humidity influences the rate of
skin barrier maturation in extremely preterm infants J Pediatr 2006
148 613ndash617
43 Sinclair l Sinn J Higher versus lower humidity for the prevention of
morbidity and mortality in preterm infants in incubators (protocol)
Cochrane Database Syst Rev 2007 issue 2 art noCD006472
doi10100214651858
44 Hey en Katz g the optimum thermal environment for naked
babies Arch Dis Child 1970 45 328ndash334
45 Sauer pJJ Dane HJ Visser HKa new standards for neutral thermal
environment of healthy very low birthweight infants in week one of
life Arch Dis Child 1984 59 18ndash22
46 Dollberg S Xi y Donnelly mm a noninvasive alternative to rectal
thermometry for continuous measurement of core temperature in
the piglet Pediatr Res 1993 34 512ndash517
47 messaritakis J anagnostakis D laskari H Katerelos C Rectal-skin
temperature difference in septicaemic newborn infants Arch Dis
Child 1990 65 380ndash382
paeDiatRiCS anD CHilD HealtH 184 16
Practice points
bull Hypothermia in the newborn infant is associated with adverse
outcome
bull Despite improvements in technology the preterm baby is still
at high risk of hypothermia immediately after delivery
bull prevention of evaporative heat losses eliminates hypothermia
at resuscitation
bull High evaporative fluid losses must be prevented if the baby
is nursed under a radiant heater
bull more studies are needed to determine the optimum
management after delivery and to show if reducing
transepidermal water loss has an effect on the rate of skin
maturation
bull Continuous monitoring and display of a central and peripheral
temperature gives early warning of developing cold stress
0 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemiaJ m Hawdon
Abstractat birth the newborn baby undergoes many adaptive changes to inde-
pendent extrauterine life these include the changes of metabolic adap-
tation which must be understood in order to identify and manage the
conditions in which metabolic adaptation is delayed impaired or fails
resulting in low levels of glucose and other metabolic fuels which in turn
affect neonatal neurological function and if prolonged and severe cause
potential adverse outcome Babies identified as at risk of impaired met-
abolic adaptation must undergo clinical monitoring including accurate
blood glucose monitoring tailored to their condition Babies who present
with abnormal clinical signs in association with a low blood glucose level
must be investigated for underlying cause and treated promptly preven-
tion and treatment of clinically significant hypoglycaemia must be planned
to avoid compromising successful establishment of breast feeding
Keywords alternative fuels blood glucose breast feeding neonatal
metabolic adaptation operational thresholds risk factors
Introduction
At birth the newborn baby undergoes many adaptive changes to independent extrauterine life These include the changes of met-abolic adaptation essential to ensure energy provision to vital organs and then to sustain growth and further development The changes involved in metabolic adaptation must be understood in order to identify and manage the conditions in which metabolic adaptation is delayed impaired or fails The clinical outcome of these circumstances is usually referred to with the single short-hand diagnostic term lsquoneonatal hypoglycaemiarsquo However as will be illustrated in this article it is not appropriate to ascribe a diagnostic label to neonatal hypoglycaemia first because glucose is not the only fuel in the neonatersquos fuel economy and second because hypoglycaemia is the consequence of a number of vari-ous underlying disorders and thus does not in itself warrant a diagnostic label
There have been extensive studies of metabolic adaptation in human neonates and neonatal non-human mammals The latter studies have identified those mammals most similar to humans
J M Hawdon MA MBBS MRCP FRCPCH PhD is Consultant Neonatologist and
Honorary Senior Lecturer at UCL EGA Institute for Womenrsquos Health
Elizabeth Garrett Anderson and Obstetric Hospital University College
London Hospitals NHS Foundation Trust Huntley Street London UK
paeDiatRiCS anD CHilD HealtH 184 161
in terms of metabolic adaptation and sought to compare nutri-tionally comparable time frames eg suckling versus weaning periods Whilst the processes of metabolic adaptation are well described in term and preterm human neonates there are few if any clinical studies in human neonates of sufficient rigour to provide evidence for the circumstances in which brain injury may occur and thus it is not possible to provide evidence-based guide-lines for the prevention and management of clinically significant hypoglycaemia Therefore recommendations in this article and in the referenced review articles by recognized experts remain pragmatic and urge clinicians to individualize management for each baby placing heavy emphasis on careful clinical evaluation rather than single numerical definitions of brain-injuring hypogly-caemia and on detecting and treating underlying pathologies1ndash6
Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
During intrauterine life the fetus receives via the placenta a con-stant supply of nutrients initially for growth but in the third tri-mester also for storage Glucose crosses the healthy placenta at a rate of approximately 5 mgkgmin In addition to that required for basal fetal metabolism glucose is converted to glycogen which is stored in the liver cardiac muscle and central nervous system In the third trimester excess glucose is converted to tri-glycerides which are stored in adipose tissue
Insulin is an important fetal hormone to ensure glucose and other substrates are utilized for growth and storage but in nor-mal circumstances insulin is not required for fetal glucose con-trol The exception is for the infant of the mother with poorly controlled diabetes when transfer of glucose across the placenta is at a higher rate driven by the maternalndashfetal concentration gra-dient This results in increased insulin secretion excess growth and increased storage of glycogen and adipose tissue (macroso-mia) along with increased risk of intracellular hypoxia
Conversely in the fetus affected by severe placental insuffi-ciency transfer of glucose and other nutrients across the placenta is at a lower rate and the fetus is required to metabolize first its own fuel stores and then structural proteins (eg in muscle) to ensure energy delivery to the vital organs assisted by the redis-tribution of blood flow to these organs Should placental function deteriorate further these adaptive responses fail Fetal hypogly-caemia has been described in these circumstances78
When placental nutrition abruptly ceases at birth the healthy neonate is dependent upon endocrine changes to initiate meta-bolic adaptation Insulin levels fall steadily and the action of any residual circulating insulin is overcome by the surge of the coun-ter-regulatory hormones glucagon and the catecholamines This change in the balance of glucoregulatory hormones induces the activity of key enzymes for glycogenolysis (release of glucose from glycogen stores) gluconeogenesis (production of glucose from precursors including glycerol and amino acids) lipolysis (release of free fatty acids and glycerol from adipose tissue stores) and beta-oxidation of fatty acids to produce ketone bodies910 If fasting is prolonged structural protein is broken down to release gluconeogenic amino acids Other than lipolysis and proteolysis all of these processes take place in the liver Glycogenolysis also takes place in cardiac muscle and the central nervous system providing immediate energy (in the form of glucose or lactate)
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
at this crucial time411 Clearly during this catabolic phase of immediate postnatal nutrition prior to the establishment of suck-ling feeds provision of energy for vital organ function is at the expense of growth and fuel storage
The postnatal metabolic transition is characterized by low cir-culating blood glucose concentrations compared to those of older infants and children often for a number of days12 This is almost always of no pathological significance for a number of reasons including differences in the function and metabolic requirements of the brain and importantly the production and utilization of alter-native fuels lactate and ketone bodies which are in plentiful supply in the neonate341213ndash20 An important finding from clinical studies and of clinical relevance to those caring for mothers and babies is that in all groups of infants studied to date those who are breast fed have higher circulating ketone body levels than those who are formula fed even after correcting for blood glucose levels102122
There are circumstances however when hypoglycaemia is severe and prolonged and conditions when alternative fuel pro-duction is also impaired or fails In these circumstances low blood glucose levels do acquire clinical significance The key metabolic processes and the risk factors for impaired metabolic adaptation are summarized in Table 1
Metabolic changes at birth ndash key hormones and metabolic processes and risk factors for impaired metabolic adaptation
Postnatal metabolic
changes
Risk factors
Hormones
insulin falls neonatal hyperinsulinism ndash infant of
diabetic mother or idiopathic
glucagon surge possibly blunted by iv glucose or
formula feeds
Catecholamine surge maternal beta-blocker medication
(Cortisol ndash weak effect) (pituitary or adrenal insufficiency)
Metabolic processes
glygogenolysis preterm intrauterine growth
restriction (iugR) ndash reduced stores
perinatal hypoxia-ischaemia ndash stores
utilized
Hyperinsulinism
maternal beta-blocker medication
glycogen storage disorders
gluconeogenesis Hyperinsulinism
maternal beta-blocker medication
Hepatic dysfunction
Very rare inborn errors of metabolism
lipolysis preterm iugR ndash reduced stores
Hyperinsulinism
maternal beta-blocker medication
Ketogenesis Defects of beta-oxidation of fatty
acids
Hepatic dysfunction
Table 1
paeDiatRiCS anD CHilD HealtH 184 16
Impaired metabolic adaptation
Risk factors for impaired metabolic adaptation vary and may be related to any of the following reduced body fuel stores failure of the normal endocrine changes at birth systemic illnesses which impede function of the liver where the key metabolic processes occur or rarely inborn errors of metabolism (see Table 1)
It is well recognized that significant hypoglycaemia will result in a reduced level of consciousness andor fits However it is always important to be alert for detect and treat an underlying pathology which could be causing both the hypoglycaemia and the abnormal signs Often abnormal signs and hypoglycaemia are co-morbidities eg a primary neurological problem causes both abnormal neurological signs and hypoglycaemia secondary to poor feeding For this reason all possible underlying causes for presentation with hypoglycaemia must be considered and investigations planned accordingly Investigations for inborn errors of metabolism and endocrine disorders are most informa-tive if carried out when blood glucose levels are low
There have been extensive efforts to use data from clinical stud-ies of the human neonate to determine the significance of neonatal hypoglycaemia in terms of neurophysiological neurodevelopmental and neuroradiological sequelae However there are major difficul-ties in interpreting these clinical studies as to date these have been flawed by confounding factors such as immaturity placental insuf-ficiency and co-existing complications by heterogeneity of subjects and by failure to take into account protective mechanisms11423 The evidence from both animal and human studies suggests lsquopurersquo hypo-glycaemic brain injury is rare and for hypoglycaemic brain injury to occur there must be co-existing failure of metabolic adaptation such that alternative fuels are not available There is no evidence that lsquotransitionalrsquo hypoglycaemia in the healthy neonate is associated with acute or long term sequelae and indeed even for babies in the at-risk groups on many occasions protective factors will prevail
Diagnosis of clinically significant hypoglycaemia
lsquoNeonatal hypoglycaemiarsquo is a commonly cited diagnosis most often based on a single blood glucose level and using inaccurate methods of measurement and with disregard for the presence or absence of associated clinical signs In the many published texts and local guidelines there is no consistency of approach For this reason a multinational group of experts attempted to examine critically the evidence on which clinical recommendations should be made1 Fol-lowing detailed analysis the authors considered it impossible to define hypoglycaemia as a single blood glucose level and instead suggested operational thresholds and therapeutic goals They con-cluded that low blood glucose levels accompanied by neurological signs should be investigated and treated regardless of the blood glu-cose level They also pragmatically concluded that a blood glucose level below 10 mmollitre should be treated immediately In babies who are at risk of impaired metabolic adaptation but who have no clinical signs it is recommended that interventions to raise blood glucose level are considered if blood glucose levels are persistently below 20 mmollitre For sick and very low birthweight babies who are likely to have a requirement for intravenous glucose there should be a lsquotherapeutic goalrsquo to maintain blood glucose levels above 25 mmollitre Where there is known hyperinsulinism (a very high-risk condition characterized by high intravenous glucose
2 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
requirements to maintain normoglycaemia) an operational thresh-old and therapeutic goal of 35 mmollitre has been proposed24
Finally there must be careful consideration of the infant of the diabetic mother In extreme and rare cases there may be signifi-cant but transient hyperinsulinism and in these cases the thera-peutic goal must be 35 mmollitre More commonly babies whose mothersrsquo diabetes has been well controlled will have normal lsquotran-sitional hypoglycaemiarsquo or slightly delayed metabolic adaptation while insulin levels fall postnatally There must be careful and repeated clinical assessment including blood glucose monitoring For infants of diabetic mothers who have no evidence of signifi-cant hyperinsulinism and no abnormal clinical signs there is no evidence that the operational threshold for hyperinsulinism must be applied Indeed to do so would result in separation of large numbers of healthy babies from their mothers with the conse-quent impact upon breast feeding and resource allocation25
The operational thresholds for various groups of babies are summarized in Table 2
The guidance relating to operational thresholds is predicated upon the accurate measurement of blood glucose levels It is now well known that the commonly used reagent strips are insufficiently accurate to diagnose hypoglycaemia and monitor at-risk infants and there must be access to equipment which allows immediate and accurate determination of blood glucose levels1426ndash28
Blood glucose monitoring
An accurate method for blood glucose monitoring must be employed as described above The sample should be free flowing venous or from a warm heel such that the blood flows freely without squeezing
Blood of high haematocrit often yields low blood glucose lev-els because of dilution of glucose by red cell water However this is also clinically relevant because polycythaemia is itself a high-risk situation Therefore in polycythaemic infants both the haematocrit and blood glucose level must be monitored and both acted upon accordingly
Operational thresholds for blood glucose levels in the management of babies at risk of impaired metabolic adaptation124
Clinical condition Blood glucose level at which
to consider intervention and
therapeutic goal
all at-risk babies lt10 mmollitre
abnormal neurological
signs
intervene regardless of blood
glucose levelSystematically unwell baby therapeutic goal of 25 mmollitre
at-risk babies no abnormal
neurological signs
persistently lt20 mmollitre
Hyperinsulinism 35 mmollitre
Table 2
paeDiatRiCS anD CHilD HealtH 184 163
Only babies in at-risk groups or babies who have abnormal neurological signs should be subjected to blood glucose monitor-ing (Table 3)
It is important not to commence blood glucose monitoring too soon after birth as to do so would fail to differentiate the baby with incipient hypoglycaemia from the baby undergoing the nor-mal postnatal fall in blood glucose level It is recommended in the otherwise healthy but at-risk baby to wait until around 3 h after birth to make the first blood glucose estimation2528 In prac-tice this is usually before the second feed assuming best practice of offering a baby a breast (or if necessary formula feed) imme-diately after birth Clearly if the baby is unwell or has abnormal clinical signs in the first 3 h they will be treated according to clinical condition which will include intravenous fluids and the therapeutic goal described above would apply
Similarly the temptation to measure blood glucose level shortly (within 2 h) after intravenous glucose has been discon-tinued must be avoided In this circumstance as at birth blood glucose levels fall and then subsequently rise in response to coun-ter-regulation It is this effective rise which must be assessed by blood glucose measurement at least 2 h after a change is made (provided the baby remains clinically well)
Blood glucose levels rise after a feed and fall to a nadir before the subsequent feed As our concern is the lowest blood glucose level during the feed cycle and as this measurement may assist in determining best feed frequency it is important that pre-feed blood glucose concentration is measured There is no clinical value in measuring a post-feed blood glucose level as this may be falsely reassuring and this practice subjects babies to more frequent heel pricks or venesections than is necessary
Finally consideration must be given to when to discontinue blood glucose monitoring This will depend upon the babyrsquos clin-ical condition feeding pattern and underlying disorder or risk factors for impaired metabolic adaptation
Prevention and management of clinically significant hypoglycaemia
In babies at risk of clinically significant hypoglycaemia and who are well enough to tolerate enteral feeds milk feeds are the
At-risk babies for whom blood glucose monitoring is recommended
abnormal neurological signs
Systemically unwell eg suspected or proven infection
hypoxicndashischaemic encephalopathy
preterm (lt 37 weeks)
intrauterine growth restriction (lt 2nd centile and any baby with
signs of wasting)
infant of diabetic mother
polycythaemia
maternal beta-blocker medication
Suspected hyperinsulinism
Suspected inborn error of metabolism or endocrine disorder
Table 3
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
mainstay of prevention For babies who are able to feed orally breast feeding should be first choice and there must be maximal support for the mother to do so This is a key clinical priority for midwives and paediatricians
If there are concerns regarding adequacy of breast feeding to prevent hypoglycaemia the mother should be encouraged to commence expression of milk from very soon after birth If there is insufficient breast milk to prevent babies reaching the opera-tional thresholds described above there should be judicious use of formula milk using only the smallest amount required to keep the babyrsquos glucose in the required range Formula milk in exces-sive quantities has been demonstrated to suppress normal meta-bolic adaptation2122
In babies for whom early enteral feeds are not appropriate or not tolerated or for whom enteral feeding does not prevent blood glucose level falling below operational thresholds intravenous glucose infusion at rates around 4ndash5 mgkgmin (58ndash72 mlkgd of 10 dextrose) are usually sufficient to prevent hypoglycae-mia If blood glucose levels remain below therapeutic goals the rate of infusion may be steadily increased Excess glucose infu-sion over and above that required to maintain the therapeutic goal will stimulate insulin and there is a risk of rebound hypo-glycaemia if high rate glucose infusions are too rapidly reduced Milk feeds if tolerated should be continued if intravenous glu-cose is commenced
If infused volume of glucose solution becomes excessive in order to maintain therapeutic goals or if fluid restriction must be applied more concentrated glucose concentrations must be infused through a central venous line This is particularly rel-evant to the hyperinsulinaemic baby in whom glucose infusion rates in excess of 8ndash10 mgkgmin are required to maintain ther-apeutic goals There is a high risk of severe and brain-damaging hypoglycaemia if treatment is delayed or fails to raise blood glu-cose levels and management of these babies requires consulta-tion with or referral to a specialist centre24
If there is presentation of hypoglycaemia with abnormal clinical signs or a very low blood glucose level (less than 1 mmollitre) this mandates urgent treatment with intravenous glucose The rates of glucose infusion described above are usually sufficient to bring the blood glucose level rapidly to the therapeutic goal without a bolus of glucose being necessary In fact a bolus dose of glucose will result in a peak blood glucose level and then an insulin surge making subsequent management problematical This is minimized by the use of a lsquomini-bolusrsquo should a bolus of glucose be required ndash 200 mg glucosekg (2 mlkg of 10 dextrose)28 Indications for mini-bolus are infants presenting with fits or coma or an lsquounre-cordablersquo or zero blood glucose level A mini-bolus should always be followed with glucose infusion or an increased glucose infusion rate if a baby already receiving intravenous glucose has required a mini-bolus
The temptation to supplement enteral feeds with glucose polymers and energy supplements (eg Duocal) or to use oral glucose gels or solutions (eg Hypostop) should be avoided as this carries a risk of necrotizing enterocolitis is likely to suppress normal metabolic adaptation and will suppress the appetite of the baby for effective oral feeding
Finally there are additional medications which may be employed in specific circumstances (Table 4) More detailed descriptions are given elsewhere242728 Babies who have hypoglycaemia which
paeDiatRiCS anD CHilD HealtH 184 164
is difficult to control by the measures described above and who require these additional treatments should be cared for in a centre which has expertise in metabolic and endocrinological conditions
Summary
Much controversy and confusion has surrounded neonatal hypo-glycaemia but this usually arises as a result of failure to under-stand the processes of normal metabolic adaptation and the fact that hypoglycaemia is a presenting sign rather than a diagnosis in itself Plans for investigation and management must be based upon the most likely underlying cause of impaired metabolic adaptation and take into account the clinical condition of the baby This is counter to the current trend to propose rigid pro-tocols and algorithms and re-introduces the value of detailed clinical evaluation and decision making The mainstay of man-agement is close clinical observation of vulnerable infants and energy provision tailored to their individual needs whilst avoid-ing excessively invasive management (namely unnecessary sep-aration of mother and baby routine or excessive formula milk supplementation or intravenous glucose administration) which themselves inhibit protective metabolic responses and impede successful establishment of breast feeding
ReFeRenCeS
1 Cornblath m Hawdon Jm Williams aF et al Controversies regarding
definition of neonatal hypoglycemia Suggested operational
thresholds Pediatrics 2000 105 1141ndash1145
2 Cornblath m ichord R Hypoglycemia in the neonate Semin
Perinatol 2000 24 136ndash149
3 Vannucci RC Vannucci SJ Hypoglycaemic brain injury Semin
Neonatol 2001 6 147ndash155
4 Rozance pJ Hay WW Hypoglycaemia in newborn infants features
associated with adverse outcomes Biol Neonate 2006 90 74ndash86
5 Hawdon Jm Hypoglycaemia in newborn infants defining the
features associated with adverse outcomes ndash a challenging remit
Biol Neonate 2006 90 87ndash88
6 Williams aF neonatal hypoglycaemia clinical and legal aspects
Semin Fetal Neonatal Med 2005 10 363ndash368
7 Soothill pW nicolaides KH Campbell S prenatal asphyxia
hyperlacticaemia hypoglycaemia and erythroblastosis in growth
retarded fetuses BMJ 1987 294 1051ndash1053
Additional medication in specific conditions (if these are required there must also be referral to a specialist centre)
Medication Indication
glucagon intramuscular bolus dose of 200 μgkg
transient rise in blood glucose level eg
when difficulty re-siting intravenous infusion
Diazoxide Hyperinsulinism
Hydorcortisone pituitary or adrenal insufficiency
Table 4
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
8 Hawdon Jm Ward platt mp mcphail S Cameron H Walkinshaw Sa
prediction of impaired metabolic adaptation by antenatal Doppler
studies in small for gestational age fetuses Arch Dis Child 1992
67 787ndash792
9 Deshpande S Hawdon Jm et al adaptation to extrauterine life in
Rodeck C Whittle m eds Fetal medicine Basic Science and Clinical
practice edinburgh Churchill livingstone 1999
10 Ward platt m Deshpande S metabolic adaptation at birth Semin
Fetal Neonatal Med 2005 10 341ndash350
11 eyre Ja Stuart ag Forsyth RJ Heaviside D Bartlett K glucose
export from the brain in man evidence for a role for astrocytic
glycogen as a reservoir of glucose for neural metabolism Brain Res
1994 28 349ndash352
12 Hawdon Jm Ward platt mp aynsley-green a patterns of metabolic
adaptation for preterm and term infants in the first neonatal week
Arch Dis Child 1992 67 357ndash365
13 Hawdon Jm Ward platt mp aynsley-green a prevention and
management of neonatal hypoglycaemia Arch Dis Child Fetal
Neonatal Ed 1994 70 F60ndash64
14 Hawdon Jm Hypoglycaemia and the neonatal brain Eur J Paediatr
1999 158 S9ndash12
15 massieu l Haces ml montiel t Hernaacutendez-Fonseca K acetoacetate
protects hippocampal neurons against glutamate-mediated neuronal
damage during glycolysis inhibition Neuroscience 2003 120
365ndash378
16 yamada Ka Rensing n thio ll Ketogenic diet reduces
hypoglycaemia-induced neuronal death in young rats Neurosci Lett
2005 385 210ndash214
17 nehlig a Brain uptake and metabolism of ketone bodies in animal
models Prostaglandins Leukot Essent Fatty Acids 2004 70
265ndash275
18 Hernaacutendez mJ Vannucci RC Salcedo a Brennan RW Cerebral blood
flow and metabolism during hypoglycemia in newborn dogs
J Neurochem 1980 35 622ndash628
19 Vannucci RC nardis ee Vannucci SJ Campbell pa Cerebral
carbohydrate and energy metabolism during hypoglycaemia in
newborn dogs Am J Physiol 1981 256 H1659ndashH1666
20 anwar m Vannucci RC autoradiographic determination of regional
cerebral blood flow during hypoglycaemia in newborn dogs Pediatr
Res 1988 24 41ndash45
21 Hawdon Jm Williams aF et al Formula supplements given to
healthy breastfed preterm babies inhibit postnatal metabolic
adaptation results of a randomised controlled trial Arch Dis Child
2000 82 a30
paeDiatRiCS anD CHilD HealtH 184 16
22 de Rooy l Hawdon Jm nutritional factors that affect the postnatal
metabolic adaptation of full-term small- and large-for gestational
age infants Pediatrics 2002 109 e42
23 Hawdon Jm Hypoglycaemia and brain injury ndash when neonatal
metabolic adaptation fails in levene m ed Fetal and neonatal
neurology and neurosurgery edinburgh Churchill livingstone in
press
24 Hussain K Congenital hyperinsulinism Semin Fetal Neonatal Med
2005 10 369ndash376
25 acolet D Diabetes in pregnancy Caring for the Baby after Birth
CemaCH 2007 2
26 Hussain K Sharief n the inaccuracy of venous and capillary blood
glucose measurement using reagent strips in the newborn period
and the effect of haematocrit Early Hum Dev 2000 57 111ndash121
27 Hawdon Jm Disorders of blood glucose homeostasis in the neonate
in Rennie Jm ed Robertonrsquos textbook of neonatology 4th edn
edinburgh Churchill livingstone 2005
28 Deshpande S Ward platt mp the investigation and management
of neonatal hypoglycaemia Semin Fetal Neonatal Med 2005 10
351ndash361
Practice points
bull identify risk factors for impaired metabolic adaptation
bull Clinical monitoring including accurate blood glucose
measurement for at-risk babies
bull Feed at-risk babies soon after birth and maintain thermal
homeostasis
bull take first blood glucose level at 3ndash4 h of age
bull intervene in at-risk baby with no clinical signs if two
consecutive blood glucose measurements lt 20 mmollitre
bull intervene in any baby with blood glucose measurement
lt 10 mmollitre
bull intervene in any baby with abnormal clinical signs regardless
of blood glucose level
bull investigate for underlying cause of failure of metabolic
adaptation
bull maintain lactation and breast feeding
5 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Resuscitation of the term and premature babyJonathan Wyllie
Abstractalthough most newly born babies establish normal respiration and
circulation without help up to 1minus2 may require some resuscitation
or stabilization Babies who do not establish adequate regular normal
breathing or who have a heart rate of less than 100 beatsmin or other
problems such as prematurity may require assistance the differences in
approach to the resuscitation of such babies originate in the physiology
and pathophysiology of acute asphyxia at birth However management
of airway and breathing remain the key features of resuscitation and
where cardiac depression has occurred this is nearly always due to hy-
poxia secondary to respiratory compromise therefore most babies will
respond within 2minus3 min of effective aeration of the lungs and the need
for intubation chest compressions or drugs is rare the international
liaison Committee on Resuscitation (ilCoR) evaluated evidence in 2000
and 2005 in order to provide guidelines for resuscitation they will do
so again for 2010 this evidence is limited in terms of both quantity and
quality and controversies still exist more research is needed to ensure
that our future actions are based upon evidence rather than history this
article will review the recommended approach to resuscitation as well as
some newer evidence
Keywords guidelines neonatal newborn premature resuscitation
Background
In the UK 669 601 babies were born alive in 2006 and most made the transition to extrauterine life without problems Those babies who did not establish adequate regular normal breathing or who had a heart rate of less than 100 beatsmin may have required assistance1 Factual evidence concerning the true requirement for resuscitation at birth is sparse Up to 10 of newborns may require some assistance to begin breathing with less than 1 needing extensive resuscitation2 However just because a baby received resuscitation does not necessarily mean that it was required and rates of intervention may be altered by educa-tion34 or the personnel present at deliveries5 In a UK tertiary centre with a standard approach to resuscitation at birth up to 12 of all babies received some airway assistance with just over 1 being intubated3 In Sweden only 1 of babies over 2500 g required mask or endotracheal tube ventilation at birth of which most responded to the former4
Jonathan Wyllie MBChB FRCPCH is Consultant Neonatologist at the James
Cook University Hospital Marton Road Middlesbrough TS4 3BW UK
paeDiatRiCS anD CHilD HealtH 184 16
Sometimes it is possible to predict babies who are likely to have respiratory depression at birth and to have appropriate per-sonnel present at delivery Guidelines for attendance at deliveries will vary with institution but even when almost 40 of deliv-eries are attended there may still be a further 15 of babies who require unexpected resuscitation5 a proportion that seems to remain whatever changes are made
The physiology of babies requiring help at birth has been summarized previously167 It allows a logical approach to resus-citation (Figure 1) when evidence is lacking and may prompt further research
Resuscitation at birth
PreparationAt birth resuscitation is more likely in babies with intrapartum evidence of significant fetal compromise those less than 35 weeksrsquo gestation those delivering vaginally by the breech and in multiple births Personnel trained in newborn resuscitation should be available at every delivery1 Someone experienced in tracheal intubation and advanced resuscitation should also be easily available for normal low-risk deliveries in hospital and ideally in attendance for deliveries with an increased likelihood of needing resuscitation In the latter cases the equipment and environment can be prepared beforehand including a discussion with the parents Wash your hands put on gloves and consider what help may be needed
Cord clampingAt birth it has long been known that delay in clamping the cord will lead to less anaemia in babies and reduce subsequent iron deficiency8 However few hospitals have practised this interven-tion due to worries about hypothermia and the need to resusci-tate or stabilize babies In developed countries the advantages seemed to be outweighed by the potential disadvantages A recent randomized controlled study of delayed clamping of the cord in premature babies found that the intervention group had less late-onset sepsis and fewer intraventricular haemorrhages9 This is a low-risk strategy which needs further evaluation in order to introduce it without increasing other risk factors in pre-mature deliveries
Assessment and temperature controlAssessment and temperature control for the newborn baby should occur at all deliveries The assessment indicates the need for resuscitation Babies may vary from 23 to 40+ weeksrsquo ges-tation and in weight from 500 to 5000 g They are born naked and wet and if left cannot cope with an environmental tem-perature of less than 32degC However if the term baby is imme-diately dried put skin-to-skin with the mother and covered the delivery room temperature can be as low as 25ndash28degC Obviously the smaller the baby the greater the surface area to mass ratio and the greater the risk of hypothermia Compromised babies are particularly vulnerable10 and hypothermia will lower oxygen tension11 increase metabolic acidosis12 and inhibit surfactant production13
An effective method of maintaining the temperature of prema-ture babies less than 28 weeksrsquo gestation is wrapping them with plastic before drying and then placing them under a radiant
6 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Dry the babyRemove any wet towels and cover
Start the clock or note the time
Give 5 inflation breathsLook for a response
If no increase in heart rate look for chest movement
Re-check head positionApply Jaw thrust
Repeat inflation breathsLook for a response
If no increase in heart rate look for chest movement
Try alternative airway opening manoeuvresRepeat inflation breaths
Look for a response
If no increase in heart rate look for chest movement
If the heart rate is not detectable or slow (lt60)Start compressions
3 compressions to each breath
Reassess heart rate every 30 secondsConsider venous access and drugs
Assess colour tone breathing and heart rate
Open the airway
If not breathing
If still not breathing
If no response
If still no response
When the chest is moving
If meconium present
Baby breathing wellDo not suction the airway
Baby floppy and not breathing wellConsider inspection and suction before
inflation breaths
Head in neutral position
Inflation breathsUse a well-fitting face mask
connedted to a
pressure-limited gas supply
Each breath 2ndash3 seconds
duration at 30 cm H2O for a
term baby
Get help from a second personto support the airway andor
inspect the oropharynx under
direct vision and consider
suction andor insert an
oropharyngeal airway
Chest compressionsCompvent ratio 31
Rate 120 events per minute
Ensure the chest moves with each ventilation breath
If breathingReassess heart rate and monitor baby
If heart rate is satisfactory but increasingContinue ventilation breaths at about 30 per
minute until baby is breathing adequately
If heart rate is satisfactory but increasingContinue ventilation breaths at about 30 per
minute until baby is breathing adequately
If heart rate is increasingStop compressions
Continue ventilation breaths at about 30 per
minute until baby is breathing adequately
If the chest is not movingRecheck head position and repeat inflation
breaths If competent consider intubation
If the chest is still not movingThe airway is the problem
Figure 1 newborn life support (Courtesy of the Resuscitation Council uK)
heater14 There is a small risk of hyperthermia so the temperature must be monitored carefully
An assessment is made of the babyrsquos colour tone respira-tions and heart rate127 The most important of these is heart rate and a stethoscope is more reliable than cord pulsation15 How-ever saturation monitors may offer a more reliable assessment of both heart rate and colour16 but their interpretation requires a detailed knowledge of normal saturations at birth at differing gestations A baby who is apnoeic and floppy in the absence of neurological disease is unconscious and likely to be in terminal apnoea however this does not change the initial approach other
paeDiatRiCS anD CHilD HealtH 184 167
than the need to summon help early APGAR scores are never calculated to guide resuscitation
Airway
If a baby is in primary apnoea then with an open airway the first gasp will start to aerate the lungs and most babies will be able to lsquoresuscitatersquo themselves as shown in physiological stud-ies on animals Neutral positioning of the babyrsquos head chin lift jaw thrust oropharyngeal airways and endotracheal intubation may all be helpful in certain situations if performed correctly17
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Endotracheal intubationThe placement of an endotracheal tube has long been the gold standard of airway control and this remains true in the unconscious baby if it is correctly sized placed and fixed in a timely manner However experience is directly related to effec-tiveness in endotracheal intubation1819 and the success rate of less experienced clinicians such as a resident (STA1-3) or a fel-low (STA3-5) is lower varying between 33 and 68 Even senior neonatologists often take longer than guidelines recom-mend19 Experienced clinicians may judge correct endotracheal position visually or by an increase in heart rate with the first breaths but detection of exhaled carbon dioxide will give more rapid confirmation in larger babies12171920 and this can be par-ticularly useful for less experienced clinicians or those supervis-ing them However not all systems for the detection of exhaled carbon dioxide work in the smallest premature infants
Laryngeal masksLaryngeal masks may be effective for ventilating term newborn babies but there are few data for small premature infants There have been reports of dislodged laryngeal airways during paedi-atric arrests when chest compressions have been administered Although success of placement at first attempt by paediatri-cians is greater with a laryngeal mask than with an endotra-cheal tube21 the only and small randomized controlled trial in the delivery room favoured endotracheal intubation when per-formed by an anaesthetist22 Based mainly upon case reports the laryngeal mask can be recommended when positioning and mask ventilation and endotracheal intubation have failed to secure the airway but not as yet as a primary method of airway control
MeconiumIn 2000 Wisewell et al23 reported a large randomized controlled trial showing that tracheal intubation and suctioning of meco-nium-stained but vigorous babies at birth did not reduce the incidence or severity of meconium aspiration syndrome More recently another randomized trial has now shown that suction-ing on the perineum similarly offers no benefit24 Neither of these practices is recommended but intubation and suction of meconium from the trachea of non-vigorous babies born through meconium-stained liquor is still recommended
Breathing
In the apnoeic baby the first breaths establish the resting lung volume and aerate the fluid-filled alveoli This mechanical effect aided by surface tension within the alveoli causes the initial fall in pulmonary vascular resistance Experimentally this effect occurs even if the lungs are ventilated with nitrogen but is increased when air is used presumably due to the vasodilator effect of 21 oxygen The mechanical stretching of the lung also triggers the activation of cyclo-oxygenase beginning the production of prostacyclin Bradykinin is produced which has a further direct vasodilator effect and also possibly via prostacyclin Therefore adequate airway control and passive ventilation is vital not only because babies requiring resuscitation at birth have an almost uniformly respiratory aetiology but also in order to promote post-natal adaptation and reverse any maladaptation
paeDiatRiCS anD CHilD HealtH 184 16
In term babies peak ventilatory pressures of 20ndash30 cmH2O may be required but the minimal pressure needed to achieve an improvement in heart rate should be used or if there is no response chest wall movement Longer breaths at lower pressure may be more effective in displacing alveolar fluid and establish-ing the resting lung volume in lungs with sufficient surfactant and may improve initial oxygenation However premature new-borns are obviously physiologically and anatomically less pre-pared for delivery than infants at term Over-inflation has been implicated in histological lung damage in animal models and high tidal volumes appear to be equally damaging whether given before or immediately after administration of surfactant How-ever the same effect is not seen if these excessive tidal volumes are delivered 15 min after administration of surfactant2526 It is now thought that both excess end expiratory volume and inad-equate end-expiratory volume may cause lung damage2728 In premature infants it would therefore seem sensible to use lower pressures of 20ndash25 cmH2O12 delivered in a controlled way to prevent over-inflation and to apply positive end-expiratory pres-sure (PEEP) to prevent damage from under-inflation PEEP also improves both lung compliance and gas exchange2930 Without PEEP the airways collapse during the expiratory phase in animal models of newborn resuscitation
If animal data can be extrapolated it would also seem appro-priate to give surfactant as soon as possible to premature babies in order to ameliorate damage2526
The majority of newborn infants requiring resuscitation will re-establish regular respiration after administration of a few breaths which may be due to Headrsquos paradoxical reflex by which the inflation triggers an inspiratory effort
VentilationOnce the lungs are aerated if the newborn remains apnoeic ventilation should be continued at 30ndash60 breathsmin avoiding hyperventilation and using the minimum pressure possible to maintain a heart rate greater than 100 beatsmin
Face mask the majority of infants who require ventilation receive it via a face mask This may be attached to a bagvalve system with a spring lsquoblow offrsquo system or a lsquoT-piecersquo with a set flow and pressure It is important to realize that the bagvalve system is flow sensitive and that the harder the operator presses the greater the flow and the higher the delivered pressure In fact 60 cmH2O can be achieved with vigorous squeezing of a self-inflating bag Therefore it may be advantageous that most opera-tors are unlikely to be as effective as they suppose in creating a seal with the mask31 This is a skill that requires tuition and prac-tice31 In delivering a set pressure T-piece systems such as the Tom Thumbcopy or Neopuffcopy perform better than any bagminusvalve system but require a gas supply There is no evidence that lung compliance can be assessed using any bag system
Continuous airway pressure case series have suggested that early or delivery room use of continuous positive airway pres-sure (CPAP) in premature babies may reduce chronic lung dis-ease There have been two randomized trials of which one was a pilot study The data from the COIN trial do not show any advan-tage other than a reduction in intubation and surfactant use in the intervention group However an excess of pneumothorax
8 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
was also reported The Vermont Oxford Network and the SUP-PORT trials will provide further data but at present the delivery room use of CPAP cannot be widely recommended and should be limited to those units experienced in its use or taking part in research
Air or oxygen oxygen has been in widespread use for resuscita-tion at birth since the 1930s and even hyperbaric oxygen was seriously supported in the 1960s For many years there have been concerns about tissue damage from oxygen deprivation during and after resuscitation It became evident in the 1950s that unrestricted oxygen therapy could have serious conse-quences for future vision More recently concerns have been raised about potential adverse effects on respiratory physiology cerebral circulation and tissue damage from oxygen free radicals even during resuscitation A meta-analysis of four human studies demonstrated a reduction in mortality and no evidence of harm in infants resuscitated in air versus 100 oxygen3233 However there are several significant methodological concerns with these studies and the results should be interpreted with caution There is insufficient evidence to recommend any specific concentration of oxygen to be used for newborn resuscitation Monitoring the oxygen saturation of babies may be helpful but as yet there are no time-related normal target ranges and healthy term babies may take up to 10 min to achieve preductal oxygen saturation of greater than 95 and up to 60 min to achieve this postductally
There is therefore equipoise which would be open to an appropriate randomized controlled trial In the meantime the evidence only supports use of either 21 or 100 oxygen It is provoking to realize that if air had been in constant use since the 1930s there would be insufficient evidence for use of supple-mental oxygen
Circulation
Early resuscitation (temperature control airway breathing) provides oxygenated blood in the pulmonary arterioles which if returned to the heart causes the rate to increase34 If due to acidosis and hypoxia the circulation is ineffective then chest compressions may be needed They should be commenced when the heart rate remains below 60min despite effective airway and breathing management127 The best technique is using two hands to encircle the chest1 A ratio of three compressions to one breath is internationally accepted127 but has no evidence to support it Research has shown that neither compressions nor drugs will work in this situation without oxygenated blood so effective lung aeration and ventilation is essential A logical approach would be to fill the alveoli with air and to compress the chest until they are empty However training and teamwork require an agreed ratio which has therefore not changed since guidelines were first agreed internationally Success is assessed by an increase in heart rate which should therefore be assessed every 30 s Compressions stop when the spontaneous heart rate is greater than 60 beatsmin
In hypoxic newborn animal models successful resuscitation can restore cardiac output and blood pressure to levels above baseline within 5ndash10 min However it should be noted that there is a decline to 30 lower than basal levels within 2 h and that blood pressure is relatively spared suggesting an even greater
paeDiatRiCS anD CHilD HealtH 184 16
reduction in tissue perfusion This should be considered in the later care of any neonate who was hypoxic at birth
Drugs
Neonatal bradycardia at birth is almost always due to hypoxia plusmn acidosis and therefore drugs are rarely needed Adrenaline (epi-nephrine) is reported as being used in between 1 and 4 babies per 2000 births which is a large variation in practice Reported success is also variable and must be interpreted in light of this variation The use of drugs in extremely premature infants is con-troversial Some data suggested good outcomes for babies below 28 weeksrsquo gestation given adrenaline but these were flawed by high numbers of babies receiving resuscitative drugs some before the airway had been appropriately managed Audit data now suggest a poor outcome such that many clinicians would now council against the use of adrenaline and other drugs to resuscitate extremely premature newborn babies
Adrenaline (epinephrine)In 2003 a Cochrane review of randomized controlled trials involv-ing adrenaline use for resuscitation of neonates was unable to identify a single clinical trial35 Despite the lack of human neo-natal data animal models show the potential of adrenaline in asphyxial cardiac arrest and it is reasonable to use it when ade-quate ventilation and chest compressions have failed to increase the heart rate above 60 beatsmin Use 10ndash30 μgkg intrave-nously and preferably via an umbilical venous line The tracheal route cannot be recommended but if used it is likely that doses within this range will be ineffective and 100 μgkg might be tried However the safety of such doses has not been studied
BicarbonateThe use of bicarbonate has long been controversial but many of the concerns relate to the rapid correction of acidosis in neonates after resuscitation or the routine use of bicarbonate infusion nei-ther of which can be advocated There are no published human neonatal data to support its use although some exist from animal studies Animal data have also shown that the binding of adren-aline to receptors in the myocardium is significantly impaired by lactic acidosis and recent work on human lymphocyte beta-adrenergic receptors supports this view Whether this is also true of the more important alpha receptors is unknown In practice reversing intracardiac acidosis may improve myocardial function and assist in achieving a return of spontaneous circulation 1ndash2 mmolkg of bicarbonate may be given but this remains a contro-versial area
VolumeVolume expansion should only be given when it is suspected that the baby has suffered blood loss or the infant appears to be in shock (pale poor perfusion weak pulse) and has not responded adequately to other resuscitative measures If there is no history suggestive of blood loss shock is most likely to be due to myo-cardial dysfunction in which case fluids should be administered cautiously The most logical replacement fluid would be blood but in its absence isotonic crystalloid rather than albumin is the solution of choice given in 10 mlkg aliquots and observing the response Three randomized trials in neonates have shown
9 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
isotonic crystalloid to be as effective as albumin for the treat-ment of hypotension but none has examined either the relative or actual effectiveness in resuscitation A recent blinded randomized study comparing normal saline albumin or no volume expansion in a normovolaemic asphyxiated neonatal animal model showed that volume expansion was not beneficial and made a number of parameters worse36
NaloxoneNaloxone is not recommended as part of the initial resuscita-tion of newborns with respiratory depression Before it is given supporting ventilation should have restored the heart rate and colour The dose is 100 μgkg intravenously or intramuscularly Tracheal administration cannot be recommended Although administration of naloxone to neonates who have been exposed to maternal opioids during labour is a practice of long-standing it lacks the proper evidence of efficacy
Non-response to resuscitation
There are few more frightening situations professionally than applying the correct interventions in resuscitating or stabilizing a baby and getting no response Each stage must be adequately performed before moving onto the next and this requires regular reassessment When experienced help is needed at a newborn resuscitation it is usually the airway and ventilation that require correction If the heart rate does not increase this usually means that the lungs have not been successfully aerated In some cases however it may mean that the heart cannot respond as the cir-culation is inadequate In this situation the only way to check that the lungs have been successfully aerated is to see the chest move with ventilation or to obtain evidence of ventilation from a detector of exhaled carbon dioxide If you do not see chest movement after another five breaths the most likely cause is an obstructed airway either due to incorrect positioning or because the jaw has not been drawn forwards An oropharyngeal airway can be very helpful at this point especially in the term baby Only very occasionally is the airway blocked by mucus vernix blood or meconium but if the airway is guaranteed and there is no heart rate response or chest movement this should be sought by direct suction of the trachea even in the absence of any meconium staining of liquor Pneumothoraces can occur spontaneously after delivery but are rare at resuscitation carried out with pressure-limited devices Equally rare are diaphragmatic hernias that have not been diagnosed antenatally giving problems at resuscitation
If the chest is moving but the heart rate has not responded to resuscitation consider rare possibilities such as fetal blood loss pneumothorax or heart block (mothers with undiagnosed systemic lupus erythematosis delivered for fetal bradycardia) as possibilities With adequate ventilation there is no evidence of oxygen concentrations less than 100 being responsible for prolonged bradycardia or failure to respond although current practice would support increasing the delivered oxygen concen-tration if resuscitation had been commenced using air
Outcome
The prognosis for the full-term baby subjected to sudden acute asphyxia is usually good provided the episode does not last for
paeDiatRiCS anD CHilD HealtH 184 17
long Most babies resuscitated from primary apnoea have no sequelae secondary to the resuscitation Many babies who start to breathe again regularly within 20 min of the circulation being restored recover completely but it is rare for a baby who is still gasping after 30 min to recover
The prognosis for the preterm baby of less than about 34 weeksrsquo gestation subjected to severe acute anoxia is less predict-able This is because of the risk of secondary intraventricular haemorrhage or periventricular intracerebral haemorrhage andor infarction after even a relatively brief asphyxial episode espe-cially in the period immediately around birth
The effects of chronic hypoxia are also difficult to predict but a reasonably clear idea of the extent of the problem should be obtainable within 36ndash48 h of the original chronic asphyxial insult A mild short-lasting state of hyperexcitability usually car-ries a good prognosis even if there is seizure activity but more severe symptoms can be associated with permanent handicap This is seen especially in infants with encephalopathy requiring ventilation
REFERENCEs
1 Biarent D Bingham R Richmond S et al european Resuscitation
Council guidelines for Resuscitation 2005 Section 6 paediatric life
support Resuscitation 2005 67(suppl 1) S97ndashS133
2 international liaison Committee on Resuscitation part 7 neonatal
resuscitation Resuscitation 2005 67 293ndash303
3 Singh J Santosh S Wyllie J mellon a effects of a course in
neonatal resuscitation - evaluation of an educational intervention
on the standard of neonatal resuscitation Resuscitation 2006 68
385ndash389
4 palme-Kilander C methods of resuscitation in low-apgar-score
newborn infants - a national survey Acta Paediatr 1992 81
739ndash744
5 Kroll l twohey l Daubeney p et al Risk factors at delivery and
the need for skilled resuscitation Eur J Obstet Gynecol Reprod Biol
1994 44 175ndash177
6 Wyllie Jp Resuscitation of the newborn The Foundation Years
2007 3(4) 153ndash157
7 Richmond S ed newborn life Support Resuscitation at Birth
london Resuscitation Council 2006
8 Ceriani Cernadas Jm Carroli g pelligrine l et al the effect of timing
of cord clamping on neonatal venous hematocrit values and clinical
outcome at term a randomized controlled trial Pediatrics 2006
117 e779ndashe786
9 mercer JS Vohr BR mcgrath mm padbury JF Wallach m oh W
Delayed cord clamping in very preterm infants reduces the incidence
of intraventricular hemorrhage and late-onset sepsis a randomized
controlled trial Pediatrics 2006 117 1235ndash1242
10 Dahm lS James lS newborn temperature and calculated heat loss
in the delivery room Pediatrics 1972 49 504ndash513
11 Stephenson J Du J tk o the effect of cooling on blood gas
tensions in newborn infants J Pediatr 1970 76 848ndash852
12 gandy gm adamsons Jr K Cunningham n Silverman Wa James lS
thermal environment and acid-base homeostasis in human infants
during the first few hours of life J Clin Invest 1964 43 751ndash758
13 gluck l Kulovich mV eidelman ai et al Biochemical development
of surface activity in mammalian lung pulmonary lecithin synthesis
0 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
in the human fetus and newborn and etiology of the respiratory
distress syndrome Pediatr Res 1972 6 81ndash99
14 Vohra S Roberts RS Zhang B Janes m Schmidt B Heat loss
prevention (Help) in the delivery room a randomised controlled
trial of polyethylene occlusive skin wrapping in very preterm infants
J Pediatr 2004 145 750ndash753
15 owen CJ Wyllie Jp Determination of heart rate in babies at birth
Resuscitation 2004 60 213ndash217
16 orsquoDonnell Cp Kamlin Co Davis pg Carlin JB morley CJ Clinical
assessment of infant colour at delivery Arch Dis Child Fetal
Neonatal Ed 2007 92 F465ndashF467
17 international liaison Committee on Resuscitation part 13 neonatal
Resuscitation guidelines Circulation 2005 112(suppl 24)
iV188ndashiV195
18 leone ta Rich W Finer nn neonatal intubation Success of
pediatric trainees J Pediatr 2005 146 638ndash641
19 orsquoDonnell Cp Kamlin Co Davis pg morley CJ endotracheal
intubation attempts during neonatal resuscitation success
rates duration and adverse effects Pediatrics 2006 117
e16ndash21
20 Repetto Je Donohue pa-CpK Baker SF Kelly l nogee lm use of
capnography in the delivery room for assessment of endotracheal
tube placement J Perinatol 2001 21 284ndash287
21 gandini D Brimacombe JR neonatal resuscitation with laryngeal
mask airway in normal and low birth weight infants Anesth Analg
1999 89 642ndash643
22 esmail n Saleh m ali a laryngeal mask airway versus endotracheal
intubation for apgar score improvement in neonatal resuscitation
Egypt J Anesthiol 2002 18 115ndash121
23 Wiswell te gannon Cm Jacob J et al Delivery room management
of the apparently vigorous meconium-stained neonate results of
the multicenter international collaborative trial Pediatrics 2000
105 1ndash7
24 Vain ne Szyld eg prudent lm Wisewell te aguilar am Vivas ni
oropharyngeal and nasopharyngeal suctioning of meconium-stained
neonates before delivery of their shoulders multicentre randomised
controlled trial Lancet 2004 364 597ndash602
25 Bjorklund lJ ingimarsson J Curstedt t larsson a Robertson B
Werner o lung recruitment at birth does not improve lung function
in immature lambs receiving surfactant Acta Anaes Scand 2001 45
986ndash993
26 Bjorklund lJ ingimarsson J Curstedt t et al manual ventilation
with a few large breaths at birth compromises the therapeutic effect
of subsequent surfactant replacement in immature lambs Pediatr
Res 1997 42 348ndash355
paeDiatRiCS anD CHilD HealtH 184 17
27 taskar V John J evander e Robertson B Jonson B Surfactant
dysfunction makes lungs vulnerable to repetitive collapse and re-
expansion Am J Respir Crit Care Med 1997 155 313ndash320
28 muscedere Jg mullen JB gan K Slutsky aS tidal ventilation at low
airway pressures can augment lung injury Am J Respir Crit Care Med
1994 149 1327ndash1334
29 nilsson R grossman g Robertson B Bronchiolar epithelial lesions
induced in the premature rabbit neonate by short periods of artificial
ventilation Acta Pathol Microbiol Scand 1980 88 359ndash367
30 probyn me Hooper SB Dargaville pa et al positive end expiratory
pressure during resuscitation of premature lambs rapidly improves
blood gases without adversely affecting arterial pressure Pediatr
Res 2004 56 198ndash204
31 Wood Fe morley CJ Dawson Ja et al improved techniques
reduce face mask leak during simulated neonatal resuscitation
study 2 Arch Dis Child Fetal Neonatal Ed in press doi101136
adc2007117788
32 tan a Schulz a orsquoDonnell CpF Davis pg air versus oxygen for
resuscitation of infants at birth Cochrane Database Syst Rev 2004
(3) CD002273
33 Davis pg tan a orsquoDonnell Cp Schulze a Resuscitation of newborn
infants with 100 oxygen or air a systematic review and meta-
analysis Lancet 2004 364 1329ndash1333
34 Dawes g Fetal and neonatal physiology Chicago year Book
publisher 1968 p 141ndash159
35 Ziino aJa Davies mW Davis pg epinephrine for the resuscitation
of apparently stillborn or extremely bradycardic newborn infants
Cochrane Database Syst Rev 2003 (2) CD003849
36 Wyckoff m garcia D margraf l perlman J laptook a Randomized
trial of volume infusion during resuscitation of asphyxiated neonatal
piglets Pediatr Res 2007 61 415ndash420
Practice points
bull Resuscitation at birth is different from that at all other times
of life
bull a standard approach can be applied to most newborn
resuscitation
bull guidelines are based on a rigorous evaluation of evidence
where possible
bull evidence is sparse but evolving
bull most preterm babies require stabilization rather than
resuscitation
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Acidndashbase physiology and blood gas interpretation in the neonateSusern tan
morag Campbell
Abstractacidndashbase balance describes the complex processes that work to main-
tain a stable extracellular pH for optimal cellular function the process
of balancing the production and neutralization of tissue acid provides a
great challenge for newborn infants who have significantly higher rates
of acid production than adults Factors which help maintain a stable
acidndashbase balance include buffers the respiratory system and renal sys-
tem Both intracellular and extracellular buffers resist changes in pH
the most important extracellular buffer system for maintaining stable
pH is the bicarbonate system in response to acidosis or alkalosis the
respiratory system balances the production of acid with the clearance
of Co2 by altering respiratory rate the kidneys provide a delayed but
sustained response to pH imbalance by excreting either acidic or alkaline
urine in response to systemic acidosis and alkalosis respectively in sick
premature infants these systems have a limited capacity completely to
control pH this review discusses the physiology of the three systems
which control acidndashbase balance patterns of clinical abnormalities in
acidndashbase status and their underlying causes are discussed We present
a systematic approach to blood gas analysis and interpretation in new-
born infants
Keywords acidosis alkalosis bicarbonate bloodndashgas analysis
metabolic pH
Introduction
Blood gas analysis is a routine procedure performed on newborn babies receiving respiratory support in the neonatal intensive care The combination of invasive and non-invasive assessment of ventilation and oxygenation enables clinicians appropriately to modify respiratory care according to each individual babyrsquos rapidly changing clinical status
Understanding the fundamentals of acidndashbase balance helps us to use blood gas analysis not only to assess respiratory sta-tus but also to provide information on metabolic status and the adequacy of tissue perfusion
Susern Tan MBBS MRCP is Clinical Fellow at the Neonatal Intensive Care
Unit 6th Floor North Wing St Thomasrsquo Hospital London SE1 7EH UK
Morag Campbell MBChB MRCP is Consultant Neonatologist at the
Neonatal Intensive Care Unit 6th Floor North Wing St Thomasrsquo
Hospital London SE1 7EH UK
paeDiatRiCS anD CHilD HealtH 184 17
What is understood by acid-base balance
Acidndashbase balance refers to the complex physiological processes used by the body to maintain a stable extracellular pH1 A serum pH within the range of 735ndash745 provides the ideal environment for cellular metabolism Maintaining a stable pH is critical as the metabolic activity of proteins is pH dependent and small changes in hydrogen ion (H+) concentration can potentially alter physio-logical function
Acids are substances that yield free H+ in solution while a base accepts H+ and in solution combines with an acid to neu-tralize it In the normal metabolic state H+ are continuously pro-duced and neutralized to maintain a steady pH balance12 The rate of H+ production is two to three times higher in neonates because of their rapid growth rates and increased acid production from protein turnover and bone mineralization The challenge of maintaining a stable pH through processing and neutralizing H+ is therefore greatest in newborn infants
Using exact values of H+ concentration to assess acidndashbase status is cumbersome and it is more commonly expressed as pH defined by the equation
pH = minuslog H+
Maintaining acidndashbase balance
The balance between production and excretion of acids in the body is controlled by buffer systems which have an immediate effect and by the respiratory and the renal systems
Buffer systemsBuffer solutions resist change in pH when acid or alkali is added due to their capacity to absorb or give up H+ The three main buffer systems in the body are the bicarbonate phosphate and protein systems1ndash3 The protein and phosphate buffer systems are intracellular and act as lsquosinksrsquo for extracellular H+ which are exchanged with intracellular potassium (K+) and sodium ions (Na+) In an acute metabolic acidosis hyperkalaemia may develop due to this H+ exchange4
The bicarbonate buffer system is extracellular and consists of a mixture of carbonic acid (H2CO3) and sodium bicarbon-ate (NaHCO3) This buffer system helps maintain a stable pH by soaking up excess H+ with HCO3
minus which in solution forms carbonic acid (H2CO3) Carbonic acid is a weak acid and readily dissociates to give CO2 which is transported in dissolved form to the lungs for excretion
H+ + HCO3minus harr H2CO3 harr H2O + CO2
The bicarbonate system therefore completes the neutraliza-tion of excess H+ and a stable plasma pH is maintained The relationships between pH HCO3
minus and CO2 in this system are described by the HendersonndashHasselbalch equation15
pH = 61 + log HCO3minus003 times CO2
where 61 is the log of the dissociation coefficient of carbonic acid and 003 the solubility of CO2 in plasma Buffers are most potent when there are equal amounts of H+ and HCO3
minus in solution The
2 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
bicarbonate system is not a potent buffer however as HCO3minus
and CO2 are readily altered by the body this system plays a very powerful role in pH homeostasis15
Respiratory regulationThe respiratory system adapts within minutes to hours as part of the acute response to acidosis This system modifies pH by balancing production of H+ with ventilatory clearance of CO2
H+ directly stimulates chemoreceptors in the respiratory cen-tre of the brainstem producing an increase in respiratory rate26 The response to respiratory acidosis is very rapid as CO2 easily diffuses across the bloodndashbrain barrier however in metabolic acidosis compensation is delayed until plasma bicarbonate fully equilibrates with cerebrospinal fluid (CSF) bicarbonate There is an inverse relationship between alveolar ventilation and partial pressure of dissolved carbon dioxide (PaCO2) a reduction in alveolar ventilation raises PaCO2 and decreases pH Changes in pH therefore affect alveolar ventilation and conversely changes in alveolar ventilation cause significant changes in pH
Renal regulationThe kidneys provide a delayed but sustained response to acidndashbase imbalances by excreting either acidic or alkaline urine In full-term and preterm babies the capacity for acid excretion and bicarbonate reabsorption is reduced as glomerular filtration rates are low and tubular function immature7 Renal function matures with gestation postnatal age and glucocorticoid and thyroid hormones78 Due to their limited capacity to preserve HCO3
minus newborn infants have lower serum bicarbonate levels and are predisposed to acidosis7
Bicarbonate is not effectively reabsorbed due to its size and electrical charge Instead intraluminal HCO3
minus combines with secreted H+ in tubular luminal fluid to produce carbonic acid which dissociates to give H2O and CO2 This CO2 diffuses into tubular cells combines with intracellular H2O and forms carbonic acid which liberates HCO3
minus and H+ HCO3minus is then
recovered to the circulation by exchange for chloride ions (Clminus) through the basal cell membrane247
Renal acid secretion occurs at all sites except the loop of Henle Primary active transport accounts for 5 and secondary for the remaining 95 of total H+ excretion Secondary trans-port involves an exchange between luminal Na+ and intracel-lular H+ Both ions bind to a membrane transport protein The Na+ concentration gradient between the tubular lumen and cells enables Na+ drag into the cell which generates energy to fuel active H+ excretion into the tubular lumen1ndash47
Quantifying acidosis
Standard base excess is a calculated value derived from PaCO2 and pH It is expressed as the mmollitre of base above or below normal buffer bases required to correct the pH to 74 at a PaCO2 of 40 mmHg A negative base excess or base deficit indicates an acidosis while a positive base excess indicates a relative alkalosis15
Anion gap is the measured difference between anions and cations in the blood
Anion gap = (Na+ + k+) minus (HCO3+Clminus)
paeDiatRiCS anD CHilD HealtH 184 17
Calculation of the anion gap enables clinicians better to define the underlying cause of a metabolic acidosis9 The common causes of an increased anion gap acidosis in neonates include lactic acidosis due to tissue hypoperfusion and hypoxia it may also be seen with certain inborn errors of metabolism and in uraemia910 The anion gap can help distinguish between the rela-tively benign non-anion gap hyperchloraemic acidosis seen in premature infants and a pathological lactic acidosis due to poor end-organ perfusion1011
Strong ion theory
Stewart described a complex acidndashbase model which proposed that H+ concentration results from the dissociation of water which is influenced by PaCO2 the strong ion difference and plasma weak acids12
Strong ions are ions that dissociate at normal body pH and include Na+ K+ and Clminus Weak acids in plasma which contrib-ute include albumin inorganic phosphate and plasma proteins their concentrations do not change with pH and are therefore a constant The effect of these factors and other unmeasured tissue ions on acidndashbase status can be quantified by the calculation of the strong ion gap (SIG)112 In the neonatal unit it is perhaps more important that we consider how principles of this model may relate to acidndashbase status rather than fully to quantify the SIG Theoretically low albumin and phosphate levels which fre-quently occur in premature infants by reducing the concentra-tion of weak acids can produce a relative alkalosis while high phosphate levels in renal failure may contribute to acidosis
Tissue oxygenation
Oxygenation is closely linked to acidndashbase status as optimal cel-lular function requires oxygen to fuel aerobic metabolism and produce energy In hypoxic conditions anaerobic metabolism predominates which is energy inefficient and results in a lactic acidosis1011
Tissue oxygen availability is related to regional blood flow haemoglobin level and haemoglobin oxygen affinity Arterial blood gases measure the partial pressure of dissolved oxygen (PaO2) which represents a small component of total oxygen con-tent the majority being transported bound to haemoglobin The relationship between percentage haemoglobin saturation (SaO2) and PaO2 is described by the sigmoidal oxyhaemoglobin disso-ciation curve which enables us to relate the two measures to each other235 The affinity of haemoglobin for oxygen is altered by local tissue factors Increases in temperature H+ PaCO2 and 23-diphosphoglycerate (DPG) levels shift the oxyhaemoglobin dissociation curve to the right reducing affinity for oxygen Decreases in temperature H+ PaCO2 and 23-DPG levels shift the curve to the left increasing oxygen affinity1ndash35 In the body haemoglobin oxygen affinity continuously changes increasing in the lungs to enable efficient oxygen uptake and decreasing at tissue level to provide efficient oxygen delivery to metabolically active tissues
Avoiding both hypoxia and hyperoxia is important in the neo-natal unit as deleterious effects of hypoxia are seen in infants with pulmonary hypertension1314 while hyperoxia is associated with an increased incidence of retinopathy of prematurity1516
3 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Clinical acidndashbase imbalances
Clinical acidndashbase imbalances can be respiratory metabolic or a mixture of both These abnormalities may be corrected by the acidndashbase regulatory mechanisms in the body in an attempt to maintain normal pH (Figure 1)
Respiratory acidosisThis occurs when any disorder leads to decreased alveolar ventilation Common causes of respiratory acidosis are listed in Table 1 Reduced respiratory clearance of CO2 means more dissolved CO2 accumulates in the plasma leading to increased production of carbonic acid and H+ Through chemoreceptor stimulation respiratory acidosis rapidly alters ventilation in an attempt to reduce CO226 Chemoreceptor mediated ventila-tory increases may only partly adjust in premature infants with underlying lung disease In babies with a sustained respiratory acidosis eg in chronic lung disease then metabolic compen-sation occurs through increased renal excretion of H+ and reabsorption of HCO3
minus slowly restoring pH to around 80 of normal47
paeDiatRiCS anD CHilD HealtH 184 17
The management of PaCO2 levels in infants receiving mechan-ical ventilation has important clinical implications Premature babies have impaired cerebral autoregulation17 and adverse neurological sequelae are reported in association with high PaCO2 levels18ndash20 Ventilation strategies which advocate lsquoper-missive hypercarbiarsquo have been developed to minimize airways damage from mechanical ventilation21 Published data suggest pulmonary benefits however the safe level of PaCO2 remains to be defined in premature infants2021
Respiratory alkalosisThis occurs when more CO2 is excreted than is produced by the body Pathological conditions leading to respiratory alkalosis are rare Hyperventilation in the neonatal setting is often iatrogenic or may be due to disorders in brainstem control of breathing including hypoxicndashischaemic encephalopathy or primary central nervous system abnormalities (see Table 1)
If respiratory alkalosis is sustained it may be compensated for by reduced reabsorption of filtered bicarbonate Reported adverse associations of low PaCO2 include periventricular leuco-malacia and intraventricular haemorrhage1922
K+
H+
Overventilation
CO2 + H2O harr H2CO3 harr H+ + HCO3ndash
Bicarbonate Buffer
Intracellular Buffer
uarr H+ excretionuarr HCO3
ndash absorption
uarr buffered H+
(NH4+ H2PO4
ndash)uarr ventilation rate
RespiratoryAcidosis
MetabolicAcidosis
darr CO2and uarr pH
RespiratoryAlkalosis
MetabolicAlkalosis
darr H+ anduarr pH
darr ventilation rate
uarrCO2
and darr pH
darr H+ excretiondarr HCO3
ndash absorption
uarrH+ and
darr pH
Brain
Brain
Intracellular Buffer
H+
K+
Sepsis
HypoxiaRDS
Metabolismand growth
Diuretics
Airwayobstruction
Neuromuscularproblems
IEM
Gastric losses
+ +
ndash -
Renal BufferRespiratory Buffer
Figure 1 mechanisms for regulation of extracellular pH iem inborn errors of metabolism RDS respiratory distress syndrome
4 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Common causes of acidndashbase imbalances
pH PCO2 H2CO3 Base excess Common neonatal causes
Respiratory acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
uarr normal normal bull upper airway obstruction choanal atresia
pierre-Robin sequence
bull lung abnormalities respiratory distress
syndrome transient tachypneoa of
newborn pneumonia meconium aspiration
syndrome pulmonary hypoplasia
congenital pulmonary malformations
bull Central hypoventilation hypoxic-ischaemic
encephalopathy intracranial haemorrhage
bull neuromuscular insufficiency congenital
myopathies congenital neuropathies
bull iatrogenic inadequate ventilatory settings
Compensated lower limit
of normal
uarr uarr gt+3
metabolic acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
normal darr ltminus3 increased anion gap
bull lactic acidosis sepsis hypoperfusion
shock necrotizing enterocolitis
bull inorganic acidosis inborn errors of
metabolism renal failure
normal anion gap
bull increased gastrointestinal H2Co3 losses
ileostomy diarrhoea
bull Renal tubular acidoses
Compensated lower limit
of normal
darr darr ltminus3
Respiratory alkalosis Uncompensated gt 745 darr normal normal bull iatrogenic excessive ventilatory settings
bull Compensatory hyperventilation hypoxic-
ischaemic encephalopathy
Compensated higher limit
of normal
darr darr ltminus3
metabolic alkalosis Uncompensated gt 745 normal uarr gt+3 bull gastric losses vomiting non-replacement
of excessive nasogastric aspirates
bull thiazide and loop diuretics
bull Hypokalaemia
Compensated higher limit
of normal
uarr uarr gt+3
Table 1
Metabolic acidosisThis frequently affects infants in the neonatal unit and has many causes1011 (see Table 1) There may be overproduction of tissue acid impaired acid clearance gastrointestinal loss of bicarbonate or an exogenous increased acid load eg chloride total paren-teral nutrition (TPN) or albumin1ndash323
Calculation of the anion gap to distinguish an increased anion gap acidosis from a non-anion gap acidosis is important both for treatment and prognosis1011 Acidosis stimulates respiratory compensation but this is limited in unstable infants Similarly renal compensation with improved HCO3
minus conservation is con-strained by tubular immaturity Treatment of the acidosis should be directed at the underlying cause eg hypoxia hypotension or excess Clminus rather than by administration of base
Metabolic alkalosisThis is unusual in neonates and is most frequently seen in infants with chronic lung disease or heart failure who are receiving diuretics Diuretics cause alkalosis by increasing renal fluid and Na+ losses An active process to reabsorb Na+ occurs in tubule cells which through enhanced H+ secretion and HCO3
minus reab-sorption produce alkalosis27
paeDiatRiCS anD CHilD HealtH 184 17
Metabolic alkalosis may also occur with excessive loss of gas-tric contents eg protracted vomiting or inadequate replacement of nasogastric aspirates (see Table 1)
Interpreting blood gases
Blood gas measurements can provide important diagnostic and prognostic information and a systematic approach to blood gas analysis is described in Table 2 The clinical management of infants with abnormal gases requires a good understanding of acidndashbase physiology and tissue oxygenation and an apprecia-tion of factors which may affect the reliability of samples
Arterial blood sampling is the gold standard however indwelling arterial catheters and arterial stab samples are usually restricted to infants who are critically ill or those who require sig-nificant ongoing intervention Gases are most frequently measured in capillary or venous samples which correlate well with arterial samples for PaCO2 pH and base excess in babies and children receiving intensive care These correlations however are not valid in infants with peripheral vasoconstriction and hypotension2324
Non-invasive monitoring techniques may enable us to reduce the frequency of blood gas sampling Transcutaneous monitoring
5 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
A systematic approach to blood gas analysis
1 Collect the relevant information
bull type of gas ndash capillary or arterial
bull Current respiratory support ndash document level
bull transcutaneous Co2 and Sao2 levels
bull Clarify no significant clinical events before sampling
2 pH accept a range between 730 and 745 in newborn
babies this is lower than in older children is there an
alkalosis (pH gt 745) or an acidosis (lt 730)
3 Co2 aim for a range between 45 and 65 kpa a paCo2 level
more than 65 kpa suggests inadequate alveolar ventilation
while less than 45 kpa suggests hyperventilation Correlate
values with non-invasive measures
4 o2 Can only be assessed from arterial gases aim for pao2
between 60 and 80 kpa Correlate results with pulse
oximetry levels
5 HCo3 and base excess normal HCo3 level is between 20 and
24 mmollitre and bases excess +3 to minus3
6 anion gap look at the anion gap and lactate to help identify
the cause of an acidosis normal lactate levels should be less
than 2 mmollitre
7 Respiratory or metabolic compensation look at the pH and
assess whether it is appropriate for the Co2 level or is there
evidence of compensation
8 interpret use both the clinical history and blood gas
findings to help you identify the primary problem aim your
management at treating the underlying cause
9 Reassess if clinical management changes have been made
repeat the blood gas after an appropriate time interval to
ensure improvement
Table 2
provides a highly accurate and reliable method for measuring PaCO2 through the skin it can however be technically difficult may cause tissue damage and is of limited reliability when peripheral perfusion is reduced25 Continuous end-tidal CO2 measurements correlate well with arterial CO2 values in patients with normal ventilation and perfusion however in babies with lung disease alveolar collapse small tidal volumes and rapid respiratory rates can make these measurements unreliable26 Despite its limitations transcutaneous monitoring provides the best method for CO2 trend monitoring in the neonatal intensive care unit (NICU)25
Oxygen saturation levels can be continuously measured non-invasively using pulse oximetry While oximetry is easy to perform and accurate on occasion SaO2 levels obtained may be unreliable when tissue perfusion is poor or with movement artefact SaO2 monitoring is highly sensitive at detecting hypoxia but is limited in detecting hyperoxia as at levels more than 90 small changes in SaO2 may result in unacceptably large increases in PaO227 It is therefore essential that SaO2 alarm limits are set for all neonates receiving respiratory support to detect hypoxia and prevent hyperoxia1627
Continuous non-invasive monitoring provides invaluable information when managing complex infants in the NICU but it does not replace the need for regular blood gas analysis
paeDiatRiCS anD CHilD HealtH 184 17
ReFeRenCeS
1 Kellum Ja Determinants of blood pH in health and disease
Crit Care 2000 4 6ndash14
2 Quigley R Baum m neonatal acid base balance and disturbances
Semin Perinatol 2004 28 97ndash102
3 Brouillette Rt Waxman DH evaluation of the newbornrsquos blood gas
status Clin Chem 1997 43 215ndash221
4 Chan JC acid-base disorders and the kidney Adv Pediatr 1983 30
401ndash471
5 Siggaard-andersen o the pH-log pCo2 blood acidndashbase nomogram
revised Scand J Lab Invest 1962 14 598ndash604
6 Saetta m mortola Jp interaction of hypoxic and hypercapnic stimuli
on breathing pattern in the newborn rat J Appl Physiol 1987 62
506ndash512
7 Baum m Quigley R postnatal renal development in Seldin DW
giebisch g eds the kidney physiology and pathophysiology new
york lippincott Williams and Wilkins 2000 p 703ndash726
8 ortiz la Quan a Weinberg a et al effect of prenatal
dexamethasone on rat renal development Kidney Int 2001 59
1663ndash1669
9 gabow pa Kaehny WD Fennessey pV goodman Si gross pa
Schrier RW Diagnostic importance of an increased serum anion gap
N Engl J Med 1980 303 854ndash858
10 lorenz Jm Kleinman li markarian K oliver m Fernandez J Serum
anion gap in the differential diagnosis of metabolic acidosis in
critically ill newborns J Pediatr 1999 135 751ndash755
11 Deshpande Sa platt mp association between blood lactate and
acid-base status and mortality in ventilated babies Arch Dis Child
1997 76 F15ndash20
12 Stewart pa modern quantitative acid-base chemistry Can J Physiol
Pharmacol 1983 61 1444ndash1461
13 Dakshinamurti S pathophysiologic mechanisms of persistent
pulmonary hypertension of the newborn Pediatr Pulmonol 2005
39 492ndash503
14 mourani pm ivy DD gao D abman SH pulmonary vascular
effects of inhaled nitric oxide and oxygen tension in
bronchopulmonary dysplasia Am J Respir Crit Care Med 2004
170 1006ndash1013
15 Deulofeut R Critz a adams-Chapman i Sola a avoiding hyperoxia
in infants le 1250 g is associated with improved short- and long-
term outcomes J Perinatol 2006 26 700ndash705
16 Chow lC Wright KW Sola a Can changes in clinical practice
decrease the incidence of severe retinopathy of prematurity in very
low birth weight infants Pediatrics 2003 111 339ndash345
17 Boylan gB young K panerai RB Rennie Jm evans DH Dynamic
cerebral autoregulation in sick newborn infants Pediatr Res 2000
48 12ndash17
18 Kaiser JR gauss CH pont mm Williams DK Hypercapnia during
the first 3 days of life is associated with severe intraventricular
hemorrhage in very low birth weight infants J Perinatol 2006 26
279ndash285
19 Fabres J Carlo Wa phillips V Howard g ambalavanan n Both
extremes of arterial carbon dioxide pressure and the magnitude of
fluctuations in arterial carbon dioxide pressure are associated with
severe intraventricular hemorrhage in preterm infants Pediatrics
2007 119 299ndash305
20 thome uH Carroll W Wu tJ et al outcome of extremely preterm
infants randomized at birth to different paCo2 targets during the
first seven days of life Biol Neonate 2006 90 218ndash225
6 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
21 Carlo Wa Stark aR Wright ll et al minimal ventilation to prevent
bronchopulmonary dysplasia in extremely-low-birth-weight infants
J Pediatr 2002 141 370ndash374
22 okumura a Hayakawa F Kato t et al Hypocarbia in preterm
infants with periventricular leukomalacia the relation between
hypocarbia and mechanical ventilation Pediatrics 2001 107
469ndash475
23 peters o Ryan S matthew l Cheng K lunn J Randomised
controlled trial of acetate in preterm neonates receiving parenteral
nutrition Arch Dis Child 1997 77 F12ndash15
24 yildizda D yapiciolu H yilmaz Hl Sertdemir y Correlation of
simultaneously obtained capillary venous and arterial blood gases
of patients in a paediatric intensive care unit Arch Dis Child 2004
89 176ndash180
25 aliwalas ll noble l nesbitt K et al agreement of carbon
dioxide levels measured by arterial transcutaneous and end tidal
methods in preterm infants 28 weeks gestation J Perinatol 2005
25 26ndash29
26 Hagerty JJ Kleinman me Zurakowski D et al accuracy of a new
low-flow sidestream capnography technology in newborns a pilot
study J Perinatol 2002 22 219ndash225
paeDiatRiCS anD CHilD HealtH 184 17
27 poets CF Wilken m Seidenberg J Southall Dp von der Hardt H
Reliability of a pulse oximeter in the detection of hyperoxemia
J Pediatr 1993 122 87ndash90
Practice points
bull a stable extracellular pH is important for optimal cellular
functioning
bull abnormalities in acidndashbase balance are regulated by buffer
systems and the respiratory and renal tract
bull maintaining a stable pH is challenging for newborn babies
due to their high rates of acid production and immature
regulatory mechanisms
bull arterial or capillary blood gases provide an effective way to
monitor acidndashbase balance in newborns
bull Blood gases should be analysed in a structured manner
assessing pH and then respiratory and metabolic components
bull the treatment of acidndashbase abnormalities should be directed
at the underlying problem not merely at correcting pH
7 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Recognition and management of neonatal seizuresmalcolm levene
AbstractSeizures are the most common major manifestation of central nervous
system dysfunction in the newborn there are many causes but perina-
tal asphyxia and haemorrhagicinfarction lesions account for about 75
there is now considerable evidence that frequent but short seizures in
the neonate affect subsequent neurodevelopmental outcome Studies
using eeg or modified continuous tracing of eeg activity (aeeg or CFm)
have shown that there is often electroconvulsive dissociation this re-
fers to poor correlation between electrical seizures and clinical seizures
Commonly used anticonvulsants appear to increase electroconvulsive
dissociation effective management of neonatal seizures has proved very
disappointing and less than 50 of seizures are abolished by first-line
anticonvulsant medication (phenobarbitone or phenytoin) Drugs such
as midazolam and lidocaine may further reduce seizures but require
more evaluation the challenge is to assess new and more effective anti-
convulsants which are themselves associated with little neurotoxicity
Keywords antiepileptic drugs eeg neonatal seizures neurodegeneration
Convulsions are the most common major neurological sign seen in newborn infants and their incidence estimated from large population studies is 26 per 1000 live births1 Premature infants are over four times more likely to have convulsions than full-term infants12 Neonatal status epilepticus (continuous seizure activity lasting 30 min or more) diagnosed clinically is rare and accounts for only 5 of infants with seizures1 although this is now recognized more frequently as the result of continuous EEG monitoring3
Neonatal convulsions are described as presenting in a num-ber of different ways and various seizure types can be seen in the same baby over a number of hours The frequencies of the various patterns of seizure activity are given in Table 1 In very premature babies and to a lesser extent in term infants minor movement abnormalities may be difficult to identify as subtle seizures These include lip smacking tongue thrusting mouth-ing pedalling type movements of the lower limbs or swimming movements of the arms Apnoea can be a common manifesta-tion of subtle seizures The signs can be protean and vary from baby to baby or even in the same baby Virtually any stereotypic
Malcolm Levene MD FMedSc FRCPCH FRCH is Professor and Head of
Department of Paediatrics and Child Health at University of Leeds Leeds
and Honorary Neonatologist at Leeds General Infirmary Leeds UK
paeDiatRiCS anD CHilD HealtH 184 178
movement may be a manifestation of a seizure disorder in the newborn
Aetiology
The more carefully the fitting baby is investigated the more likely it is that a cause for the seizures will be found A number of recent papers have described the aetiology of neonatal con-vulsions after extensive investigations14 Tekgul et al4 recently studied a consecutive group of full-term infants with evidence of neonatal convulsions (recognized both clinically and on EEG) and reported their outcome Table 2 summarizes these data as well as risk of moderate or severe disability for each causative factor Perinatal asphyxia is the commonest cause for convul-sions in term infants with haemorrhagic or ischaemic lesions also being common
Overall the prognosis for the group of term babies with con-vulsions was good 72 had a favourable outcome Where asphyxia (hypoxicndashischaemic insult) is the cause of neonatal convulsions the outcome is poor in 50 The prognosis for neonatal convulsions when they were due to arterial or cere-brovenous infarction or intracranial haemorrhage was generally good Individually inborn errors are a very rare cause of neo-natal convulsions but in view of the treatable nature of some of these it is essential that these be considered and investigated appropriately5
Patterns of seizure activity in the newborn
Movement pattern Frequency ()
Clonic 50
tonic 20
Subtle 10ndash35 depending on maturity
myoclonic 5
Table 1
Cause incidence and outcome of neonatal convulsions in term infants14
Aetiological factor Incidence () Poor outcome ()
asphyxia 38ndash40 50
Cerebral arteriovenous
infarction
20 0
intracranial haemorrhage 12ndash20 13
Congenital cerebral anomaly 5ndash10 100
Hypoglycaemiahypocalcaemia 3ndash19
infection 3ndash20
inborn error of metabolism 1
unknown cause 10ndash13 0
Refers to moderate and severe neurodevelopmental abnormalitynumbers too small to make meaningful predictions
Table 2
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Controversies in the clinical management of neonatal seizures
In recent years we have learnt much more about the neurobi-ology of seizures and their effect on the developing brain The neonatal brain is in a neurophysiologically hyperexcitable state compared to the more mature brain and therefore is more prone to seizure activity This is due largely to a relative excess of GABA neuroreceptors GABA receptors are usually inhibitory but in the immature brain they have a paradoxically excitatory effect This changes at about term in primates and with progressive develop-ment they adopt a neuroinhibitory role6
The propensity to seizures in the neonatal brain makes resolv-ing the balance of risks between continuing seizure activity on the one hand against potentially adverse effects of therapy on the other a very important equation Added to this is the problem of accurately diagnosing neonatal seizures and whether commonly used anticonvulsants are successful in controlling them
These conundrums can be posed as a series of challenging questions which are discussed below
Do neonatal convulsions cause brain injuryConvulsions are a sign of neurological compromise and may indi-cate significant underlying structural brain damage or biochemi-cal disturbance which may cause further brain damage in its own right There has been considerable debate about the scale of the disability that convulsions cause the immature brain over and above that due to the underlying cause Most of our knowledge comes from studies in rodents and these have provided some tentative answers to this question
Seizures in the mature brain lead to neuronal necrosis but studies in very young rat pups whose brain development is somewhat similar to full-term infants have shown that a series of five brief seizures on five successive days does not cause struc-tural neuronal damage but does produce morphological changes in hippocampal neurones and worryingly deficits in the rat learning and visual spatial memory function in adolescent and adult life7 A single prolonged neonatal convulsion in similarly immature rats does not produce any functional effects8 Others have shown that following priming of the neonatal rat brain by short seizures as described above a further insult comprising induction of status epilepticus in the same rats at an older age causes neuronal necrosis9 This has been referred to as the lsquotwo hit hypothesisrsquo10
A more specific question is does seizure activity in an already significantly compromised brain cause additional neuropathol-ogy Wirrell et al11 studied a series of immature rat pups with the induction of an hypoxicndashischaemic (asphyxial) insult fol-lowed by either chemically-induced fits or a control sham pro-cedure In the more severely asphyxiated animals the degree of brain damage was increased significantly in those that had the additional burden of induced seizures
In summary these studies show that the immature brain is more resistant to short frequent post-seizure damage than the mature brain but despite resulting in no loss of neuronal numbers the function of the brain is permanently affected in later life In the asphyxiated brain seizures appear to have an additional adverse effect on brain damage Furthermore the immature brain that has been lsquoprimedrsquo by early seizures is more
paeDiatRiCS anD CHilD HealtH 184 179
vulnerable to status epilepticus later in life It would appear from these data that frequent seizures in the human infant should be stopped and this begs the question as to whether currently used anticonvulsants effectively control neonatal seizures
Can we rely on clinical versus EEG diagnosis of neonatal convulsionsTraditionally the diagnosis of neonatal convulsions has been made by observation and description of the frequency of abnor-mal movements EEG has been technically difficult in the hostile electrical activity of a neonatal intensive care environment and considerable expertise is required for analysis of the trace It is usually not practical to undertake traditional EEG recordings at the time the baby shows abnormal movements More recently various technological developments have allowed more direct investigation of neuronal electrical activity by either video-EEG or compressed recording of the amplitude integrated EEG (aEEG or CFM)
Rennie et al3 at Kingrsquos College Hospital London have under-taken extensive evaluation of video-EEG and have found that this technique detects many convulsions not recognized by a single channel aEEG or CFM trace Of 19 infants with evidence of convulsions on EEG only four were recognized on CFM but this may have been due to the observersrsquo lack of experi-ence with this technique In other centres that have developed appropriate expertise aEEG or CFM has proved more sensitive to the detection of seizures Video-EEG studies have also shown that many movements interpreted by experienced clinicians to be seizures are not associated with abnormal cortical activity Conversely many electrical seizures are not associated with abnormal movements This is referred to as electroconvulsive dissociation
In summary clinical observation alone to detect the fitting baby is unreliable in that it may either over-detect seizure activ-ity which is not present on EEG or under-detect clinical seizures in infants with EEG-proven convulsions The decision as to which babies to treat with antiepileptic drugs therefore becomes somewhat arbitrary
Do anticonvulsants stop neonatal seizuresAlthough neonatal seizures are common there are few random-ized controlled trials assessing the benefits of antiepileptic drugs (AEDs) in the treatment of this condition Phenobarbitone is the most widely used first-line AED and in an Australasian study 95 of neonatologists and paediatric neurologists used this drug as first-line management12 The most commonly used loading dosage is 20 mgkg but regimens of up to 40 mgkg have been recommended (Table 3)13 Four trials have evaluated the effect of phenobarbitone in abolishing neonatal seizures Two of these studies used EEG to monitor response to the drug1415 and one compared phenobarbitone with phenytoin15 In the latter study seizures were completely controlled in only 43 of babies and in the group where phenytoin was the first drug used com-plete seizure control was achieved in 45 This study switched babies from their first AED to the other if complete control was not obtained on EEG monitoring after exposure to first-line therapy In babies who had been given phenobarbitone as first-line therapy seizure control was only achieved in 57 after phenytoin was added In those given phenytoin first complete
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Dosage regimens for first- second- and third-line anticonvulsants in the neonatal period
Loading dose Second loading dose if first
unsuccessfulMaintenance dose
phenobarbitone 20 mgkg by slow iv injection 10 mgkg iv 25ndash5 mgkg od
phenytoin 20 mgkg iv over 20 min not recommended
midazolam 150ndash200 μgkg iv infusion 1 μgkgmin iv infusion increasing to 5 μgkgmin
until favourable response
lidocaine 2 mgkg iv over 10 min 6 mgkgh for 6 h iv then 4 mgkgh for 12 h then
2 mgkgh for 12 h
lorazepam 005ndash01 mgkg by slow iv injection
Diazepam 03ndash04 mgkg iv over 3ndash5 min
lidocaine should not be used if the infant has previously been treated with phenytoin
Table 3
seizure control was achieved with the adding of phenobarbitone in 62
Boylan et al14 assessed the efficacy of phenobarbitone (20ndash40 mgkg iv over 20 min) in 14 babies monitored by video-EEG in only four was there complete abolition of seizures and in the other 10 electroconvulsive seizure activity increased whereas clinical evidence of seizures reduced This has been termed elec-troclinical dissociation and anticonvulsant drug use in the new-born appears to increase this feature They also showed that the babies least likely to respond to the first-line AED are those with the most abnormal background EEG
Two studies have evaluated the use of phenobarbitone in babies who had sustained significant asphyxial insult at birth Hall et al13 compared high-dose phenobarbitone (mean 39 mgkg) versus standard dose (27 mgkg) and reported fewer convul-sions and a significant reduction of severe disability or death in the high dose group (RR 030 CI 010ndash093) A recent study from India16 of babies with hypoxicndashischaemic encephalopathy ran-domized 25 babies to phenobarbitone (20 mgkg loading dose) and compared them with 20 control babies Only 2 of 25 (4) in the phenobarbitone group developed convulsions compared with 8 of 20 (40) in the control group (p = 001) Because of the specific enrolment criteria (asphyxial insult) neither of these studies is strictly comparable to the studies by Painter et al15 and Boylan et al14 whose intention was to assess the efficacy of first-line anticonvulsant therapy on convulsions of any cause diagnosed either clinically or by EEG
Other anticonvulsants used as second- and third-line drugs have been subject to few studies in the newborn Midazolam is administered as a bolus followed by continuous infusion A recent study17 has shown that in 10 of 13 neonates given intravenous midazolam for status epilepticus control of electri-cal seizures was achieved within the first hour of treatment having been previously shown to be refractory to phenobarbi-tone treatment Some of these babies required a second bolus infusion of midazolam to obtain control of all electrographic seizures
In some parts of Europe lidocaine is used as a third-line anti-convulsant Malingre et al18 evaluated 20 infants refractory to
paeDiatRiCS anD CHilD HealtH 184 180
both phenobarbitone and midazolam and who were then given lidocaine by continuous infusion Lidocaine was effective in abolishing electroconvulsive seizures diagnosed by aEEG in 76 of the treatment courses studied No babies developed cardiac arrhythmias a previously reported complication of lidocaine in older patients As a result of pharmacokinetic studies the dosage regimen has been modified (see Table 3)
In summary phenobarbitone is effective in seizure control in less than 50 of babies and even when combined with phe-nytoin the efficacy of these drugs together remains poor More worrying is the observation that phenobarbitone tends to reduce clinically evident seizures thereby giving the clinician a false sense of security whilst having little or no effect on the num-bers of electroconvulsive disorders This has been summarized appropriately as lsquoafter all these years we still love what doesnrsquot workrsquo19 Both midazolam and lidocaine infusions appear to be effective in abolishing severe seizures in some infants resistant to phenobarbitone Lidocaine should not be given to babies previ-ously exposed to phenytoin for fear of a synergistic adverse effect on cardiac rhythm
Do antiepileptic drugs cause brain damageA riskndashbenefit analysis is needed to evaluate the efficacy of anticonvulsants in stopping neonatal seizures which is poor with standard anticonvulsants as discussed above against the risk of administering the anticonvulsant drugs themselves Phenobarbitone has been reported to have adverse effects on the developing brain including inhibition of brain growth20 neuronal toxicity21 and adverse behavioural and cognitive effects into adult life when administered to young animals22 Phenytoin shows unpredictable plasma levels and potential cardiotoxicity
Recent studies have shown an effect of AED exposure on the developing brain by causing neurodegeneration23 Phenytoin administration to immature rat pups at doses which produce serum levels similar to those achieved in human neonates was associated with widespread neuronal death as a result of apop-tosis (programmed cell death) Phenobarbitone had a similar effect when a dosage regimen similar to 40 mgkg was used and
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
this effect was maximal in the more immature brain Diazepam and clonazepam also resulted in a similar effect Midazolam and lidocaine were not tested in this study The combination of phenobarbitone or phenytoin with diazepam had a particularly profound effect on neurodegeneration
In summary recent data suggest that the commonly used AEDs for neonatal convulsions may in themselves cause neuro-degeneration due to apoptosis with lasting effects on develop-ment Many babies with neonatal convulsions are treated with at least two AEDs and this may produce more severe adverse effects than the seizures themselves
Practical management of neonatal seizures
Assimilation of these data and formulation of a rational policy is difficult when faced with a fitting neonate on an intensive care unit and pressure on the medical staff to lsquodo somethingrsquo but it is important to accept that sometimes doing nothing is preferable to using potentially dangerous drugs in a situation which does not warrant such intervention Many babies who have normal interseizure neurological clinical findings and whose seizures are relatively brief and infrequent probably do not need anticon-vulsant medication A normal or near-normal background EEG trace should reassure the clinician that anticonvulsants can be withheld
Some causes of neonatal convulsions are treatable such as meningitis hypoglycaemia hypocalcaemia and inborn errors of metabolism and each baby should be rapidly and carefully investigated for cause of the convulsions
In some babies clinical assessment of seizures is difficult ie when the baby is very sick small or paralyzed Sometimes it may be difficult to assess the significance of certain movement pat-terns Under these circumstances an EEG may prove to be very helpful In many units EEG is not available out of hours and a simple aEEG or CFM is strongly advised Modern instruments are very simple to apply and prolonged or frequent seizures should be identified with only moderate training The printout can be faxed to a more senior doctor if there is doubt as to what is shown on the trace
The balance of knowledge now is that frequent seizures cause additional damage to the developing brain and that treatment to abolish the seizures is warranted Unfortunately there is little evidence that the majority of seizures can be effectively termi-nated by current standard therapy Furthermore it appears that the more abnormal the background EEG the more difficult it is to control the seizures Nevertheless a written protocol for the management of neonatal convulsions is required on each unit Phenobarbitone and phenytoin remain the mainstay of treat-ment although their effectiveness is disappointing There is little to suggest that midazolam is more effective than lidocaine as third-line therapy but lidocaine is precluded if phenytoin has been previously used
In view of the anxiety as to the neurodegenerative effects on the immature brain of most anticonvulsants used in the neonatal period (particularly when multiple drugs are used) it is prefer-able to use only one drug to maximum dosage before introduc-ing a second In addition the duration of anticonvulsants should be minimized and the drugs stopped at the earliest opportu-nity It is my practice to stop anticonvulsants prior to discharge
paeDiatRiCS anD CHilD HealtH 184 18
from hospital if the baby is neurologically normal on clinical examination
REFEREnCES
1 Ronen gm penney S andrews W the epidemiology of clinical
neonatal seizures in newfoundland a population-based study
J Pediatr 1999 134 71ndash75
2 lanska mJ lanska DJ Baumann RJ et al a population-based study
of neonatal seizures in Fayette County Kentucky Neurology 1995
45 724ndash732
3 Rennie Jm Chorley g Boylan gB et al non-expert use of the
cerebral function monitor for neonatal seizure detection Arch Dis
Child Fetal Neonatal Ed 2004 89 F37ndashF40
4 tekgul H gauvreau K Soul J et al the current etoliologic profile
and neurodevelopmental outcome of seizures in term newborn
infants Pediatrics 2006 117 1270ndash1280
5 Surtees R Wolf n treatable neonatal epilepsy Arch Dis Child 2007
92 659ndash661
6 Ben-ari y Holmes gl effects of seizures on developmental
processes in the immature brain Lancet Neurol 2006 5 1055ndash
1063
7 Holmes gl gairsa Jl Chevassus-au-louis n et al Consequences of
neonatal seizures in the rat morphological and behavioral effects
Ann Neurol 1998 44 845ndash857
8 Stafstrom Ce Chronopoulos a thurber S et al age-dependent
cognitive and behavioural deficits following kainic-acid inducing
seizures Epilepsia 1993 34 420ndash432
9 Schmid R tandon p Stafstrom Ce et al effects of neonatal seizures
on subsequent seizure-induced brain injury Neurology 1999 53
1754ndash1761
10 Hoffmann aF Zhao Q Holmes gl Cognitive impairment following
status epilepticus and recurrent seizures during early development
support for the ldquotwo-hit hypothesisrdquo Epilepsy Behav 2004 5
873ndash877
11 Wirrell eC armstrong ea osman lD et al prolonged seizures
exacerbate perinatal hypoxic-ischemic brain damage Pediatr Res
2001 50 445ndash454
12 Carmo KB Barr p Drug treatment of neonatal seizures by
neonatologists and paediatric neurologists J Paediatr Child Health
2005 41 313ndash316
13 Hall Rt Hall FK Daily DK High-dose phenobarbital therapy in term
newborn infants with severe perinatal asphyxia a randomized
prospective study with three-year follow-up J Pediatr 1998 132
345ndash348
14 Boylan gB Rennie Jm pressler Rm et al phenobarbitone neonatal
seizures and video-eeg Arch Dis Child Fetal Neonatal Ed 2002 86
F165ndash170
15 painter mJ Scher mS Stein aD et al phenobarbital compared with
phenytoin for the treatment of neonatal seizures N Engl J Med
1999 341 485ndash489
16 Singh D Kumar p narang a a randomized controlled trial of
phenobarbital in neonates with hypoxic ischemic encephalopathy
J Matern Fetal Neonatal Med 2005 18 391ndash395
17 Castro Conde JR Borges H Domenech martinez e et al midazolam
in neonatal seizures with no response to phenobarbital Neurology
2005 64 876ndash879
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
18 malingre mm Van Rooij lgm Rademaker Cma et al Development
of an optimal lidocaine infusion strategy for neonatal seizures Eur
J Pediatr 2006 165 598ndash604
19 Sankar R painter mJ neonatal seizures after all these years we still
love what doesnrsquot work Neurology 2005 64 776ndash777
20 Diaz J Schain J Bailey Bg phenobarbital-induced brain growth
retardation in artificially reared rat pups Biol Neonate 1977 32 77ndash82
21 mattson RH phenobarbital toxicity in levy RH Dreifuss Fe
mattson RH et al eds antiepipeptic Drugs 3rd edn new york
Raven 1985 p 341ndash355
22 mikati ma Holmes gl Chronopoulos a et al phenobarbital
modifies seizure-related brain injury in the developing brain Ann
Neurol 1994 36 425ndash453
23 Bittigau p Sifringer m genz K et al antiepileptic drugs and
apoptotic neurodegeneration in the developing brain Proc Natl
Acad Sci U S A 2002 99 15089ndash15094
paeDiatRiCS anD CHilD HealtH 184 182
Practice points
bull the clinician needs to be aware that almost any repetitive
stereotype movement pattern can be a manifestation of
neonatal seizures
bull eeg is important in defining neonatal seizures
bull Frequent short-lived seizures have been shown to cause long-
term neurodevelopmental problems
bull Conventional anticonvulsant medication is ineffective in
abolishing neonatal seizures in greater than 50 of cases
bull there is evidence that exposure of the neonatal brain to
multiple anticonvulsants causes neuronal death
bull Future research is needed to evaluate more effective
anticonvulsants for treating this condition
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
Emotional support for families of sick neonatesMarina nicolaou
cristine Glazebrook
AbstractParents of sick neonates experience high levels of stress anxiety and
depression Most interventions with families of sick infants have focused
on fostering the motherndashinfant relationship through the provision of
information about infant developmental needs or through increased
motherndashinfant contact Many of these studies have reported improved
maternal well-being though there are some concerns about the scope
and practicality of large-scale interventions The few studies to have
prioritized emotional support for parents of sick neonates have pro-
duced encouraging results even interventions requiring relatively few re-
sources such as telephone support parent-to-parent support and group
support have been associated with reduced psychological morbidity for
parents The needs of parents can change throughout their infantrsquos hos-
pitalization and not all want or benefit from the provision of additional
support Thus neonatal intensive care units should aim to provide a
varied flexible and sustainable programme of support options Further
research should focus on the needs of fathers
Keywords mental health neonatal intensive care parents
The admission of an infant to neonatal care is acknowledged to be a source of considerable distress for families This review aims to explore evidence for the psychological impact on families of having an infant in neonatal intensive care and to identify evi-dence for the effectiveness of interventions to promote parental well-being It will conclude with recommendations for strategies to support parents of vulnerable infants and suggestions for fur-ther research
Psychological impact of neonatal care for parents
The majority of research examining the effect on parents of having a sick neonate has focused on families of premature or low birthweight infants Such research has found that parents with a sick neonate exhibit high levels of stress compared to normative samples and to parents of healthy full-term infants1 Singer et al2 examined the stress experienced by mothers of high-risk very low birthweight (VLBW) low-risk VLBW and term
Marina Nicolaou MPhil is a Teaching Assistant at the School of
Community Health Sciences University of Nottingham Nottingham UK
Cristine Glazebrook PhD is a Professor of Health Psychology at the School
of Community Health Sciences University of Nottingham Nottingham UK
PaeDiaTrics anD cHilD HealTH 184 196
infants Several self-report measures were used including the Brief Symptom Inventory the Parenting Stress Index (PSI) the Impact on Family Scale and the Family Inventory of Life Events and Changes (FILE) Mothers of VLBW infants had more psycho-logical distress at 1 month compared to mothers of term infants Mothers of high-risk VLBW infants also reported high psycho-logical distress at 2 years and high levels of parenting stress at 3 years Mothers have also been found to have higher stress levels compared to fathers Shaw et al3 examined the prevalence of acute stress disorder (ASD) in 40 parents whose infants were in the neonatal intensive care unit (NICU) Nearly half of the moth-ers (44) met the criteria for ASD although none of the fathers did Furthermore the severity of the symptoms (measured by the number of concurrent symptoms) was greater for the moth-ers than for the fathers3 The reasons behind this difference have been widely speculated with some believing that it is due to the mothersrsquo greater psychological involvement with the infant as evidenced by their general greater vulnerability to postpartum psychological disorder It could also reflect gender differences in coping style
Having an infant who requires intensive medical care repre-sents a significant emotional burden for families Not only is there extreme anxiety surrounding the infantrsquos health and distress for the childrsquos suffering there is also the unfamiliar and intimidating environment of the NICU to adjust to Hopper in her review of the literature identified sources of stress for parents of sick neo-nates as falling into three areas4 Situational factors included the severity of the infantrsquos illness and how parents adapted to the life crisis of having a sick infant Personal factors involved parental emotions about their roles and the instrumental and informa-tional support which were available to them The third area was classified as environmental sources of stress and included the environment of the NICU and the relationship between parents and members of staff This relationship has been examined by several studies in the nursing literature nurses are seen as ide-ally placed to provide the necessary support and information to parents with sick neonates However whilst some studies have shown that supportive and helpful hospital staff can have a posi-tive effect on parents other studies have highlighted the prob-lems and difficulties which can manifest It has been shown that parents and nurses often have very different ideas about issues eg the necessary skills and competencies needed in an NICU or the characteristics that make a lsquogood motherrsquo
Research has shown that there may be a relationship between high levels of parental stress and an increased likelihood of depression5 Postpartum depression is a psychiatric illness which appears in 10ndash15 of postpartum women Its reported preva-lence rates however have ranged from less than 10 up to 306 depending on the instruments used the population exam-ined and the timing of the research Several factors have been found to be associated with postpartum depression including poor social support and infant-related stressors6 Evidence indi-cates that postnatal depression may be underreported and this is of concern since the mental and psychological health of the mother can affect her relationship with her infant and thus the infantrsquos cognitive and emotional development5 Depressed moth-ers appear to look touch and talk to their infants less frequently and also appear to show fewer positive and more negative faces7 The vocalizations of mothers suffering with depression have also
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
been found to be less effective at promoting cognitive growth and learning in infants8
If researchers are interested in finding ways of providing sup-port for families of sick neonates then they must listen to what such families perceive their needs to be in order to avoid increas-ing anxiety and distress Furthermore the provision of appropri-ate support be it emotional informational or social will enhance parental coping abilities increase self-esteem and reduce anxiety It should be noted though that the research conducted around these issues has often taken lsquosupport needsrsquo as being synony-mous with lsquoinformation needsrsquo Such studies have examined the type the amount and quality of information that parents receive and perceive themselves as needing but have not explored in equal depth the perceived emotional support needs of families who have a sick infant In addition the needs of parents may change throughout their infantrsquos illness Ward examined the per-ceived needs of 52 parents of infants in an NICU9 Parents rated the needs of their hospitalized infant as most important along with the need to be reassured Interestingly they ranked their support needs as least important This research was conducted during the first week of the infantsrsquo hospitalization however which would explain the preoccupation of the parents with the infantrsquos health These results demonstrate that if researchers want to find ways of providing emotional support to parents of sick neonates they must be prepared not only to listen to parents but also to be flexible enough to satisfy the parentsrsquo changing needs and expectations
Interventions aimed at supporting parents
Most interventions that been evaluated in controlled studies have focused on supporting the motherndashinfant relationship and provid-ing information on infant development Many of these interven-tions have included the aim of improving the parental emotional state and thus psychological outcomes such as stress or anxi-ety have been assessed However few studies appear to include fathers This means that strategies implemented to provide emo-tional support to families of sick neonates are often derived from interventions tailored for mothers even though fathers may have different emotional needs
A wide range of interventions with mothers and infants has been evaluated in the NICU Increasing motherndashinfant contact through kangaroo care has been found to reduce maternal anxiety1011 and educational programmes delivered to fami-lies in the NICU have also been associated with reduced emo-tional difficulties in parents12ndash14 Kaaresen and colleagues implemented an intervention which consisted of eight sessions before discharge and four home visits all by trained nurses The sample included 71 premature infants in the intervention group 69 premature infants in the control group and 74 infants in the full-term control group The randomized controlled trial found that the intervention reduced parenting stress in both mothers and fathers of premature infants compared to controls to a level equivalent to parents in the term control group13 At 6 months corrected age mothers of preterm infants who had not received the intervention had total PSI scores which were 17 points higher than the mothers of infants born at term (an effect size of 057) A similar study evaluated the efficacy of an educationalndashbehavioural programmendashCreating Opportunities for
PaeDiaTrics anD cHilD HealTH 184 19
Parent Empowerment (COPE) ndash through a randomized controlled trial with 260 families of premature infants14 COPE was a four-phase educationalndashbehavioural programme which began as early as 2ndash4 d after mothers had given birth and continued until 1 week after discharge from the NICU The programme consisted of audiotaped and written infant behaviour information along with photographs which focused on common behaviours and characteristics of premature infants It also included various par-ent activities in the form of a four-phase workbook which aimed to assist mothers in the implementation of the experimental infor-mation COPE was found significantly to reduce maternal stress in the NICU as well as maternal anxiety and depressive symptoms after hospitalization In contrast a cluster randomized trial of a parenting intervention delivered to mothers of very premature infants from soon after birth showed no benefits for parenting stress1 The authors hypothesized that the intervention had not been of sufficient intensity particularly in the weeks surrounding discharge Neonatal care presents a significant barrier to parent-ing in the early weeks following a very preterm birth and so inter-ventions which focus on the developmental needs of infants and the parentndashchild relationship should particularly aim to support parents as they take on the parenting role There was also concern that the intervention had failed to reach those most at risk
Since large-scale projects can be costly to implement and may often fail to reach the families in most need it may be wiser to focus on intervention programmes which are more practical and easier to implement within a neonatal care setting Research has shown that even interventions which are based on one-off meet-ings with parents of sick neonates can be effective Jotzo and Poets examined the effect of an intervention programme aimed at reducing the severity of traumatic responses as a result of giv-ing birth prematurely15 Their programme consisted of a one-off intervention meeting along with additional psychological help throughout the hospitalization of the infant The meeting cov-ered a variety of issues including a reconstruction of the events shortly before and after the infantrsquos birth relaxation techniques discussion of coping strategies available resources and social support and support during emotional outbursts The measures used included the Impact of Event Scale (IES) and the Peritrau-matic Dissociative Experience Questionnaire At discharge the mothers who received the intervention were found to have a significantly lower traumatic impact as a result of premature birth Furthermore fewer mothers in the intervention group showed symptoms of clinically significant psychological trauma at discharge compared to mothers in the control group (36 vs 76)15 The lsquoParents Circle Programrsquo is another intervention with a similar structure16 This consisted of a 90 min session for parents with the aim of enhancing the developing relationship between parents and infants and to offer parents support A total of 104 parents (59 mothers and 45 fathers) and 44 members of hospital staff were asked to evaluate the programme and their results were analysed using content analysis Families reported gaining perspective on their situation feeling supported becom-ing aware of cues and optimizing interactions and becoming aware of available resources Parents and staff alike felt that participating in the intervention helped parents overcome the difficulties associated with the early time of their infantrsquos hos-pitalization Additional studies have also found positive results with fairly minimal interventions including discussion groups
7 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
in the NICU music during kangaroo care and pairing mothers of sick neonates with trained mothers who had been through similar experiences
Parent support programmes
Parent support programmes (PSPs) which are based in NICUs can provide parents with the opportunity to talk to parents who have been in similar situations and also to discuss their emo-tions with professionals who can help them cope with their situa-tion111718 The parent-to-parent support programme for mothers of preterm infants evaluated by Preyde and Ardal included edu-cational parental support group meetings and individual par-ent-to-parent support (primarily telephone support)19 Measures used included the Parental Stressor Scale NICU the State and the Trait Anxiety Inventories and the Beck Depression Inven-tory After 4 months of participation mothers in the intervention group reported lower levels of stress state anxiety and depres-sion compared to control group mothers The authors speculated however that the participants who were able to meet face to face with other parents were those who benefited the most Hurst conducted a comprehensive survey of an NICU-based PSP This PSP was provided in a variety of formats including a weekly parent support group hospital visitation and 24-h telephone sup-port20 Of the 477 participants 303 families used the PSP dur-ing a 2-year evaluation period with 78 using only one form of support and 18 using two forms Of a sub-sample of 48 parents asked to complete an evaluation of the PSP 92 stated that they would recommend such a programme to other parents Furthermore the majority of parents felt that it made them feel supported and helped them deal with their emotions20 This is an indication that such programmes can be very successful in sup-porting parents throughout their infantrsquos hospitalization It also shows that it can be beneficial to give parents several options and formats when it comes to such support services It is impor-tant to consider though that both the Hurst and the Preyde and Ardal studies found that some participants did not find the sup-port programmes helpful even reporting that they had caused them increased stress and anxiety Therefore it should not be assumed that support programmes will suit every individual and will provide the required support for all parents1920 NICUs need to be flexible enough to provide parents with a range of forms of support to choose from
The increased understanding of the strains that parents of sick neonates have to deal with has also led to efforts to improve customary practices in NICUs Family-centred care focuses on infants and their needs and attempts to redefine the relationship between parents and caregivers These practices strive to provide parents with support during their infantrsquos illness by focusing on freely sharing information and on the collaboration between parents and hospital staff Family-centred care has been found to be associated with several beneficial outcomes including improved parental satisfaction increased parental comfort staff satisfaction and decreased parental stress18 Research is already examining these practices and questioning how these can be improved further Such research reflects the increasing effort focused on lsquohumanizingrsquo the environment in NICUs in order to make parents feel more comfortable about spending time with their infants
PaeDiaTrics anD cHilD HealTH 184 19
Conclusion
Surprisingly few interventions have prioritized the provision of emotional support for parents of sick neonates or accounted for the changing needs and wishes of parents over the course of their infantrsquos care Large-scale supportive education-based inter-ventions have been shown to be effective in reducing parental distress However the feasibility and sustainability of such pro-grammes should also be considered Programmes which require significant additional resources can be expensive and there are also issues of training and quality control Interventions which require significant input from parents may also place additional burdens on families making them potentially less accessible to those most at risk Arguably the aim should be to explore ways of providing acceptable and effective informational support which could be complemented by emotional support from health professionals and from other parents in the unit Increasingly studies are exploring the use of computers and multimedia as an engaging flexible and cost-effective method of targeting indi-vidual needs and providing support and information Such com-puter-based and interactive multimedia interventions have been found to be successful with a range of patient groups and could therefore be examined as a complementary method of providing informational support to families with sick neonates
REfEREnCEs
1 Glazebrook c Marlow n israel c et al randomised trial of a
parenting intervention during neonatal intensive care Arch Dis Child
Fetal Neonatal Ed 2007 92 F438ndash443
2 singer lT salvator a Guo s collin M lilien l Baley J Maternal
psychological distress and parenting stress after the birth of a very
low-birth-weight infant JAMA 1999 281 799ndash805
3 shaw rJ Deblois T ikuta l Ginzburg K Fleisher B Koopman c
acute stress disorder among parents of infants in the neonatal
intensive care nursery Psychosomatics 2006 47 206ndash212
4 Hopper a sources of stress for parents of a sick neonate a
literature review Pediatr Nurs 2000 30 29ndash32
5 Davis l edwards H Mohay H wollin J The impact of very
premature birth on the psychological health of mothers Early Hum
Dev 2003 73 61ndash70
6 Bernazzani O saucier J-F David H Borgeat F Psychosocial
predictors of depressive symptomatology level in postpartum
women J Affect Disord 1997 46 39ndash49
7 Field T infants of depressed mothers Infant Behav Dev 1995 18
1ndash13
8 Kaplan Ps Bachorowski J-a Zarlengo-strouse P child-directed
speech produced by mothers with symptoms of depression fails
to promote associative learning in 4-month-old infants Child Dev
1999 70 560ndash570
9 ward K Perceived needs of parents of critically ill infants in
a neonatal intensive care unit (nicU) Pediatr Nurs 2001 27
281ndash286
10 lai Hl chen cJ Peng Tc et al randomized controlled trial of music
during kangaroo care on maternal state anxiety and preterm infantsrsquo
responses Int J Nurs Stud 2006 43 139ndash146
8 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
11 Tallandini Ma scalembra c Kangaroo mother care and mother-
premature infant dyadic interaction Infant Ment Health J 2006 27
251ndash275
12 Ohgi s Fukuda M akiyama T Gima H effect of an early intervention
programme on low birthweight infants with cerebral injuries
J Paediatr Child Health 2004 40 689ndash695
13 Kaaresen Pi ronning Ja Ulvund se Dahl lB a randomized
controlled trial of the effectiveness of an early-intervention program
in reducing parenting stress after preterm birth Pediatrics 2006
118 e9ndash19
14 Melnyk BM Feinstein nF alpert-Gillis l et al reducing premature
infantsrsquo length of stay and improving parentsrsquo mental health
outcomes with the creating opportunities for parent empowerment
(cOPe) neonatal intensive care unit program a randomized
controlled trial Pediatrics 2006 118 e1414ndash1427
15 Jotzo M Poets cF Helping parents cope with the trauma of
premature birth an evaluation of a trauma-preventive psychological
intervention Pediatrics 2005 115 915ndash919
16 Pearson J andersen K evaluation of a program to promote positive
parenting in the neonatal intensive care unit Neonatal Netw 2001
20 43ndash48
17 roman l lindsay J Boger r et al Parent-to-parent support
initiated in the neonatal intensive care unit Res Nurs Health 1995
18 385ndash394
18 Meyer ec coll cTG lester BM Boukydis cFZ McDonough sM Oh w
Family-based intervention improves maternal psychological well-
being and feeding interaction of preterm infants Pediatrics 1994
93 241ndash246
PaeDiaTrics anD cHilD HealTH 184 19
19 Preyde M ardal F effectiveness of a parent ldquobuddyrdquo program for
mothers of very preterm infants in a neonatal intensive care unit
CMAJ 2003 168 969ndash973
20 Hurst i One size does not fit all Parentsrsquo evaluations of a support
program in a newborn intensive care nursery J Perinat Neonatal
Nurs 2006 20 252ndash261
Practice points
bull Parents of sick neonates experience significant distress and
exhibit higher levels of stress anxiety and depression than
parents of healthy infants
bull educational support emotional support and increased
motherndashinfant contact have been shown to promote maternal
well-being
bull emotional support for fathers has been largely neglected in
the research literature
bull Parents benefit from a choice of supportive facilities which
could include face-to-face sessions with health professionals
telephone support hospital visitation parent-to-parent
support and unit-based group support meetings
bull Parentsrsquo support needs can change during their infantrsquos
hospitalization and not all parents want or benefit from the
provision of additional information and emotional support in
the neonatal unit
9 copy 2008 elsevier ltd all rights reserved
Personal Practice
When should enteral feeds be started in preterm infantsnicholas D embleton
AbstractPaediatricians are regularly faced with the question of when best to start
enteral feeds in preterm infants this is important as longer term out-
come may be compromised by sub-optimal nutrition in early life clinical
factors that may affect the decision to start and the risk and benefits
are discussed
Keywords breast milk feeding nutrition parenteral nutrition
Key points in the history
Alice is lsquonutritionally vulnerablersquo and whilst this may not be immediately apparent it will affect her long term outcome Her energy stores are extremely limited and consist primarily of pro-tein She has less than 5 fat and little energy associated with stored glycogen She is losing about 1 gkgd protein equivalent so she needs at least that and a minimum of 50ndash60 kcalkg of energy just to maintain the status quo let alone grow
Her weight is on the 25th centile Review of any antenatal his-tory may reveal whether fetal growth was normal Fetal growth retardation can occur with a weight greater than 10th centile The presence of antenatal absent or reversed end diastolic flow in the umbilical artery indicates poor gut blood flow This increases the risk of necrotizing enterocolitis (NEC) and might suggest a more cautious approach to starting feeds1
She has no important cardiovascular problems but if she were hypotensive gut blood flow may be low There is no umbilical
Nicholas D Embleton BSC (Hons) MBBS (Hons) MD FRCPCH is Consultant in
Neonatal Medicine at Newcastle Neonatal Service Royal Victoria
Infirmary Newcastle upon Tyne NE1 4LP UK
Should you start feeds at a day of age
alice was born following spontaneous labour at 30 weeksrsquo
gestation she weighed 1300 g and is now 18 h old she was
briefly ventilated and then extubated to continuous positive
airway pressure 12 h ago in 35 oxygen she has had caffeine
citrate but still has intermittent episodes of self-correcting
apnoea she was commenced on iv 10 dextrose but this was
replaced by a parenteral amino acid solution (referred to as
lsquotPnrsquo) along with intralipid at 0900 this morning serum glucose
is 11 mmoll and blood pressure is 42 systolic
PaeDiatrics anD cHilD HealtH 184 20
arterial catheter in situ but there is no good evidence that this should delay the decision to start feeds Her glucose is high but this is quite common in a baby like this Could this be a sign of sepsis Caffeine does not affect the incidence of NEC2 The great-est risk factor for NEC in this case is prematurity
What else might be found on examination
Up until 24 h ago she was swallowing large amounts of amniotic fluid What will have changed since then
General examination should confirm peripheral perfusion lsquogestaltrsquo view (does she look lsquowellrsquo) and cardiovascular status lsquoBowel soundsrsquo are not usually helpful
The most important variable likely to affect gut perfusion is the arterial duct Precordial lsquoheaversquo and a loud murmur are sug-gestive but it is possible to have a significant ductal shunt in a baby with a normal examination Cardiac ultrasound will con-firm this diagnosis It might be better to treat a large shunt first with indometacin and to delay starting feeds for a further 24 h
It is not possible to assess gut perfusion clinically but normal perfusion elsewhere (adequate urine output usually indicates adequate renal perfusion) would be reassuring Most preterm babies have a few abdominal lsquoloopsrsquo visible but a distended abdomen with many palpable loops suggests ileus This might be secondary to sepsis or poor gut blood flow Preterm babies do not pass much meconium in the first 24ndash48 h
Balance of risks between starting and withholding feeds
Alice requires 35ndash4 gkgd of protein and 120 kcalkgd to grow3 This will initially be provided parenterally Delaying feeds increases the risk of gut villous atrophy and prolongs the need for lsquototal parenteral nutrition (TPN)rsquo TPN requires intravenous access and so increases the risk of sepsis and when prolonged use is required combined with the lack of enteral feeding may result in hepatic impairment
Delaying feeds may allow a gut that has been chronically under-perfused to re-establish more normal perfusion although normal gut endocrine function digestive enzyme upregulation and motility require a source of intraluminal nutrients1 A recent study suggested benefit from delaying the introduction of feeds4 but methodologi-cal problems exist5 Although a Cochrane meta-analysis suggested no benefit only two studies were included6 A large UK-based trial is examining the effect of early or late feeding in preterm infants who were born growth retarded following identification of antena-tal absent or reversed end diastolic flow in the umbilical artery7
When starting feeds what volume should be used
There are no good data to guide this decision We start with 24 mlkg (1 mlkgh) and then increase by this amount each day Most babies achieve full enteral feeds (ge150 mlkgd) by a week of age Feeding guidelines improve the outcome8 Measure-ment or assessment of gastric aspirates is not consistently useful in predicting subsequent feeding intolerance or development of NEC Aspirate volumes equivalent to or sometimes greater than the amount given in the preceding 1ndash2 h are usually normal Most aspirates have a greenish colour Thick bloody or intensely bile-stained aspirates require detailed assessment
0 copy 2008 elsevier ltd all rights reserved
Personal Practice
What else affects decisions and outcome
Feeding success is affected by sepsis and NEC Scrupulous atten-tion should be paid to hand washing and intravenous access and blood sampling should be minimized There is no good evidence to support the routine use of pro-kinetic agents or H2 blockers
The most important clinical intervention affecting the occur-rence of NEC is the use of breast milk9 All efforts should be directed at persuading parents of the benefits and supporting the process Some clinicians delay starting feeds for a further 24 h whilst expressed breast milk becomes available Donor breast milk might be equally efficacious10
RefeRenceS
1 Dorling J Kempley s leaf a Feeding growth restricted preterm
infants with abnormal antenatal Doppler results Arch Dis Child Fetal
Neonatal Ed 2005 90 F359ndash363
2 schmidt B roberts rs Davis P et al caffeine therapy for apnea of
prematurity N Engl J Med 2006 354 2112ndash2121
PaeDiatrics anD cHilD HealtH 184 20
3 embleton nD Pang n cooke rJ Postnatal malnutrition and growth
retardation an inevitable consequence of current recommendations
in preterm infants Pediatrics 2001 107 270ndash273
4 Berseth cl Bisquera Ja Paje VU Prolonging small feeding volumes
early in life decreases the incidence of necrotizing enterocolitis in
very low birth weight infants Pediatrics 2003 111 529ndash534
5 Menon G Boyle eM embleton nD et al introduction of enteral
feeds in preterm infants Pediatrics 2004 114 327ndash328
6 Kennedy Ka tyson Je chamnanvanikij s early versus delayed
initiation of progressive enteral feedings for parenterally fed low
birth weight or preterm infants Cochrane Database Syst Rev 2000
cD001970
7 wwwnpeuoxacukadept
8 Patole sK de Klerk n impact of standardised feeding regimens on
incidence of neonatal necrotising enterocolitis a systematic review
and meta-analysis of observational studies Arch Dis Child Fetal
Neonatal Ed 2005 90 F147ndash151
9 lucas a cole tJ Breast milk and neonatal necrotising enterocolitis
Lancet 1990 336 1519ndash1523
10 Boyd ca Quigley Ma Brocklehurst P Donor breast milk versus
infant formula for preterm infants systematic review and meta-
analysis Arch Dis Child Fetal Neonatal Ed 2007 92 F169ndash175
1 copy 2008 elsevier ltd all rights reserved
self-assessment
Case 1A term male infant born to consanguineous parents is assessed at 24 h of age due to poor feeding profuse yellow watery diar-rhoea and irritability He weighed 32 kg at birth and delivery was uneventful There was no polyhydramnios He has been breastfed since birth On examination he is pale with a non-tender but distended abdomen and reduced bowel sounds His weight is 275 kg and he looks dehydrated Examination is otherwise normal
Initial investigations (normal values in parentheses) showed
sodium 149 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 65 mmollitre (25ndash75)
creatinine 147 μmollitre (40ndash110)
chloride 119 mmollitre (95ndash105)
haemoglobin 172 gdl (140ndash200)
White blood cell count 80 times 109litre (100ndash260)
Platelet count 302 times 109litre (150ndash400)
arterial blood gas
ph 720 (730ndash745)
PcO2 23 kPa (46ndash60)
Bicarbonate 68 mmollitre (220ndash260)
Base excess minus186 mmollitre (minus20 to +20)
lactate 59 mmollitre (06ndash24)
An abdominal X-ray shows distended bowel loops with no intramural thickening or pneumoperitoneum (Figure 1)
He was given nil by mouth and received intravenous fluids and antibiotics His dehydration improved but the metabolic acidosis and diarrhoea persisted despite receiving no enteral feeds and the commencement of total parenteral nutrition Blood and stool cultures were negative
1 Which of the following best describes these results Choose ONE answer ONLY from the followingA Hypernatraemia hyperchloraemic metabolic acidosis
with increased anion gapB Hypernatraemia hyperchloraemic metabolic acidosis
with normal anion gap
Manish Sadarangani BM BCh MA MRCPCH is Clinical Research Fellow
at the Department of Paediatrics University of Oxford Centre for
Clinical Vaccinology and Tropical Medicine Churchill Hospital
Oxford OX3 7LJ UK
Shabna Rajapaksa MB BChir MA MRCPCH is Specialist Registrar in
Paediatrics at the Paediatric Intensive Care Unit John Radcliffe
Hospital Oxford OX3 9DU UK
Nicholas Mann MD FRCP FRCPCH DCH is Consultant Paediatrician at the
Department of Paediatrics Royal Berkshire Hospital Reading RG1
5AN UK
self-assessment
C Hypernatraemic dehydration and compensated metabolic acidosis
D Acute renal failureE Renal tubular acidosis
2 What is the likely diagnosis Choose ONE answer ONLY from the followingA Hirschsprung disease ndash long segmentB Cystic fibrosis with meconium ileusC Microvillus inclusion diseaseD Cowrsquos milk protein intoleranceE Lactose intolerance
3 What is the investigation of choice Choose ONE answer ONLY from the followingA Rectal biopsy with staining for acetylcholine receptorsB Immunoreactive trypsinC Gastrointestinal endoscopy and biopsyD Stool microscopy and cultureE Stool reducing substances
Case 2A 4-year-old boy presents with a 3 d history of jaundice and a florid rash He has had orange urine and there is no change in his stool colour His family originate from Kosovo and have lived in the UK for the last 8 years He has never left the UK There is no history of blood transfusion or sex-ual abuse The grandmother was recently diagnosed with hepatitis B
On examination he is well apyrexial and mildly jaundiced with cervical and axillary lymphadenopathy He has an exten-sive papular rash over the face extremities and trunk (Figure 2) There is 3 cm hepatomegaly with no splenomegaly or ascites Examination is otherwise normal
Figure 1 abdominal X-ray of baby
Paediatrics and child health 184 202 copy 2008 elsevier ltd all rights reserved
self-assessment
Initial investigations are as follows
haemoglobin 110 gdl (113ndash135)
White blood cell count 108 times 109litre (50ndash150)
Platelet count 278 times 109litre (150ndash400)
inr 10 (08ndash12)
aPt ratio 10 (08ndash13)
sodium 140 mmollitre (135ndash145)
Potassium 42 mmollitre (35ndash50)
Urea 56 mmollitre (25ndash75)
creatinine 65 μmollitre (45ndash120)
total bilirubin 66 μmollitre (0ndash15)
conjugated bilirubin 23 μmollitre (0ndash10)
alanine aminotransferase (alt) 2033 iUlitre (0ndash35)
alkaline phosphatase 987 iUlitre (71ndash234)
Gamma-glutamyl transferase (GGt) 870 iUlitre (0ndash51)
1 What is the name of this rash Choose ONE answer ONLY from the followingA Erythema multiformeB Erythema migransC GianottiminusCrosti syndromeD EczemaE Dermatitis herpetiformis
2 What is the most likely diagnosis Choose ONE Answer ONLY from the followingA Autoimmune hepatitisB Hepatitis BC Hepatitis DD Wilson diseaseE Alpha-1 antitrypsin deficiency
3 What is the best means of management Choose ONE answer ONLY from the followingA Isolation until the jaundice disappearsB ImmunosuppressionC Copper chelating agents and genetic counsellingD Patient and family education with consideration of
antiviral agentsE Liver transplantation
Case 3A 10-month-old boy presents with 3 weeks of vomiting and constipation ndash he is passing hard stools every 2ndash3 days He has fallen from the 9th to below the 04th centile in the last 6 weeks He passed meconium within the first 24 h of life On examina-tion he looks pale and there are some dysmorphic features ndash a short nose long philtrum and wide mouth He has normal heart sounds with a grade 3 ejection systolic murmur loudest at the upper right sternal edge Examination is otherwise normal
Initial investigations are as follows
haemoglobin 91 gdl (113ndash141)
total white blood cell count 124 times 109litre (60ndash170)
Platelet count 407 times 109litre (150ndash400)
sodium 144 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 78 mmollitre (25ndash75)
creatinine 78 μmollitre (45ndash120)
albumin 52 glitre (35ndash50)
corrected calcium 384 mmollitre (238ndash263)
Phosphate 167 mmollitre (099ndash157)
1 What is the most likely diagnosis Choose ONE answer ONLY from the followingA HyperparathyroidismB Acute leukaemiaC Williams syndromeD Hypervitaminosis DE Familial hypocalciuric hypercalcaemia
2 Which investigation would be most useful in establishing the diagnosis Choose ONE answer ONLY from the followingA Intact parathyroid hormone assayB Blood filmC Fluorescent in-situ hybridization for 7q1123 deletionD 25-hydroxyvitamin D assayE Urine calciumcreatinine ratio
3 Which of the following treatments would not be suitable for this patient Choose ONE answer ONLY from the followingA Low calcium dietB Normal saline infusionC FurosemideD CorticosteroidsE Bisphosphonates
Case 4A 10-week-old girl presents with a 2-day history of poor feed-ing Her mother has been concerned about weakness since birth She only has a flicker of movement in the arms none in the legs and has a weak cry She has been passing urine and opening her bowels normally She was born at full term by normal delivery and did not require any resuscitation at birth Normal fetal movements were felt antenatally and there was no polyhydramnios She is the first child of non- consanguineous parents and there is no significant family his-tory On examination she is alert and fixing and following appropriately She has a weak cry and a weak suck There is reduced central and peripheral tone with marked head lag
Figure 2 rash found on examination
Paediatrics and child health 184 203 copy 2008 elsevier ltd all rights reserved
self-assessment
Muscle power is grade 3 out of 5 in the arms and legs There is no muscle or tongue fasciculation and she has absent reflexes throughout The remainder of the examination is normal
Electromyogram shows irregular polyphasic motor unit potentials with marked instability consistent with a dener-vating and re-innervating process (Figure 3)
1 Which of the following additional investigations may be helpful Choose ONE answer ONLY from the followingA Nerve conduction studiesB Creatine kinase assayC Muscle biopsyD SMN1 gene analysisE All of the above
2 What is the most likely cause of this childrsquos symptoms Choose ONE answer ONLY from the followingA Congenital myotonic dystrophyB Duchenne muscular dystrophyC PraderminusWilli syndromeD Spinal muscular atrophyE Mitochondrial myopathy
3 What is the mode of inheritance of this disease Choose ONE answer ONLY from the followingA X-linked recessiveB Autosomal recessiveC Autosomal dominantD MitochondrialE Sporadic
Case 5A 13-year-old girl presents with a 3-week history of fever up to 40degC night sweats and headache She has a reduced appetite with some weight loss She has no other specific symptoms She was on holiday in China 7 months ago On examination she looks well and has a temperature of 387degC There is no lymphadenopathy and no rashes Examination is entirely normal
Results of investigations are as follows
haemoglobin 126 gdl (120ndash160)
total white blood cell count 132 times 109litre (43ndash108)
neutrophil count 115 times 109litre (25ndash75)
Platelet count 244 times 109litre (150ndash400)
Blood film neutrophilia with left shift
erythrocyte sedimentation rate 63 mmh (1ndash20)
c-reactive protein 219 mglitre (0ndash5)
Blood culture Streptococcus intermedius
from anaerobic bottle only
csf culture negative
Magnetic resonance imaging (MRI) of the brain shows acute frontal sinusitis with a large intracranial frontal extra-dural empyema (Figure 4)
1 Which of the following would be appropriate management Choose ONE answer ONLY from the followingA A 12-week course of intravenous antibioticsB Drainage of the frontal sinus followed by 2 weeks of
intravenous antibioticsC Drainage of the empyema followed by 2 weeks of
intravenous antibioticsD Drainage of the empyema and the frontal sinus
followed by 2 weeks of oral antibiotics
1151
1152
1153
1154
1155
1156
1157
1158
1159
1200
50ms 1mV
Figure 3 electromyogram recording from the patient Figure 4 Parasagittal section from mri scan of patient
Paediatrics and child health 184 204 copy 2008 elsevier ltd all rights reserved
self-assessment
E Drainage of the empyema and the frontal sinus followed by 8 weeks of intravenous antibiotics
2 Streptococcus intermedius is a potential pathogen in which of the following infections Choose ONE answer ONLY from the followingA Liver abscessB Urinary tract infectionC MeningitisD Thoracic empyemaE Pneumonia
3 Which of the following statements regarding lsquopyrexia of unknown originrsquo in children is false Choose ONE answer ONLY from the followingA Malignancy is the underlying pathology in 5ndash15 of
casesB An aetiology will be found in over 90 of casesC The most common cause is infectionD A rheumatological cause is found in 10ndash20 of casesE Familial Mediterranean fever can occur in children of
non-Mediterranean ethnicity
Answers
Case 11 AThe anion gap is a useful tool to differentiate the causes of a metabolic acidosis It is calculated by the equation
Anion gap = [Na K ] [Cl HCO ]3+ + minus minus+ minus +
It represents the effect of unmeasured anions on the plasma pH and is normally 10ndash18 mmollitre
2 CMicrovillus inclusion disease is a severe autosomal recessive enteropathy that is typically apparent within hours or days after birth It is the second most common cause of protracted diarrhoea in the newborn after infectious causes It is characterized by severe yellow watery diarrhoea and malabsorption due to hypoplasia andor atrophy of the villi of the small intestine secondary to an inherited defect in the brush border membrane This results in severe dehydration malnutrition and metabolic acidosis due to bicarbonate loss from the gut
3 CDiagnosis of microvillus inclusion disease is made on small bowel biopsy Electron microscopy findings are of intracellular brush border inclusions and densely packed apical cytoplasmic vesicular bodies indicating microvillous atrophy There is no cure Treatment is supportive with total parenteral nutrition and consideration of small bowel transplantation
Further reAding
Goulet O ruemmele f causes and management of intestinal failure
in children Gastroenterology 2006 130(suppl 1) s16ndash28
rhoads Jm Vogler rc lacey sr et al microvillus inclusion disease
In vitro jejunal electrolyte transport Gastroenterology 1991
100 811ndash817
Case 21 CGianottindashCrosti syndrome is a distinct self-limiting rash commonly associated with viral infections in children between 2 and 6 years of age It presents as multiple pink to redminusbrown papules or papulovesicles which may be pruritic and can become confluent Gianotti and Crosti initially described the exanthema as associated with hepatitis B virus and they termed it papular acrodermatitis of childhood It can occur in several viral diseases eg hepatitis A B and C coxsackie viruses and cytomegalovirus
2 BHepatitis is a syndrome characterized by inflammation or injury of liver cells which may develop into cell necrosis and subsequently fibrosis andor cirrhosis Biochemically there are raised liver enzymes The degree of transaminase elevation does not correlate with the severity of the disease process Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of viral hepatitis
3 DHepatitis B infection is transmitted via blood sexually or vertically Infection may be acute or chronic Diagnostic markers are the presence of surface antigen (HBsAg) and HBV DNA The presence of e antigen (HBeAg) indicates high infectivity Infected newborns have a 95 risk of becoming carriers this risk decreases with infection acquired later in childhood Approximately 15ndash25 of HBV carriers will die from cirrhosis or hepatocellular carcinoma Extrahepatic findings are more common in older children and include membranous glomerulonephritis and GianottiminusCrosti syndrome Fulminant hepatic failure occurs in severe cases resulting in persistent jaundice encephalopathy and coagulopathy Management includes counselling family members monitoring for ongoing liver disease and consideration of antiviral therapy
Further reAding
Brandt O abeck d Gianotti r Burgdorf W Gianotti crosti
syndrome J Am Acad Dermatol 2006 54 136ndash145
slowik mK Jhaveri r hepatitis B and c viruses in infants and
young children Semin Pediatr Infect Dis 2005 16 296ndash305
Case 31 CHypercalcaemia is uncommon in infancy The most common symptoms in this age group are irritability vomiting and constipation It may be a manifestation of Williams syndrome vitamin D or calcium excess as well as disorders associated with reduced bone formation such as hypophosphatasia or increased bone resorption such as malignancy Occasionally
Paediatrics and child health 184 205 copy 2008 elsevier ltd all rights reserved
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-
SympoSium neonatology
4 Costeloe K Hennessy e gibson at marlow n Wilkinson aR for the
epiCure Study group the epiCure study outcomes to discharge
from hospital for infants born at the threshold of viability Pediatrics
2000 196 659ndash671
5 CeSDi project 2728 available from wwwcemachorguk
publicationsp2728mainreportpdf
6 parry g tucker J tarnow-mordi W for the uK neonatal Staffing
Study Collaborative group CRiB ii an update of the clinical risk
index for babies score Lancet 2003 361 1789ndash1791
7 Richardson DK Corcoran JD escobar gJ et al Snap-ii and Snappe-ii
simplified newborn illness severity and mortality risk scores
J Pediatr 2001 138 92ndash100
8 Wyatt JS gluckman pD liu py et al CoolCap Study group
Determinants of outcomes after head cooling for neonatal
encephalopathy Pediatrics 2007 119 912ndash921
9 yager Jy armstrong ea Jaharus C Saucier Dm Wirrell eC preventing
hyperthermia decreases brain damage following neonatal-ischemic
seizures Brain Res 2004 1011 48ndash57
10 Harned Jr HS Herrington Rt Ferreiro Ji the effects of immersion
and temperature on respiration in newborn lambs Pediatrics 1970
45 598ndash605
11 laptook aR Salhab W Bhaskar B neonatal Research network
admission temperature of low birth weight infants predictors and
associated morbidities Pediatrics 2007 119 e643ndash649
12 lyon aJ pikaar me Badger p mcintosh n temperature control in
infants less than 1000g birthweight in the first 5 days of life Arch
Dis Child 1997 76 F47ndash50
13 Vohra S Roberts RS Zhang B Janes m Schmidt B Heat loss
prevention (Help) in the delivery room a randomized controlled
trial of polyethylene occlusive skin wrapping in very preterm infants
J Pediatr 2004 145 750ndash753
14 lyon aJ Stenson B Cold comfort for babies Arch Dis Child Fetal
Neonatal Ed 2004 89 F93ndash94
15 Stothers JK Head insulation and heat loss in the newborn Arch Dis
Child 1981 56 530ndash534
16 newton t Watkinson m preventing hypothermia at birth in
preterm babies at a cost of overheating some Arch Dis Child Fetal
Neonatal Ed 2003 88 F256
17 Smith Cl Quine D mcCrosson F armstrong l lyon a Stenson B
Changes in body temperature after birth in preterm infants
stabilised in polythene bags Arch Dis Child Fetal Neonatal Ed 2005
90 F444
18 mcCall em alderdice Fa Halliday Hl Jenkins Jg Vohra S
interventions to prevent hypothermia at birth in preterm andor low
birthweight babies Cochrane Database of Systematic Reviews 2005
issue 1 art noCD004210 doi10100214651858CD004210pub2
19 meyer mp Bold gt admission temperatures following radiant
warmer or incubator transport for preterm infants lt 28 weeks
a randomised study Arch Dis Child Fetal Neonatal Ed 2007 92
F295ndash297
20 Carmichael a mcCullough S Kempley St Critical dependence of
acetate thermal mattress on gel activation temperature Arch Dis
Child Fetal Neonatal Ed 2007 92 F44ndash45
21 Hey en the care of babies in incubators in gairdner D Hull D
eds Recent advances in paediatrics 4th edn london J amp a
Churchill 1971 p 171ndash216
22 Whitelaw a Heisterkamp g Sleath K acolet D Richard m Skin-to-
skin contact for very low birthweight infants and their mothers Arch
Dis Child 1988 63 1377ndash1381
paeDiatRiCS anD CHilD HealtH 184 15
23 Bauer K pyper a Sperling p uhrig C Versmold H effects of
gestational and postnatal age on body temperature oxygen
consumption and activity during early skin-to-skin contact between
preterm infants of 25ndash30-week gestation and their mothers Pediatr
Res 1998 44 247ndash251
24 Hey en Katz g orsquoConnell B the total thermal insulation of the
newborn baby J Physiol 1970 207 683ndash689
25 Hey en temperature regulation in sick infants in tinker J Rapin m
eds Care of the Critically ill patient Berlin Springer 1983 p
1013ndash1029
26 leBlanc mH Relative efficacy of an incubator and an open warmer
in producing thermoneutrality for the small premature infant
Pediatrics 1982 69 439ndash445
27 meyer mp payton mJ Salmon a Hutchinson C deKlerk a
a clinical comparison of radiant warmer and incubator care for
preterm infants from birth to 1800grms Pediatrics 2001 108
395ndash401
28 Silverman Wa Blanc Wa effect of humidity on survival of newly
born premature infants Pediatrics 1957 20 477ndash487
29 Hammarlund K Sedin g transepidermal water loss in newborn
infants iii relation to gestational age Acta Paediatr Scand 1979
68 795ndash801
30 Hammerlund K Stroumlmberg B Sedin g Heat loss from the skin of
preterm and fullterm newborn infants during the first weeks after
birth Biol Neonate 1986 50 1ndash10
31 Kalia yn nonata lB lund CH guy RH Development of skin
barrier function in premature infants J Invest Dermatol 1998 111
320ndash326
32 Kjartansson S arsan S Hammarlund K Sjoumlrs g Sedin g Water loss
from the skin of term and preterm infants nursed under a radiant
heater Pediatr Res 1995 37 233ndash238
33 mok Q Bass Ca Ducker Da mcintosh n temperature instability
during nursing procedures in preterm neonates Arch Dis Child
1991 66 783ndash786
34 mancini aJ Sookdeo-Drost S madison KC Smoller BR lane at
Semipermeable dressings improve epidermal barrier function in
premature infants Pediatr Res 1994 36 306ndash314
35 Donahue ml phelps Dl Richter Se Davis Jm a semipermeable skin
dressing for extremely low birth weight infants J Perinatol 1996 16
20ndash26
36 nopper aJ Horii Ka Sookdeo-Drost S Wang tH mancini aJ lane at
topical ointment therapy benefits premature infants J Pediatr 1996
128 660ndash669
37 pabst RC Starr Kp Qaiyumi S Schwalbe RS gewold iH the effect
of application of aquaphor on skin condition fluid requirements
and bacterial colonization in very low birth weight infants
J Perinatol 1999 19 278ndash283
38 Kjartansson S Hammarlund K Sedin g insensible water loss from
the skin during phototherapy in term and preterm infants Acta
Paediatr 1992 81 764ndash768
39 grunhagen DJ de Boer mg de Beaufort aJ Walther FJ
transepidermal water loss during halogen spotlight phototherapy in
preterm infants Pediatr Res 2002 51 402ndash405
40 Hanley K Jiand y elias pm Feingold KR Williams ml acceleration
of barrier ontogenesis in vitro through air exposure Pediatr Res
1997 41 293ndash299
41 Denda m Sato J masuda y et al exposure to a dry environment
enhances epidermal permeability barrier function J Invest Dermatol
1998 111 858ndash863
9 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
42 Aringgren J Sjoumlrs g Sedin g ambient humidity influences the rate of
skin barrier maturation in extremely preterm infants J Pediatr 2006
148 613ndash617
43 Sinclair l Sinn J Higher versus lower humidity for the prevention of
morbidity and mortality in preterm infants in incubators (protocol)
Cochrane Database Syst Rev 2007 issue 2 art noCD006472
doi10100214651858
44 Hey en Katz g the optimum thermal environment for naked
babies Arch Dis Child 1970 45 328ndash334
45 Sauer pJJ Dane HJ Visser HKa new standards for neutral thermal
environment of healthy very low birthweight infants in week one of
life Arch Dis Child 1984 59 18ndash22
46 Dollberg S Xi y Donnelly mm a noninvasive alternative to rectal
thermometry for continuous measurement of core temperature in
the piglet Pediatr Res 1993 34 512ndash517
47 messaritakis J anagnostakis D laskari H Katerelos C Rectal-skin
temperature difference in septicaemic newborn infants Arch Dis
Child 1990 65 380ndash382
paeDiatRiCS anD CHilD HealtH 184 16
Practice points
bull Hypothermia in the newborn infant is associated with adverse
outcome
bull Despite improvements in technology the preterm baby is still
at high risk of hypothermia immediately after delivery
bull prevention of evaporative heat losses eliminates hypothermia
at resuscitation
bull High evaporative fluid losses must be prevented if the baby
is nursed under a radiant heater
bull more studies are needed to determine the optimum
management after delivery and to show if reducing
transepidermal water loss has an effect on the rate of skin
maturation
bull Continuous monitoring and display of a central and peripheral
temperature gives early warning of developing cold stress
0 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemiaJ m Hawdon
Abstractat birth the newborn baby undergoes many adaptive changes to inde-
pendent extrauterine life these include the changes of metabolic adap-
tation which must be understood in order to identify and manage the
conditions in which metabolic adaptation is delayed impaired or fails
resulting in low levels of glucose and other metabolic fuels which in turn
affect neonatal neurological function and if prolonged and severe cause
potential adverse outcome Babies identified as at risk of impaired met-
abolic adaptation must undergo clinical monitoring including accurate
blood glucose monitoring tailored to their condition Babies who present
with abnormal clinical signs in association with a low blood glucose level
must be investigated for underlying cause and treated promptly preven-
tion and treatment of clinically significant hypoglycaemia must be planned
to avoid compromising successful establishment of breast feeding
Keywords alternative fuels blood glucose breast feeding neonatal
metabolic adaptation operational thresholds risk factors
Introduction
At birth the newborn baby undergoes many adaptive changes to independent extrauterine life These include the changes of met-abolic adaptation essential to ensure energy provision to vital organs and then to sustain growth and further development The changes involved in metabolic adaptation must be understood in order to identify and manage the conditions in which metabolic adaptation is delayed impaired or fails The clinical outcome of these circumstances is usually referred to with the single short-hand diagnostic term lsquoneonatal hypoglycaemiarsquo However as will be illustrated in this article it is not appropriate to ascribe a diagnostic label to neonatal hypoglycaemia first because glucose is not the only fuel in the neonatersquos fuel economy and second because hypoglycaemia is the consequence of a number of vari-ous underlying disorders and thus does not in itself warrant a diagnostic label
There have been extensive studies of metabolic adaptation in human neonates and neonatal non-human mammals The latter studies have identified those mammals most similar to humans
J M Hawdon MA MBBS MRCP FRCPCH PhD is Consultant Neonatologist and
Honorary Senior Lecturer at UCL EGA Institute for Womenrsquos Health
Elizabeth Garrett Anderson and Obstetric Hospital University College
London Hospitals NHS Foundation Trust Huntley Street London UK
paeDiatRiCS anD CHilD HealtH 184 161
in terms of metabolic adaptation and sought to compare nutri-tionally comparable time frames eg suckling versus weaning periods Whilst the processes of metabolic adaptation are well described in term and preterm human neonates there are few if any clinical studies in human neonates of sufficient rigour to provide evidence for the circumstances in which brain injury may occur and thus it is not possible to provide evidence-based guide-lines for the prevention and management of clinically significant hypoglycaemia Therefore recommendations in this article and in the referenced review articles by recognized experts remain pragmatic and urge clinicians to individualize management for each baby placing heavy emphasis on careful clinical evaluation rather than single numerical definitions of brain-injuring hypogly-caemia and on detecting and treating underlying pathologies1ndash6
Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
During intrauterine life the fetus receives via the placenta a con-stant supply of nutrients initially for growth but in the third tri-mester also for storage Glucose crosses the healthy placenta at a rate of approximately 5 mgkgmin In addition to that required for basal fetal metabolism glucose is converted to glycogen which is stored in the liver cardiac muscle and central nervous system In the third trimester excess glucose is converted to tri-glycerides which are stored in adipose tissue
Insulin is an important fetal hormone to ensure glucose and other substrates are utilized for growth and storage but in nor-mal circumstances insulin is not required for fetal glucose con-trol The exception is for the infant of the mother with poorly controlled diabetes when transfer of glucose across the placenta is at a higher rate driven by the maternalndashfetal concentration gra-dient This results in increased insulin secretion excess growth and increased storage of glycogen and adipose tissue (macroso-mia) along with increased risk of intracellular hypoxia
Conversely in the fetus affected by severe placental insuffi-ciency transfer of glucose and other nutrients across the placenta is at a lower rate and the fetus is required to metabolize first its own fuel stores and then structural proteins (eg in muscle) to ensure energy delivery to the vital organs assisted by the redis-tribution of blood flow to these organs Should placental function deteriorate further these adaptive responses fail Fetal hypogly-caemia has been described in these circumstances78
When placental nutrition abruptly ceases at birth the healthy neonate is dependent upon endocrine changes to initiate meta-bolic adaptation Insulin levels fall steadily and the action of any residual circulating insulin is overcome by the surge of the coun-ter-regulatory hormones glucagon and the catecholamines This change in the balance of glucoregulatory hormones induces the activity of key enzymes for glycogenolysis (release of glucose from glycogen stores) gluconeogenesis (production of glucose from precursors including glycerol and amino acids) lipolysis (release of free fatty acids and glycerol from adipose tissue stores) and beta-oxidation of fatty acids to produce ketone bodies910 If fasting is prolonged structural protein is broken down to release gluconeogenic amino acids Other than lipolysis and proteolysis all of these processes take place in the liver Glycogenolysis also takes place in cardiac muscle and the central nervous system providing immediate energy (in the form of glucose or lactate)
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
at this crucial time411 Clearly during this catabolic phase of immediate postnatal nutrition prior to the establishment of suck-ling feeds provision of energy for vital organ function is at the expense of growth and fuel storage
The postnatal metabolic transition is characterized by low cir-culating blood glucose concentrations compared to those of older infants and children often for a number of days12 This is almost always of no pathological significance for a number of reasons including differences in the function and metabolic requirements of the brain and importantly the production and utilization of alter-native fuels lactate and ketone bodies which are in plentiful supply in the neonate341213ndash20 An important finding from clinical studies and of clinical relevance to those caring for mothers and babies is that in all groups of infants studied to date those who are breast fed have higher circulating ketone body levels than those who are formula fed even after correcting for blood glucose levels102122
There are circumstances however when hypoglycaemia is severe and prolonged and conditions when alternative fuel pro-duction is also impaired or fails In these circumstances low blood glucose levels do acquire clinical significance The key metabolic processes and the risk factors for impaired metabolic adaptation are summarized in Table 1
Metabolic changes at birth ndash key hormones and metabolic processes and risk factors for impaired metabolic adaptation
Postnatal metabolic
changes
Risk factors
Hormones
insulin falls neonatal hyperinsulinism ndash infant of
diabetic mother or idiopathic
glucagon surge possibly blunted by iv glucose or
formula feeds
Catecholamine surge maternal beta-blocker medication
(Cortisol ndash weak effect) (pituitary or adrenal insufficiency)
Metabolic processes
glygogenolysis preterm intrauterine growth
restriction (iugR) ndash reduced stores
perinatal hypoxia-ischaemia ndash stores
utilized
Hyperinsulinism
maternal beta-blocker medication
glycogen storage disorders
gluconeogenesis Hyperinsulinism
maternal beta-blocker medication
Hepatic dysfunction
Very rare inborn errors of metabolism
lipolysis preterm iugR ndash reduced stores
Hyperinsulinism
maternal beta-blocker medication
Ketogenesis Defects of beta-oxidation of fatty
acids
Hepatic dysfunction
Table 1
paeDiatRiCS anD CHilD HealtH 184 16
Impaired metabolic adaptation
Risk factors for impaired metabolic adaptation vary and may be related to any of the following reduced body fuel stores failure of the normal endocrine changes at birth systemic illnesses which impede function of the liver where the key metabolic processes occur or rarely inborn errors of metabolism (see Table 1)
It is well recognized that significant hypoglycaemia will result in a reduced level of consciousness andor fits However it is always important to be alert for detect and treat an underlying pathology which could be causing both the hypoglycaemia and the abnormal signs Often abnormal signs and hypoglycaemia are co-morbidities eg a primary neurological problem causes both abnormal neurological signs and hypoglycaemia secondary to poor feeding For this reason all possible underlying causes for presentation with hypoglycaemia must be considered and investigations planned accordingly Investigations for inborn errors of metabolism and endocrine disorders are most informa-tive if carried out when blood glucose levels are low
There have been extensive efforts to use data from clinical stud-ies of the human neonate to determine the significance of neonatal hypoglycaemia in terms of neurophysiological neurodevelopmental and neuroradiological sequelae However there are major difficul-ties in interpreting these clinical studies as to date these have been flawed by confounding factors such as immaturity placental insuf-ficiency and co-existing complications by heterogeneity of subjects and by failure to take into account protective mechanisms11423 The evidence from both animal and human studies suggests lsquopurersquo hypo-glycaemic brain injury is rare and for hypoglycaemic brain injury to occur there must be co-existing failure of metabolic adaptation such that alternative fuels are not available There is no evidence that lsquotransitionalrsquo hypoglycaemia in the healthy neonate is associated with acute or long term sequelae and indeed even for babies in the at-risk groups on many occasions protective factors will prevail
Diagnosis of clinically significant hypoglycaemia
lsquoNeonatal hypoglycaemiarsquo is a commonly cited diagnosis most often based on a single blood glucose level and using inaccurate methods of measurement and with disregard for the presence or absence of associated clinical signs In the many published texts and local guidelines there is no consistency of approach For this reason a multinational group of experts attempted to examine critically the evidence on which clinical recommendations should be made1 Fol-lowing detailed analysis the authors considered it impossible to define hypoglycaemia as a single blood glucose level and instead suggested operational thresholds and therapeutic goals They con-cluded that low blood glucose levels accompanied by neurological signs should be investigated and treated regardless of the blood glu-cose level They also pragmatically concluded that a blood glucose level below 10 mmollitre should be treated immediately In babies who are at risk of impaired metabolic adaptation but who have no clinical signs it is recommended that interventions to raise blood glucose level are considered if blood glucose levels are persistently below 20 mmollitre For sick and very low birthweight babies who are likely to have a requirement for intravenous glucose there should be a lsquotherapeutic goalrsquo to maintain blood glucose levels above 25 mmollitre Where there is known hyperinsulinism (a very high-risk condition characterized by high intravenous glucose
2 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
requirements to maintain normoglycaemia) an operational thresh-old and therapeutic goal of 35 mmollitre has been proposed24
Finally there must be careful consideration of the infant of the diabetic mother In extreme and rare cases there may be signifi-cant but transient hyperinsulinism and in these cases the thera-peutic goal must be 35 mmollitre More commonly babies whose mothersrsquo diabetes has been well controlled will have normal lsquotran-sitional hypoglycaemiarsquo or slightly delayed metabolic adaptation while insulin levels fall postnatally There must be careful and repeated clinical assessment including blood glucose monitoring For infants of diabetic mothers who have no evidence of signifi-cant hyperinsulinism and no abnormal clinical signs there is no evidence that the operational threshold for hyperinsulinism must be applied Indeed to do so would result in separation of large numbers of healthy babies from their mothers with the conse-quent impact upon breast feeding and resource allocation25
The operational thresholds for various groups of babies are summarized in Table 2
The guidance relating to operational thresholds is predicated upon the accurate measurement of blood glucose levels It is now well known that the commonly used reagent strips are insufficiently accurate to diagnose hypoglycaemia and monitor at-risk infants and there must be access to equipment which allows immediate and accurate determination of blood glucose levels1426ndash28
Blood glucose monitoring
An accurate method for blood glucose monitoring must be employed as described above The sample should be free flowing venous or from a warm heel such that the blood flows freely without squeezing
Blood of high haematocrit often yields low blood glucose lev-els because of dilution of glucose by red cell water However this is also clinically relevant because polycythaemia is itself a high-risk situation Therefore in polycythaemic infants both the haematocrit and blood glucose level must be monitored and both acted upon accordingly
Operational thresholds for blood glucose levels in the management of babies at risk of impaired metabolic adaptation124
Clinical condition Blood glucose level at which
to consider intervention and
therapeutic goal
all at-risk babies lt10 mmollitre
abnormal neurological
signs
intervene regardless of blood
glucose levelSystematically unwell baby therapeutic goal of 25 mmollitre
at-risk babies no abnormal
neurological signs
persistently lt20 mmollitre
Hyperinsulinism 35 mmollitre
Table 2
paeDiatRiCS anD CHilD HealtH 184 163
Only babies in at-risk groups or babies who have abnormal neurological signs should be subjected to blood glucose monitor-ing (Table 3)
It is important not to commence blood glucose monitoring too soon after birth as to do so would fail to differentiate the baby with incipient hypoglycaemia from the baby undergoing the nor-mal postnatal fall in blood glucose level It is recommended in the otherwise healthy but at-risk baby to wait until around 3 h after birth to make the first blood glucose estimation2528 In prac-tice this is usually before the second feed assuming best practice of offering a baby a breast (or if necessary formula feed) imme-diately after birth Clearly if the baby is unwell or has abnormal clinical signs in the first 3 h they will be treated according to clinical condition which will include intravenous fluids and the therapeutic goal described above would apply
Similarly the temptation to measure blood glucose level shortly (within 2 h) after intravenous glucose has been discon-tinued must be avoided In this circumstance as at birth blood glucose levels fall and then subsequently rise in response to coun-ter-regulation It is this effective rise which must be assessed by blood glucose measurement at least 2 h after a change is made (provided the baby remains clinically well)
Blood glucose levels rise after a feed and fall to a nadir before the subsequent feed As our concern is the lowest blood glucose level during the feed cycle and as this measurement may assist in determining best feed frequency it is important that pre-feed blood glucose concentration is measured There is no clinical value in measuring a post-feed blood glucose level as this may be falsely reassuring and this practice subjects babies to more frequent heel pricks or venesections than is necessary
Finally consideration must be given to when to discontinue blood glucose monitoring This will depend upon the babyrsquos clin-ical condition feeding pattern and underlying disorder or risk factors for impaired metabolic adaptation
Prevention and management of clinically significant hypoglycaemia
In babies at risk of clinically significant hypoglycaemia and who are well enough to tolerate enteral feeds milk feeds are the
At-risk babies for whom blood glucose monitoring is recommended
abnormal neurological signs
Systemically unwell eg suspected or proven infection
hypoxicndashischaemic encephalopathy
preterm (lt 37 weeks)
intrauterine growth restriction (lt 2nd centile and any baby with
signs of wasting)
infant of diabetic mother
polycythaemia
maternal beta-blocker medication
Suspected hyperinsulinism
Suspected inborn error of metabolism or endocrine disorder
Table 3
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
mainstay of prevention For babies who are able to feed orally breast feeding should be first choice and there must be maximal support for the mother to do so This is a key clinical priority for midwives and paediatricians
If there are concerns regarding adequacy of breast feeding to prevent hypoglycaemia the mother should be encouraged to commence expression of milk from very soon after birth If there is insufficient breast milk to prevent babies reaching the opera-tional thresholds described above there should be judicious use of formula milk using only the smallest amount required to keep the babyrsquos glucose in the required range Formula milk in exces-sive quantities has been demonstrated to suppress normal meta-bolic adaptation2122
In babies for whom early enteral feeds are not appropriate or not tolerated or for whom enteral feeding does not prevent blood glucose level falling below operational thresholds intravenous glucose infusion at rates around 4ndash5 mgkgmin (58ndash72 mlkgd of 10 dextrose) are usually sufficient to prevent hypoglycae-mia If blood glucose levels remain below therapeutic goals the rate of infusion may be steadily increased Excess glucose infu-sion over and above that required to maintain the therapeutic goal will stimulate insulin and there is a risk of rebound hypo-glycaemia if high rate glucose infusions are too rapidly reduced Milk feeds if tolerated should be continued if intravenous glu-cose is commenced
If infused volume of glucose solution becomes excessive in order to maintain therapeutic goals or if fluid restriction must be applied more concentrated glucose concentrations must be infused through a central venous line This is particularly rel-evant to the hyperinsulinaemic baby in whom glucose infusion rates in excess of 8ndash10 mgkgmin are required to maintain ther-apeutic goals There is a high risk of severe and brain-damaging hypoglycaemia if treatment is delayed or fails to raise blood glu-cose levels and management of these babies requires consulta-tion with or referral to a specialist centre24
If there is presentation of hypoglycaemia with abnormal clinical signs or a very low blood glucose level (less than 1 mmollitre) this mandates urgent treatment with intravenous glucose The rates of glucose infusion described above are usually sufficient to bring the blood glucose level rapidly to the therapeutic goal without a bolus of glucose being necessary In fact a bolus dose of glucose will result in a peak blood glucose level and then an insulin surge making subsequent management problematical This is minimized by the use of a lsquomini-bolusrsquo should a bolus of glucose be required ndash 200 mg glucosekg (2 mlkg of 10 dextrose)28 Indications for mini-bolus are infants presenting with fits or coma or an lsquounre-cordablersquo or zero blood glucose level A mini-bolus should always be followed with glucose infusion or an increased glucose infusion rate if a baby already receiving intravenous glucose has required a mini-bolus
The temptation to supplement enteral feeds with glucose polymers and energy supplements (eg Duocal) or to use oral glucose gels or solutions (eg Hypostop) should be avoided as this carries a risk of necrotizing enterocolitis is likely to suppress normal metabolic adaptation and will suppress the appetite of the baby for effective oral feeding
Finally there are additional medications which may be employed in specific circumstances (Table 4) More detailed descriptions are given elsewhere242728 Babies who have hypoglycaemia which
paeDiatRiCS anD CHilD HealtH 184 164
is difficult to control by the measures described above and who require these additional treatments should be cared for in a centre which has expertise in metabolic and endocrinological conditions
Summary
Much controversy and confusion has surrounded neonatal hypo-glycaemia but this usually arises as a result of failure to under-stand the processes of normal metabolic adaptation and the fact that hypoglycaemia is a presenting sign rather than a diagnosis in itself Plans for investigation and management must be based upon the most likely underlying cause of impaired metabolic adaptation and take into account the clinical condition of the baby This is counter to the current trend to propose rigid pro-tocols and algorithms and re-introduces the value of detailed clinical evaluation and decision making The mainstay of man-agement is close clinical observation of vulnerable infants and energy provision tailored to their individual needs whilst avoid-ing excessively invasive management (namely unnecessary sep-aration of mother and baby routine or excessive formula milk supplementation or intravenous glucose administration) which themselves inhibit protective metabolic responses and impede successful establishment of breast feeding
ReFeRenCeS
1 Cornblath m Hawdon Jm Williams aF et al Controversies regarding
definition of neonatal hypoglycemia Suggested operational
thresholds Pediatrics 2000 105 1141ndash1145
2 Cornblath m ichord R Hypoglycemia in the neonate Semin
Perinatol 2000 24 136ndash149
3 Vannucci RC Vannucci SJ Hypoglycaemic brain injury Semin
Neonatol 2001 6 147ndash155
4 Rozance pJ Hay WW Hypoglycaemia in newborn infants features
associated with adverse outcomes Biol Neonate 2006 90 74ndash86
5 Hawdon Jm Hypoglycaemia in newborn infants defining the
features associated with adverse outcomes ndash a challenging remit
Biol Neonate 2006 90 87ndash88
6 Williams aF neonatal hypoglycaemia clinical and legal aspects
Semin Fetal Neonatal Med 2005 10 363ndash368
7 Soothill pW nicolaides KH Campbell S prenatal asphyxia
hyperlacticaemia hypoglycaemia and erythroblastosis in growth
retarded fetuses BMJ 1987 294 1051ndash1053
Additional medication in specific conditions (if these are required there must also be referral to a specialist centre)
Medication Indication
glucagon intramuscular bolus dose of 200 μgkg
transient rise in blood glucose level eg
when difficulty re-siting intravenous infusion
Diazoxide Hyperinsulinism
Hydorcortisone pituitary or adrenal insufficiency
Table 4
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
8 Hawdon Jm Ward platt mp mcphail S Cameron H Walkinshaw Sa
prediction of impaired metabolic adaptation by antenatal Doppler
studies in small for gestational age fetuses Arch Dis Child 1992
67 787ndash792
9 Deshpande S Hawdon Jm et al adaptation to extrauterine life in
Rodeck C Whittle m eds Fetal medicine Basic Science and Clinical
practice edinburgh Churchill livingstone 1999
10 Ward platt m Deshpande S metabolic adaptation at birth Semin
Fetal Neonatal Med 2005 10 341ndash350
11 eyre Ja Stuart ag Forsyth RJ Heaviside D Bartlett K glucose
export from the brain in man evidence for a role for astrocytic
glycogen as a reservoir of glucose for neural metabolism Brain Res
1994 28 349ndash352
12 Hawdon Jm Ward platt mp aynsley-green a patterns of metabolic
adaptation for preterm and term infants in the first neonatal week
Arch Dis Child 1992 67 357ndash365
13 Hawdon Jm Ward platt mp aynsley-green a prevention and
management of neonatal hypoglycaemia Arch Dis Child Fetal
Neonatal Ed 1994 70 F60ndash64
14 Hawdon Jm Hypoglycaemia and the neonatal brain Eur J Paediatr
1999 158 S9ndash12
15 massieu l Haces ml montiel t Hernaacutendez-Fonseca K acetoacetate
protects hippocampal neurons against glutamate-mediated neuronal
damage during glycolysis inhibition Neuroscience 2003 120
365ndash378
16 yamada Ka Rensing n thio ll Ketogenic diet reduces
hypoglycaemia-induced neuronal death in young rats Neurosci Lett
2005 385 210ndash214
17 nehlig a Brain uptake and metabolism of ketone bodies in animal
models Prostaglandins Leukot Essent Fatty Acids 2004 70
265ndash275
18 Hernaacutendez mJ Vannucci RC Salcedo a Brennan RW Cerebral blood
flow and metabolism during hypoglycemia in newborn dogs
J Neurochem 1980 35 622ndash628
19 Vannucci RC nardis ee Vannucci SJ Campbell pa Cerebral
carbohydrate and energy metabolism during hypoglycaemia in
newborn dogs Am J Physiol 1981 256 H1659ndashH1666
20 anwar m Vannucci RC autoradiographic determination of regional
cerebral blood flow during hypoglycaemia in newborn dogs Pediatr
Res 1988 24 41ndash45
21 Hawdon Jm Williams aF et al Formula supplements given to
healthy breastfed preterm babies inhibit postnatal metabolic
adaptation results of a randomised controlled trial Arch Dis Child
2000 82 a30
paeDiatRiCS anD CHilD HealtH 184 16
22 de Rooy l Hawdon Jm nutritional factors that affect the postnatal
metabolic adaptation of full-term small- and large-for gestational
age infants Pediatrics 2002 109 e42
23 Hawdon Jm Hypoglycaemia and brain injury ndash when neonatal
metabolic adaptation fails in levene m ed Fetal and neonatal
neurology and neurosurgery edinburgh Churchill livingstone in
press
24 Hussain K Congenital hyperinsulinism Semin Fetal Neonatal Med
2005 10 369ndash376
25 acolet D Diabetes in pregnancy Caring for the Baby after Birth
CemaCH 2007 2
26 Hussain K Sharief n the inaccuracy of venous and capillary blood
glucose measurement using reagent strips in the newborn period
and the effect of haematocrit Early Hum Dev 2000 57 111ndash121
27 Hawdon Jm Disorders of blood glucose homeostasis in the neonate
in Rennie Jm ed Robertonrsquos textbook of neonatology 4th edn
edinburgh Churchill livingstone 2005
28 Deshpande S Ward platt mp the investigation and management
of neonatal hypoglycaemia Semin Fetal Neonatal Med 2005 10
351ndash361
Practice points
bull identify risk factors for impaired metabolic adaptation
bull Clinical monitoring including accurate blood glucose
measurement for at-risk babies
bull Feed at-risk babies soon after birth and maintain thermal
homeostasis
bull take first blood glucose level at 3ndash4 h of age
bull intervene in at-risk baby with no clinical signs if two
consecutive blood glucose measurements lt 20 mmollitre
bull intervene in any baby with blood glucose measurement
lt 10 mmollitre
bull intervene in any baby with abnormal clinical signs regardless
of blood glucose level
bull investigate for underlying cause of failure of metabolic
adaptation
bull maintain lactation and breast feeding
5 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Resuscitation of the term and premature babyJonathan Wyllie
Abstractalthough most newly born babies establish normal respiration and
circulation without help up to 1minus2 may require some resuscitation
or stabilization Babies who do not establish adequate regular normal
breathing or who have a heart rate of less than 100 beatsmin or other
problems such as prematurity may require assistance the differences in
approach to the resuscitation of such babies originate in the physiology
and pathophysiology of acute asphyxia at birth However management
of airway and breathing remain the key features of resuscitation and
where cardiac depression has occurred this is nearly always due to hy-
poxia secondary to respiratory compromise therefore most babies will
respond within 2minus3 min of effective aeration of the lungs and the need
for intubation chest compressions or drugs is rare the international
liaison Committee on Resuscitation (ilCoR) evaluated evidence in 2000
and 2005 in order to provide guidelines for resuscitation they will do
so again for 2010 this evidence is limited in terms of both quantity and
quality and controversies still exist more research is needed to ensure
that our future actions are based upon evidence rather than history this
article will review the recommended approach to resuscitation as well as
some newer evidence
Keywords guidelines neonatal newborn premature resuscitation
Background
In the UK 669 601 babies were born alive in 2006 and most made the transition to extrauterine life without problems Those babies who did not establish adequate regular normal breathing or who had a heart rate of less than 100 beatsmin may have required assistance1 Factual evidence concerning the true requirement for resuscitation at birth is sparse Up to 10 of newborns may require some assistance to begin breathing with less than 1 needing extensive resuscitation2 However just because a baby received resuscitation does not necessarily mean that it was required and rates of intervention may be altered by educa-tion34 or the personnel present at deliveries5 In a UK tertiary centre with a standard approach to resuscitation at birth up to 12 of all babies received some airway assistance with just over 1 being intubated3 In Sweden only 1 of babies over 2500 g required mask or endotracheal tube ventilation at birth of which most responded to the former4
Jonathan Wyllie MBChB FRCPCH is Consultant Neonatologist at the James
Cook University Hospital Marton Road Middlesbrough TS4 3BW UK
paeDiatRiCS anD CHilD HealtH 184 16
Sometimes it is possible to predict babies who are likely to have respiratory depression at birth and to have appropriate per-sonnel present at delivery Guidelines for attendance at deliveries will vary with institution but even when almost 40 of deliv-eries are attended there may still be a further 15 of babies who require unexpected resuscitation5 a proportion that seems to remain whatever changes are made
The physiology of babies requiring help at birth has been summarized previously167 It allows a logical approach to resus-citation (Figure 1) when evidence is lacking and may prompt further research
Resuscitation at birth
PreparationAt birth resuscitation is more likely in babies with intrapartum evidence of significant fetal compromise those less than 35 weeksrsquo gestation those delivering vaginally by the breech and in multiple births Personnel trained in newborn resuscitation should be available at every delivery1 Someone experienced in tracheal intubation and advanced resuscitation should also be easily available for normal low-risk deliveries in hospital and ideally in attendance for deliveries with an increased likelihood of needing resuscitation In the latter cases the equipment and environment can be prepared beforehand including a discussion with the parents Wash your hands put on gloves and consider what help may be needed
Cord clampingAt birth it has long been known that delay in clamping the cord will lead to less anaemia in babies and reduce subsequent iron deficiency8 However few hospitals have practised this interven-tion due to worries about hypothermia and the need to resusci-tate or stabilize babies In developed countries the advantages seemed to be outweighed by the potential disadvantages A recent randomized controlled study of delayed clamping of the cord in premature babies found that the intervention group had less late-onset sepsis and fewer intraventricular haemorrhages9 This is a low-risk strategy which needs further evaluation in order to introduce it without increasing other risk factors in pre-mature deliveries
Assessment and temperature controlAssessment and temperature control for the newborn baby should occur at all deliveries The assessment indicates the need for resuscitation Babies may vary from 23 to 40+ weeksrsquo ges-tation and in weight from 500 to 5000 g They are born naked and wet and if left cannot cope with an environmental tem-perature of less than 32degC However if the term baby is imme-diately dried put skin-to-skin with the mother and covered the delivery room temperature can be as low as 25ndash28degC Obviously the smaller the baby the greater the surface area to mass ratio and the greater the risk of hypothermia Compromised babies are particularly vulnerable10 and hypothermia will lower oxygen tension11 increase metabolic acidosis12 and inhibit surfactant production13
An effective method of maintaining the temperature of prema-ture babies less than 28 weeksrsquo gestation is wrapping them with plastic before drying and then placing them under a radiant
6 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Dry the babyRemove any wet towels and cover
Start the clock or note the time
Give 5 inflation breathsLook for a response
If no increase in heart rate look for chest movement
Re-check head positionApply Jaw thrust
Repeat inflation breathsLook for a response
If no increase in heart rate look for chest movement
Try alternative airway opening manoeuvresRepeat inflation breaths
Look for a response
If no increase in heart rate look for chest movement
If the heart rate is not detectable or slow (lt60)Start compressions
3 compressions to each breath
Reassess heart rate every 30 secondsConsider venous access and drugs
Assess colour tone breathing and heart rate
Open the airway
If not breathing
If still not breathing
If no response
If still no response
When the chest is moving
If meconium present
Baby breathing wellDo not suction the airway
Baby floppy and not breathing wellConsider inspection and suction before
inflation breaths
Head in neutral position
Inflation breathsUse a well-fitting face mask
connedted to a
pressure-limited gas supply
Each breath 2ndash3 seconds
duration at 30 cm H2O for a
term baby
Get help from a second personto support the airway andor
inspect the oropharynx under
direct vision and consider
suction andor insert an
oropharyngeal airway
Chest compressionsCompvent ratio 31
Rate 120 events per minute
Ensure the chest moves with each ventilation breath
If breathingReassess heart rate and monitor baby
If heart rate is satisfactory but increasingContinue ventilation breaths at about 30 per
minute until baby is breathing adequately
If heart rate is satisfactory but increasingContinue ventilation breaths at about 30 per
minute until baby is breathing adequately
If heart rate is increasingStop compressions
Continue ventilation breaths at about 30 per
minute until baby is breathing adequately
If the chest is not movingRecheck head position and repeat inflation
breaths If competent consider intubation
If the chest is still not movingThe airway is the problem
Figure 1 newborn life support (Courtesy of the Resuscitation Council uK)
heater14 There is a small risk of hyperthermia so the temperature must be monitored carefully
An assessment is made of the babyrsquos colour tone respira-tions and heart rate127 The most important of these is heart rate and a stethoscope is more reliable than cord pulsation15 How-ever saturation monitors may offer a more reliable assessment of both heart rate and colour16 but their interpretation requires a detailed knowledge of normal saturations at birth at differing gestations A baby who is apnoeic and floppy in the absence of neurological disease is unconscious and likely to be in terminal apnoea however this does not change the initial approach other
paeDiatRiCS anD CHilD HealtH 184 167
than the need to summon help early APGAR scores are never calculated to guide resuscitation
Airway
If a baby is in primary apnoea then with an open airway the first gasp will start to aerate the lungs and most babies will be able to lsquoresuscitatersquo themselves as shown in physiological stud-ies on animals Neutral positioning of the babyrsquos head chin lift jaw thrust oropharyngeal airways and endotracheal intubation may all be helpful in certain situations if performed correctly17
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Endotracheal intubationThe placement of an endotracheal tube has long been the gold standard of airway control and this remains true in the unconscious baby if it is correctly sized placed and fixed in a timely manner However experience is directly related to effec-tiveness in endotracheal intubation1819 and the success rate of less experienced clinicians such as a resident (STA1-3) or a fel-low (STA3-5) is lower varying between 33 and 68 Even senior neonatologists often take longer than guidelines recom-mend19 Experienced clinicians may judge correct endotracheal position visually or by an increase in heart rate with the first breaths but detection of exhaled carbon dioxide will give more rapid confirmation in larger babies12171920 and this can be par-ticularly useful for less experienced clinicians or those supervis-ing them However not all systems for the detection of exhaled carbon dioxide work in the smallest premature infants
Laryngeal masksLaryngeal masks may be effective for ventilating term newborn babies but there are few data for small premature infants There have been reports of dislodged laryngeal airways during paedi-atric arrests when chest compressions have been administered Although success of placement at first attempt by paediatri-cians is greater with a laryngeal mask than with an endotra-cheal tube21 the only and small randomized controlled trial in the delivery room favoured endotracheal intubation when per-formed by an anaesthetist22 Based mainly upon case reports the laryngeal mask can be recommended when positioning and mask ventilation and endotracheal intubation have failed to secure the airway but not as yet as a primary method of airway control
MeconiumIn 2000 Wisewell et al23 reported a large randomized controlled trial showing that tracheal intubation and suctioning of meco-nium-stained but vigorous babies at birth did not reduce the incidence or severity of meconium aspiration syndrome More recently another randomized trial has now shown that suction-ing on the perineum similarly offers no benefit24 Neither of these practices is recommended but intubation and suction of meconium from the trachea of non-vigorous babies born through meconium-stained liquor is still recommended
Breathing
In the apnoeic baby the first breaths establish the resting lung volume and aerate the fluid-filled alveoli This mechanical effect aided by surface tension within the alveoli causes the initial fall in pulmonary vascular resistance Experimentally this effect occurs even if the lungs are ventilated with nitrogen but is increased when air is used presumably due to the vasodilator effect of 21 oxygen The mechanical stretching of the lung also triggers the activation of cyclo-oxygenase beginning the production of prostacyclin Bradykinin is produced which has a further direct vasodilator effect and also possibly via prostacyclin Therefore adequate airway control and passive ventilation is vital not only because babies requiring resuscitation at birth have an almost uniformly respiratory aetiology but also in order to promote post-natal adaptation and reverse any maladaptation
paeDiatRiCS anD CHilD HealtH 184 16
In term babies peak ventilatory pressures of 20ndash30 cmH2O may be required but the minimal pressure needed to achieve an improvement in heart rate should be used or if there is no response chest wall movement Longer breaths at lower pressure may be more effective in displacing alveolar fluid and establish-ing the resting lung volume in lungs with sufficient surfactant and may improve initial oxygenation However premature new-borns are obviously physiologically and anatomically less pre-pared for delivery than infants at term Over-inflation has been implicated in histological lung damage in animal models and high tidal volumes appear to be equally damaging whether given before or immediately after administration of surfactant How-ever the same effect is not seen if these excessive tidal volumes are delivered 15 min after administration of surfactant2526 It is now thought that both excess end expiratory volume and inad-equate end-expiratory volume may cause lung damage2728 In premature infants it would therefore seem sensible to use lower pressures of 20ndash25 cmH2O12 delivered in a controlled way to prevent over-inflation and to apply positive end-expiratory pres-sure (PEEP) to prevent damage from under-inflation PEEP also improves both lung compliance and gas exchange2930 Without PEEP the airways collapse during the expiratory phase in animal models of newborn resuscitation
If animal data can be extrapolated it would also seem appro-priate to give surfactant as soon as possible to premature babies in order to ameliorate damage2526
The majority of newborn infants requiring resuscitation will re-establish regular respiration after administration of a few breaths which may be due to Headrsquos paradoxical reflex by which the inflation triggers an inspiratory effort
VentilationOnce the lungs are aerated if the newborn remains apnoeic ventilation should be continued at 30ndash60 breathsmin avoiding hyperventilation and using the minimum pressure possible to maintain a heart rate greater than 100 beatsmin
Face mask the majority of infants who require ventilation receive it via a face mask This may be attached to a bagvalve system with a spring lsquoblow offrsquo system or a lsquoT-piecersquo with a set flow and pressure It is important to realize that the bagvalve system is flow sensitive and that the harder the operator presses the greater the flow and the higher the delivered pressure In fact 60 cmH2O can be achieved with vigorous squeezing of a self-inflating bag Therefore it may be advantageous that most opera-tors are unlikely to be as effective as they suppose in creating a seal with the mask31 This is a skill that requires tuition and prac-tice31 In delivering a set pressure T-piece systems such as the Tom Thumbcopy or Neopuffcopy perform better than any bagminusvalve system but require a gas supply There is no evidence that lung compliance can be assessed using any bag system
Continuous airway pressure case series have suggested that early or delivery room use of continuous positive airway pres-sure (CPAP) in premature babies may reduce chronic lung dis-ease There have been two randomized trials of which one was a pilot study The data from the COIN trial do not show any advan-tage other than a reduction in intubation and surfactant use in the intervention group However an excess of pneumothorax
8 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
was also reported The Vermont Oxford Network and the SUP-PORT trials will provide further data but at present the delivery room use of CPAP cannot be widely recommended and should be limited to those units experienced in its use or taking part in research
Air or oxygen oxygen has been in widespread use for resuscita-tion at birth since the 1930s and even hyperbaric oxygen was seriously supported in the 1960s For many years there have been concerns about tissue damage from oxygen deprivation during and after resuscitation It became evident in the 1950s that unrestricted oxygen therapy could have serious conse-quences for future vision More recently concerns have been raised about potential adverse effects on respiratory physiology cerebral circulation and tissue damage from oxygen free radicals even during resuscitation A meta-analysis of four human studies demonstrated a reduction in mortality and no evidence of harm in infants resuscitated in air versus 100 oxygen3233 However there are several significant methodological concerns with these studies and the results should be interpreted with caution There is insufficient evidence to recommend any specific concentration of oxygen to be used for newborn resuscitation Monitoring the oxygen saturation of babies may be helpful but as yet there are no time-related normal target ranges and healthy term babies may take up to 10 min to achieve preductal oxygen saturation of greater than 95 and up to 60 min to achieve this postductally
There is therefore equipoise which would be open to an appropriate randomized controlled trial In the meantime the evidence only supports use of either 21 or 100 oxygen It is provoking to realize that if air had been in constant use since the 1930s there would be insufficient evidence for use of supple-mental oxygen
Circulation
Early resuscitation (temperature control airway breathing) provides oxygenated blood in the pulmonary arterioles which if returned to the heart causes the rate to increase34 If due to acidosis and hypoxia the circulation is ineffective then chest compressions may be needed They should be commenced when the heart rate remains below 60min despite effective airway and breathing management127 The best technique is using two hands to encircle the chest1 A ratio of three compressions to one breath is internationally accepted127 but has no evidence to support it Research has shown that neither compressions nor drugs will work in this situation without oxygenated blood so effective lung aeration and ventilation is essential A logical approach would be to fill the alveoli with air and to compress the chest until they are empty However training and teamwork require an agreed ratio which has therefore not changed since guidelines were first agreed internationally Success is assessed by an increase in heart rate which should therefore be assessed every 30 s Compressions stop when the spontaneous heart rate is greater than 60 beatsmin
In hypoxic newborn animal models successful resuscitation can restore cardiac output and blood pressure to levels above baseline within 5ndash10 min However it should be noted that there is a decline to 30 lower than basal levels within 2 h and that blood pressure is relatively spared suggesting an even greater
paeDiatRiCS anD CHilD HealtH 184 16
reduction in tissue perfusion This should be considered in the later care of any neonate who was hypoxic at birth
Drugs
Neonatal bradycardia at birth is almost always due to hypoxia plusmn acidosis and therefore drugs are rarely needed Adrenaline (epi-nephrine) is reported as being used in between 1 and 4 babies per 2000 births which is a large variation in practice Reported success is also variable and must be interpreted in light of this variation The use of drugs in extremely premature infants is con-troversial Some data suggested good outcomes for babies below 28 weeksrsquo gestation given adrenaline but these were flawed by high numbers of babies receiving resuscitative drugs some before the airway had been appropriately managed Audit data now suggest a poor outcome such that many clinicians would now council against the use of adrenaline and other drugs to resuscitate extremely premature newborn babies
Adrenaline (epinephrine)In 2003 a Cochrane review of randomized controlled trials involv-ing adrenaline use for resuscitation of neonates was unable to identify a single clinical trial35 Despite the lack of human neo-natal data animal models show the potential of adrenaline in asphyxial cardiac arrest and it is reasonable to use it when ade-quate ventilation and chest compressions have failed to increase the heart rate above 60 beatsmin Use 10ndash30 μgkg intrave-nously and preferably via an umbilical venous line The tracheal route cannot be recommended but if used it is likely that doses within this range will be ineffective and 100 μgkg might be tried However the safety of such doses has not been studied
BicarbonateThe use of bicarbonate has long been controversial but many of the concerns relate to the rapid correction of acidosis in neonates after resuscitation or the routine use of bicarbonate infusion nei-ther of which can be advocated There are no published human neonatal data to support its use although some exist from animal studies Animal data have also shown that the binding of adren-aline to receptors in the myocardium is significantly impaired by lactic acidosis and recent work on human lymphocyte beta-adrenergic receptors supports this view Whether this is also true of the more important alpha receptors is unknown In practice reversing intracardiac acidosis may improve myocardial function and assist in achieving a return of spontaneous circulation 1ndash2 mmolkg of bicarbonate may be given but this remains a contro-versial area
VolumeVolume expansion should only be given when it is suspected that the baby has suffered blood loss or the infant appears to be in shock (pale poor perfusion weak pulse) and has not responded adequately to other resuscitative measures If there is no history suggestive of blood loss shock is most likely to be due to myo-cardial dysfunction in which case fluids should be administered cautiously The most logical replacement fluid would be blood but in its absence isotonic crystalloid rather than albumin is the solution of choice given in 10 mlkg aliquots and observing the response Three randomized trials in neonates have shown
9 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
isotonic crystalloid to be as effective as albumin for the treat-ment of hypotension but none has examined either the relative or actual effectiveness in resuscitation A recent blinded randomized study comparing normal saline albumin or no volume expansion in a normovolaemic asphyxiated neonatal animal model showed that volume expansion was not beneficial and made a number of parameters worse36
NaloxoneNaloxone is not recommended as part of the initial resuscita-tion of newborns with respiratory depression Before it is given supporting ventilation should have restored the heart rate and colour The dose is 100 μgkg intravenously or intramuscularly Tracheal administration cannot be recommended Although administration of naloxone to neonates who have been exposed to maternal opioids during labour is a practice of long-standing it lacks the proper evidence of efficacy
Non-response to resuscitation
There are few more frightening situations professionally than applying the correct interventions in resuscitating or stabilizing a baby and getting no response Each stage must be adequately performed before moving onto the next and this requires regular reassessment When experienced help is needed at a newborn resuscitation it is usually the airway and ventilation that require correction If the heart rate does not increase this usually means that the lungs have not been successfully aerated In some cases however it may mean that the heart cannot respond as the cir-culation is inadequate In this situation the only way to check that the lungs have been successfully aerated is to see the chest move with ventilation or to obtain evidence of ventilation from a detector of exhaled carbon dioxide If you do not see chest movement after another five breaths the most likely cause is an obstructed airway either due to incorrect positioning or because the jaw has not been drawn forwards An oropharyngeal airway can be very helpful at this point especially in the term baby Only very occasionally is the airway blocked by mucus vernix blood or meconium but if the airway is guaranteed and there is no heart rate response or chest movement this should be sought by direct suction of the trachea even in the absence of any meconium staining of liquor Pneumothoraces can occur spontaneously after delivery but are rare at resuscitation carried out with pressure-limited devices Equally rare are diaphragmatic hernias that have not been diagnosed antenatally giving problems at resuscitation
If the chest is moving but the heart rate has not responded to resuscitation consider rare possibilities such as fetal blood loss pneumothorax or heart block (mothers with undiagnosed systemic lupus erythematosis delivered for fetal bradycardia) as possibilities With adequate ventilation there is no evidence of oxygen concentrations less than 100 being responsible for prolonged bradycardia or failure to respond although current practice would support increasing the delivered oxygen concen-tration if resuscitation had been commenced using air
Outcome
The prognosis for the full-term baby subjected to sudden acute asphyxia is usually good provided the episode does not last for
paeDiatRiCS anD CHilD HealtH 184 17
long Most babies resuscitated from primary apnoea have no sequelae secondary to the resuscitation Many babies who start to breathe again regularly within 20 min of the circulation being restored recover completely but it is rare for a baby who is still gasping after 30 min to recover
The prognosis for the preterm baby of less than about 34 weeksrsquo gestation subjected to severe acute anoxia is less predict-able This is because of the risk of secondary intraventricular haemorrhage or periventricular intracerebral haemorrhage andor infarction after even a relatively brief asphyxial episode espe-cially in the period immediately around birth
The effects of chronic hypoxia are also difficult to predict but a reasonably clear idea of the extent of the problem should be obtainable within 36ndash48 h of the original chronic asphyxial insult A mild short-lasting state of hyperexcitability usually car-ries a good prognosis even if there is seizure activity but more severe symptoms can be associated with permanent handicap This is seen especially in infants with encephalopathy requiring ventilation
REFERENCEs
1 Biarent D Bingham R Richmond S et al european Resuscitation
Council guidelines for Resuscitation 2005 Section 6 paediatric life
support Resuscitation 2005 67(suppl 1) S97ndashS133
2 international liaison Committee on Resuscitation part 7 neonatal
resuscitation Resuscitation 2005 67 293ndash303
3 Singh J Santosh S Wyllie J mellon a effects of a course in
neonatal resuscitation - evaluation of an educational intervention
on the standard of neonatal resuscitation Resuscitation 2006 68
385ndash389
4 palme-Kilander C methods of resuscitation in low-apgar-score
newborn infants - a national survey Acta Paediatr 1992 81
739ndash744
5 Kroll l twohey l Daubeney p et al Risk factors at delivery and
the need for skilled resuscitation Eur J Obstet Gynecol Reprod Biol
1994 44 175ndash177
6 Wyllie Jp Resuscitation of the newborn The Foundation Years
2007 3(4) 153ndash157
7 Richmond S ed newborn life Support Resuscitation at Birth
london Resuscitation Council 2006
8 Ceriani Cernadas Jm Carroli g pelligrine l et al the effect of timing
of cord clamping on neonatal venous hematocrit values and clinical
outcome at term a randomized controlled trial Pediatrics 2006
117 e779ndashe786
9 mercer JS Vohr BR mcgrath mm padbury JF Wallach m oh W
Delayed cord clamping in very preterm infants reduces the incidence
of intraventricular hemorrhage and late-onset sepsis a randomized
controlled trial Pediatrics 2006 117 1235ndash1242
10 Dahm lS James lS newborn temperature and calculated heat loss
in the delivery room Pediatrics 1972 49 504ndash513
11 Stephenson J Du J tk o the effect of cooling on blood gas
tensions in newborn infants J Pediatr 1970 76 848ndash852
12 gandy gm adamsons Jr K Cunningham n Silverman Wa James lS
thermal environment and acid-base homeostasis in human infants
during the first few hours of life J Clin Invest 1964 43 751ndash758
13 gluck l Kulovich mV eidelman ai et al Biochemical development
of surface activity in mammalian lung pulmonary lecithin synthesis
0 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
in the human fetus and newborn and etiology of the respiratory
distress syndrome Pediatr Res 1972 6 81ndash99
14 Vohra S Roberts RS Zhang B Janes m Schmidt B Heat loss
prevention (Help) in the delivery room a randomised controlled
trial of polyethylene occlusive skin wrapping in very preterm infants
J Pediatr 2004 145 750ndash753
15 owen CJ Wyllie Jp Determination of heart rate in babies at birth
Resuscitation 2004 60 213ndash217
16 orsquoDonnell Cp Kamlin Co Davis pg Carlin JB morley CJ Clinical
assessment of infant colour at delivery Arch Dis Child Fetal
Neonatal Ed 2007 92 F465ndashF467
17 international liaison Committee on Resuscitation part 13 neonatal
Resuscitation guidelines Circulation 2005 112(suppl 24)
iV188ndashiV195
18 leone ta Rich W Finer nn neonatal intubation Success of
pediatric trainees J Pediatr 2005 146 638ndash641
19 orsquoDonnell Cp Kamlin Co Davis pg morley CJ endotracheal
intubation attempts during neonatal resuscitation success
rates duration and adverse effects Pediatrics 2006 117
e16ndash21
20 Repetto Je Donohue pa-CpK Baker SF Kelly l nogee lm use of
capnography in the delivery room for assessment of endotracheal
tube placement J Perinatol 2001 21 284ndash287
21 gandini D Brimacombe JR neonatal resuscitation with laryngeal
mask airway in normal and low birth weight infants Anesth Analg
1999 89 642ndash643
22 esmail n Saleh m ali a laryngeal mask airway versus endotracheal
intubation for apgar score improvement in neonatal resuscitation
Egypt J Anesthiol 2002 18 115ndash121
23 Wiswell te gannon Cm Jacob J et al Delivery room management
of the apparently vigorous meconium-stained neonate results of
the multicenter international collaborative trial Pediatrics 2000
105 1ndash7
24 Vain ne Szyld eg prudent lm Wisewell te aguilar am Vivas ni
oropharyngeal and nasopharyngeal suctioning of meconium-stained
neonates before delivery of their shoulders multicentre randomised
controlled trial Lancet 2004 364 597ndash602
25 Bjorklund lJ ingimarsson J Curstedt t larsson a Robertson B
Werner o lung recruitment at birth does not improve lung function
in immature lambs receiving surfactant Acta Anaes Scand 2001 45
986ndash993
26 Bjorklund lJ ingimarsson J Curstedt t et al manual ventilation
with a few large breaths at birth compromises the therapeutic effect
of subsequent surfactant replacement in immature lambs Pediatr
Res 1997 42 348ndash355
paeDiatRiCS anD CHilD HealtH 184 17
27 taskar V John J evander e Robertson B Jonson B Surfactant
dysfunction makes lungs vulnerable to repetitive collapse and re-
expansion Am J Respir Crit Care Med 1997 155 313ndash320
28 muscedere Jg mullen JB gan K Slutsky aS tidal ventilation at low
airway pressures can augment lung injury Am J Respir Crit Care Med
1994 149 1327ndash1334
29 nilsson R grossman g Robertson B Bronchiolar epithelial lesions
induced in the premature rabbit neonate by short periods of artificial
ventilation Acta Pathol Microbiol Scand 1980 88 359ndash367
30 probyn me Hooper SB Dargaville pa et al positive end expiratory
pressure during resuscitation of premature lambs rapidly improves
blood gases without adversely affecting arterial pressure Pediatr
Res 2004 56 198ndash204
31 Wood Fe morley CJ Dawson Ja et al improved techniques
reduce face mask leak during simulated neonatal resuscitation
study 2 Arch Dis Child Fetal Neonatal Ed in press doi101136
adc2007117788
32 tan a Schulz a orsquoDonnell CpF Davis pg air versus oxygen for
resuscitation of infants at birth Cochrane Database Syst Rev 2004
(3) CD002273
33 Davis pg tan a orsquoDonnell Cp Schulze a Resuscitation of newborn
infants with 100 oxygen or air a systematic review and meta-
analysis Lancet 2004 364 1329ndash1333
34 Dawes g Fetal and neonatal physiology Chicago year Book
publisher 1968 p 141ndash159
35 Ziino aJa Davies mW Davis pg epinephrine for the resuscitation
of apparently stillborn or extremely bradycardic newborn infants
Cochrane Database Syst Rev 2003 (2) CD003849
36 Wyckoff m garcia D margraf l perlman J laptook a Randomized
trial of volume infusion during resuscitation of asphyxiated neonatal
piglets Pediatr Res 2007 61 415ndash420
Practice points
bull Resuscitation at birth is different from that at all other times
of life
bull a standard approach can be applied to most newborn
resuscitation
bull guidelines are based on a rigorous evaluation of evidence
where possible
bull evidence is sparse but evolving
bull most preterm babies require stabilization rather than
resuscitation
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Acidndashbase physiology and blood gas interpretation in the neonateSusern tan
morag Campbell
Abstractacidndashbase balance describes the complex processes that work to main-
tain a stable extracellular pH for optimal cellular function the process
of balancing the production and neutralization of tissue acid provides a
great challenge for newborn infants who have significantly higher rates
of acid production than adults Factors which help maintain a stable
acidndashbase balance include buffers the respiratory system and renal sys-
tem Both intracellular and extracellular buffers resist changes in pH
the most important extracellular buffer system for maintaining stable
pH is the bicarbonate system in response to acidosis or alkalosis the
respiratory system balances the production of acid with the clearance
of Co2 by altering respiratory rate the kidneys provide a delayed but
sustained response to pH imbalance by excreting either acidic or alkaline
urine in response to systemic acidosis and alkalosis respectively in sick
premature infants these systems have a limited capacity completely to
control pH this review discusses the physiology of the three systems
which control acidndashbase balance patterns of clinical abnormalities in
acidndashbase status and their underlying causes are discussed We present
a systematic approach to blood gas analysis and interpretation in new-
born infants
Keywords acidosis alkalosis bicarbonate bloodndashgas analysis
metabolic pH
Introduction
Blood gas analysis is a routine procedure performed on newborn babies receiving respiratory support in the neonatal intensive care The combination of invasive and non-invasive assessment of ventilation and oxygenation enables clinicians appropriately to modify respiratory care according to each individual babyrsquos rapidly changing clinical status
Understanding the fundamentals of acidndashbase balance helps us to use blood gas analysis not only to assess respiratory sta-tus but also to provide information on metabolic status and the adequacy of tissue perfusion
Susern Tan MBBS MRCP is Clinical Fellow at the Neonatal Intensive Care
Unit 6th Floor North Wing St Thomasrsquo Hospital London SE1 7EH UK
Morag Campbell MBChB MRCP is Consultant Neonatologist at the
Neonatal Intensive Care Unit 6th Floor North Wing St Thomasrsquo
Hospital London SE1 7EH UK
paeDiatRiCS anD CHilD HealtH 184 17
What is understood by acid-base balance
Acidndashbase balance refers to the complex physiological processes used by the body to maintain a stable extracellular pH1 A serum pH within the range of 735ndash745 provides the ideal environment for cellular metabolism Maintaining a stable pH is critical as the metabolic activity of proteins is pH dependent and small changes in hydrogen ion (H+) concentration can potentially alter physio-logical function
Acids are substances that yield free H+ in solution while a base accepts H+ and in solution combines with an acid to neu-tralize it In the normal metabolic state H+ are continuously pro-duced and neutralized to maintain a steady pH balance12 The rate of H+ production is two to three times higher in neonates because of their rapid growth rates and increased acid production from protein turnover and bone mineralization The challenge of maintaining a stable pH through processing and neutralizing H+ is therefore greatest in newborn infants
Using exact values of H+ concentration to assess acidndashbase status is cumbersome and it is more commonly expressed as pH defined by the equation
pH = minuslog H+
Maintaining acidndashbase balance
The balance between production and excretion of acids in the body is controlled by buffer systems which have an immediate effect and by the respiratory and the renal systems
Buffer systemsBuffer solutions resist change in pH when acid or alkali is added due to their capacity to absorb or give up H+ The three main buffer systems in the body are the bicarbonate phosphate and protein systems1ndash3 The protein and phosphate buffer systems are intracellular and act as lsquosinksrsquo for extracellular H+ which are exchanged with intracellular potassium (K+) and sodium ions (Na+) In an acute metabolic acidosis hyperkalaemia may develop due to this H+ exchange4
The bicarbonate buffer system is extracellular and consists of a mixture of carbonic acid (H2CO3) and sodium bicarbon-ate (NaHCO3) This buffer system helps maintain a stable pH by soaking up excess H+ with HCO3
minus which in solution forms carbonic acid (H2CO3) Carbonic acid is a weak acid and readily dissociates to give CO2 which is transported in dissolved form to the lungs for excretion
H+ + HCO3minus harr H2CO3 harr H2O + CO2
The bicarbonate system therefore completes the neutraliza-tion of excess H+ and a stable plasma pH is maintained The relationships between pH HCO3
minus and CO2 in this system are described by the HendersonndashHasselbalch equation15
pH = 61 + log HCO3minus003 times CO2
where 61 is the log of the dissociation coefficient of carbonic acid and 003 the solubility of CO2 in plasma Buffers are most potent when there are equal amounts of H+ and HCO3
minus in solution The
2 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
bicarbonate system is not a potent buffer however as HCO3minus
and CO2 are readily altered by the body this system plays a very powerful role in pH homeostasis15
Respiratory regulationThe respiratory system adapts within minutes to hours as part of the acute response to acidosis This system modifies pH by balancing production of H+ with ventilatory clearance of CO2
H+ directly stimulates chemoreceptors in the respiratory cen-tre of the brainstem producing an increase in respiratory rate26 The response to respiratory acidosis is very rapid as CO2 easily diffuses across the bloodndashbrain barrier however in metabolic acidosis compensation is delayed until plasma bicarbonate fully equilibrates with cerebrospinal fluid (CSF) bicarbonate There is an inverse relationship between alveolar ventilation and partial pressure of dissolved carbon dioxide (PaCO2) a reduction in alveolar ventilation raises PaCO2 and decreases pH Changes in pH therefore affect alveolar ventilation and conversely changes in alveolar ventilation cause significant changes in pH
Renal regulationThe kidneys provide a delayed but sustained response to acidndashbase imbalances by excreting either acidic or alkaline urine In full-term and preterm babies the capacity for acid excretion and bicarbonate reabsorption is reduced as glomerular filtration rates are low and tubular function immature7 Renal function matures with gestation postnatal age and glucocorticoid and thyroid hormones78 Due to their limited capacity to preserve HCO3
minus newborn infants have lower serum bicarbonate levels and are predisposed to acidosis7
Bicarbonate is not effectively reabsorbed due to its size and electrical charge Instead intraluminal HCO3
minus combines with secreted H+ in tubular luminal fluid to produce carbonic acid which dissociates to give H2O and CO2 This CO2 diffuses into tubular cells combines with intracellular H2O and forms carbonic acid which liberates HCO3
minus and H+ HCO3minus is then
recovered to the circulation by exchange for chloride ions (Clminus) through the basal cell membrane247
Renal acid secretion occurs at all sites except the loop of Henle Primary active transport accounts for 5 and secondary for the remaining 95 of total H+ excretion Secondary trans-port involves an exchange between luminal Na+ and intracel-lular H+ Both ions bind to a membrane transport protein The Na+ concentration gradient between the tubular lumen and cells enables Na+ drag into the cell which generates energy to fuel active H+ excretion into the tubular lumen1ndash47
Quantifying acidosis
Standard base excess is a calculated value derived from PaCO2 and pH It is expressed as the mmollitre of base above or below normal buffer bases required to correct the pH to 74 at a PaCO2 of 40 mmHg A negative base excess or base deficit indicates an acidosis while a positive base excess indicates a relative alkalosis15
Anion gap is the measured difference between anions and cations in the blood
Anion gap = (Na+ + k+) minus (HCO3+Clminus)
paeDiatRiCS anD CHilD HealtH 184 17
Calculation of the anion gap enables clinicians better to define the underlying cause of a metabolic acidosis9 The common causes of an increased anion gap acidosis in neonates include lactic acidosis due to tissue hypoperfusion and hypoxia it may also be seen with certain inborn errors of metabolism and in uraemia910 The anion gap can help distinguish between the rela-tively benign non-anion gap hyperchloraemic acidosis seen in premature infants and a pathological lactic acidosis due to poor end-organ perfusion1011
Strong ion theory
Stewart described a complex acidndashbase model which proposed that H+ concentration results from the dissociation of water which is influenced by PaCO2 the strong ion difference and plasma weak acids12
Strong ions are ions that dissociate at normal body pH and include Na+ K+ and Clminus Weak acids in plasma which contrib-ute include albumin inorganic phosphate and plasma proteins their concentrations do not change with pH and are therefore a constant The effect of these factors and other unmeasured tissue ions on acidndashbase status can be quantified by the calculation of the strong ion gap (SIG)112 In the neonatal unit it is perhaps more important that we consider how principles of this model may relate to acidndashbase status rather than fully to quantify the SIG Theoretically low albumin and phosphate levels which fre-quently occur in premature infants by reducing the concentra-tion of weak acids can produce a relative alkalosis while high phosphate levels in renal failure may contribute to acidosis
Tissue oxygenation
Oxygenation is closely linked to acidndashbase status as optimal cel-lular function requires oxygen to fuel aerobic metabolism and produce energy In hypoxic conditions anaerobic metabolism predominates which is energy inefficient and results in a lactic acidosis1011
Tissue oxygen availability is related to regional blood flow haemoglobin level and haemoglobin oxygen affinity Arterial blood gases measure the partial pressure of dissolved oxygen (PaO2) which represents a small component of total oxygen con-tent the majority being transported bound to haemoglobin The relationship between percentage haemoglobin saturation (SaO2) and PaO2 is described by the sigmoidal oxyhaemoglobin disso-ciation curve which enables us to relate the two measures to each other235 The affinity of haemoglobin for oxygen is altered by local tissue factors Increases in temperature H+ PaCO2 and 23-diphosphoglycerate (DPG) levels shift the oxyhaemoglobin dissociation curve to the right reducing affinity for oxygen Decreases in temperature H+ PaCO2 and 23-DPG levels shift the curve to the left increasing oxygen affinity1ndash35 In the body haemoglobin oxygen affinity continuously changes increasing in the lungs to enable efficient oxygen uptake and decreasing at tissue level to provide efficient oxygen delivery to metabolically active tissues
Avoiding both hypoxia and hyperoxia is important in the neo-natal unit as deleterious effects of hypoxia are seen in infants with pulmonary hypertension1314 while hyperoxia is associated with an increased incidence of retinopathy of prematurity1516
3 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Clinical acidndashbase imbalances
Clinical acidndashbase imbalances can be respiratory metabolic or a mixture of both These abnormalities may be corrected by the acidndashbase regulatory mechanisms in the body in an attempt to maintain normal pH (Figure 1)
Respiratory acidosisThis occurs when any disorder leads to decreased alveolar ventilation Common causes of respiratory acidosis are listed in Table 1 Reduced respiratory clearance of CO2 means more dissolved CO2 accumulates in the plasma leading to increased production of carbonic acid and H+ Through chemoreceptor stimulation respiratory acidosis rapidly alters ventilation in an attempt to reduce CO226 Chemoreceptor mediated ventila-tory increases may only partly adjust in premature infants with underlying lung disease In babies with a sustained respiratory acidosis eg in chronic lung disease then metabolic compen-sation occurs through increased renal excretion of H+ and reabsorption of HCO3
minus slowly restoring pH to around 80 of normal47
paeDiatRiCS anD CHilD HealtH 184 17
The management of PaCO2 levels in infants receiving mechan-ical ventilation has important clinical implications Premature babies have impaired cerebral autoregulation17 and adverse neurological sequelae are reported in association with high PaCO2 levels18ndash20 Ventilation strategies which advocate lsquoper-missive hypercarbiarsquo have been developed to minimize airways damage from mechanical ventilation21 Published data suggest pulmonary benefits however the safe level of PaCO2 remains to be defined in premature infants2021
Respiratory alkalosisThis occurs when more CO2 is excreted than is produced by the body Pathological conditions leading to respiratory alkalosis are rare Hyperventilation in the neonatal setting is often iatrogenic or may be due to disorders in brainstem control of breathing including hypoxicndashischaemic encephalopathy or primary central nervous system abnormalities (see Table 1)
If respiratory alkalosis is sustained it may be compensated for by reduced reabsorption of filtered bicarbonate Reported adverse associations of low PaCO2 include periventricular leuco-malacia and intraventricular haemorrhage1922
K+
H+
Overventilation
CO2 + H2O harr H2CO3 harr H+ + HCO3ndash
Bicarbonate Buffer
Intracellular Buffer
uarr H+ excretionuarr HCO3
ndash absorption
uarr buffered H+
(NH4+ H2PO4
ndash)uarr ventilation rate
RespiratoryAcidosis
MetabolicAcidosis
darr CO2and uarr pH
RespiratoryAlkalosis
MetabolicAlkalosis
darr H+ anduarr pH
darr ventilation rate
uarrCO2
and darr pH
darr H+ excretiondarr HCO3
ndash absorption
uarrH+ and
darr pH
Brain
Brain
Intracellular Buffer
H+
K+
Sepsis
HypoxiaRDS
Metabolismand growth
Diuretics
Airwayobstruction
Neuromuscularproblems
IEM
Gastric losses
+ +
ndash -
Renal BufferRespiratory Buffer
Figure 1 mechanisms for regulation of extracellular pH iem inborn errors of metabolism RDS respiratory distress syndrome
4 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Common causes of acidndashbase imbalances
pH PCO2 H2CO3 Base excess Common neonatal causes
Respiratory acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
uarr normal normal bull upper airway obstruction choanal atresia
pierre-Robin sequence
bull lung abnormalities respiratory distress
syndrome transient tachypneoa of
newborn pneumonia meconium aspiration
syndrome pulmonary hypoplasia
congenital pulmonary malformations
bull Central hypoventilation hypoxic-ischaemic
encephalopathy intracranial haemorrhage
bull neuromuscular insufficiency congenital
myopathies congenital neuropathies
bull iatrogenic inadequate ventilatory settings
Compensated lower limit
of normal
uarr uarr gt+3
metabolic acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
normal darr ltminus3 increased anion gap
bull lactic acidosis sepsis hypoperfusion
shock necrotizing enterocolitis
bull inorganic acidosis inborn errors of
metabolism renal failure
normal anion gap
bull increased gastrointestinal H2Co3 losses
ileostomy diarrhoea
bull Renal tubular acidoses
Compensated lower limit
of normal
darr darr ltminus3
Respiratory alkalosis Uncompensated gt 745 darr normal normal bull iatrogenic excessive ventilatory settings
bull Compensatory hyperventilation hypoxic-
ischaemic encephalopathy
Compensated higher limit
of normal
darr darr ltminus3
metabolic alkalosis Uncompensated gt 745 normal uarr gt+3 bull gastric losses vomiting non-replacement
of excessive nasogastric aspirates
bull thiazide and loop diuretics
bull Hypokalaemia
Compensated higher limit
of normal
uarr uarr gt+3
Table 1
Metabolic acidosisThis frequently affects infants in the neonatal unit and has many causes1011 (see Table 1) There may be overproduction of tissue acid impaired acid clearance gastrointestinal loss of bicarbonate or an exogenous increased acid load eg chloride total paren-teral nutrition (TPN) or albumin1ndash323
Calculation of the anion gap to distinguish an increased anion gap acidosis from a non-anion gap acidosis is important both for treatment and prognosis1011 Acidosis stimulates respiratory compensation but this is limited in unstable infants Similarly renal compensation with improved HCO3
minus conservation is con-strained by tubular immaturity Treatment of the acidosis should be directed at the underlying cause eg hypoxia hypotension or excess Clminus rather than by administration of base
Metabolic alkalosisThis is unusual in neonates and is most frequently seen in infants with chronic lung disease or heart failure who are receiving diuretics Diuretics cause alkalosis by increasing renal fluid and Na+ losses An active process to reabsorb Na+ occurs in tubule cells which through enhanced H+ secretion and HCO3
minus reab-sorption produce alkalosis27
paeDiatRiCS anD CHilD HealtH 184 17
Metabolic alkalosis may also occur with excessive loss of gas-tric contents eg protracted vomiting or inadequate replacement of nasogastric aspirates (see Table 1)
Interpreting blood gases
Blood gas measurements can provide important diagnostic and prognostic information and a systematic approach to blood gas analysis is described in Table 2 The clinical management of infants with abnormal gases requires a good understanding of acidndashbase physiology and tissue oxygenation and an apprecia-tion of factors which may affect the reliability of samples
Arterial blood sampling is the gold standard however indwelling arterial catheters and arterial stab samples are usually restricted to infants who are critically ill or those who require sig-nificant ongoing intervention Gases are most frequently measured in capillary or venous samples which correlate well with arterial samples for PaCO2 pH and base excess in babies and children receiving intensive care These correlations however are not valid in infants with peripheral vasoconstriction and hypotension2324
Non-invasive monitoring techniques may enable us to reduce the frequency of blood gas sampling Transcutaneous monitoring
5 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
A systematic approach to blood gas analysis
1 Collect the relevant information
bull type of gas ndash capillary or arterial
bull Current respiratory support ndash document level
bull transcutaneous Co2 and Sao2 levels
bull Clarify no significant clinical events before sampling
2 pH accept a range between 730 and 745 in newborn
babies this is lower than in older children is there an
alkalosis (pH gt 745) or an acidosis (lt 730)
3 Co2 aim for a range between 45 and 65 kpa a paCo2 level
more than 65 kpa suggests inadequate alveolar ventilation
while less than 45 kpa suggests hyperventilation Correlate
values with non-invasive measures
4 o2 Can only be assessed from arterial gases aim for pao2
between 60 and 80 kpa Correlate results with pulse
oximetry levels
5 HCo3 and base excess normal HCo3 level is between 20 and
24 mmollitre and bases excess +3 to minus3
6 anion gap look at the anion gap and lactate to help identify
the cause of an acidosis normal lactate levels should be less
than 2 mmollitre
7 Respiratory or metabolic compensation look at the pH and
assess whether it is appropriate for the Co2 level or is there
evidence of compensation
8 interpret use both the clinical history and blood gas
findings to help you identify the primary problem aim your
management at treating the underlying cause
9 Reassess if clinical management changes have been made
repeat the blood gas after an appropriate time interval to
ensure improvement
Table 2
provides a highly accurate and reliable method for measuring PaCO2 through the skin it can however be technically difficult may cause tissue damage and is of limited reliability when peripheral perfusion is reduced25 Continuous end-tidal CO2 measurements correlate well with arterial CO2 values in patients with normal ventilation and perfusion however in babies with lung disease alveolar collapse small tidal volumes and rapid respiratory rates can make these measurements unreliable26 Despite its limitations transcutaneous monitoring provides the best method for CO2 trend monitoring in the neonatal intensive care unit (NICU)25
Oxygen saturation levels can be continuously measured non-invasively using pulse oximetry While oximetry is easy to perform and accurate on occasion SaO2 levels obtained may be unreliable when tissue perfusion is poor or with movement artefact SaO2 monitoring is highly sensitive at detecting hypoxia but is limited in detecting hyperoxia as at levels more than 90 small changes in SaO2 may result in unacceptably large increases in PaO227 It is therefore essential that SaO2 alarm limits are set for all neonates receiving respiratory support to detect hypoxia and prevent hyperoxia1627
Continuous non-invasive monitoring provides invaluable information when managing complex infants in the NICU but it does not replace the need for regular blood gas analysis
paeDiatRiCS anD CHilD HealtH 184 17
ReFeRenCeS
1 Kellum Ja Determinants of blood pH in health and disease
Crit Care 2000 4 6ndash14
2 Quigley R Baum m neonatal acid base balance and disturbances
Semin Perinatol 2004 28 97ndash102
3 Brouillette Rt Waxman DH evaluation of the newbornrsquos blood gas
status Clin Chem 1997 43 215ndash221
4 Chan JC acid-base disorders and the kidney Adv Pediatr 1983 30
401ndash471
5 Siggaard-andersen o the pH-log pCo2 blood acidndashbase nomogram
revised Scand J Lab Invest 1962 14 598ndash604
6 Saetta m mortola Jp interaction of hypoxic and hypercapnic stimuli
on breathing pattern in the newborn rat J Appl Physiol 1987 62
506ndash512
7 Baum m Quigley R postnatal renal development in Seldin DW
giebisch g eds the kidney physiology and pathophysiology new
york lippincott Williams and Wilkins 2000 p 703ndash726
8 ortiz la Quan a Weinberg a et al effect of prenatal
dexamethasone on rat renal development Kidney Int 2001 59
1663ndash1669
9 gabow pa Kaehny WD Fennessey pV goodman Si gross pa
Schrier RW Diagnostic importance of an increased serum anion gap
N Engl J Med 1980 303 854ndash858
10 lorenz Jm Kleinman li markarian K oliver m Fernandez J Serum
anion gap in the differential diagnosis of metabolic acidosis in
critically ill newborns J Pediatr 1999 135 751ndash755
11 Deshpande Sa platt mp association between blood lactate and
acid-base status and mortality in ventilated babies Arch Dis Child
1997 76 F15ndash20
12 Stewart pa modern quantitative acid-base chemistry Can J Physiol
Pharmacol 1983 61 1444ndash1461
13 Dakshinamurti S pathophysiologic mechanisms of persistent
pulmonary hypertension of the newborn Pediatr Pulmonol 2005
39 492ndash503
14 mourani pm ivy DD gao D abman SH pulmonary vascular
effects of inhaled nitric oxide and oxygen tension in
bronchopulmonary dysplasia Am J Respir Crit Care Med 2004
170 1006ndash1013
15 Deulofeut R Critz a adams-Chapman i Sola a avoiding hyperoxia
in infants le 1250 g is associated with improved short- and long-
term outcomes J Perinatol 2006 26 700ndash705
16 Chow lC Wright KW Sola a Can changes in clinical practice
decrease the incidence of severe retinopathy of prematurity in very
low birth weight infants Pediatrics 2003 111 339ndash345
17 Boylan gB young K panerai RB Rennie Jm evans DH Dynamic
cerebral autoregulation in sick newborn infants Pediatr Res 2000
48 12ndash17
18 Kaiser JR gauss CH pont mm Williams DK Hypercapnia during
the first 3 days of life is associated with severe intraventricular
hemorrhage in very low birth weight infants J Perinatol 2006 26
279ndash285
19 Fabres J Carlo Wa phillips V Howard g ambalavanan n Both
extremes of arterial carbon dioxide pressure and the magnitude of
fluctuations in arterial carbon dioxide pressure are associated with
severe intraventricular hemorrhage in preterm infants Pediatrics
2007 119 299ndash305
20 thome uH Carroll W Wu tJ et al outcome of extremely preterm
infants randomized at birth to different paCo2 targets during the
first seven days of life Biol Neonate 2006 90 218ndash225
6 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
21 Carlo Wa Stark aR Wright ll et al minimal ventilation to prevent
bronchopulmonary dysplasia in extremely-low-birth-weight infants
J Pediatr 2002 141 370ndash374
22 okumura a Hayakawa F Kato t et al Hypocarbia in preterm
infants with periventricular leukomalacia the relation between
hypocarbia and mechanical ventilation Pediatrics 2001 107
469ndash475
23 peters o Ryan S matthew l Cheng K lunn J Randomised
controlled trial of acetate in preterm neonates receiving parenteral
nutrition Arch Dis Child 1997 77 F12ndash15
24 yildizda D yapiciolu H yilmaz Hl Sertdemir y Correlation of
simultaneously obtained capillary venous and arterial blood gases
of patients in a paediatric intensive care unit Arch Dis Child 2004
89 176ndash180
25 aliwalas ll noble l nesbitt K et al agreement of carbon
dioxide levels measured by arterial transcutaneous and end tidal
methods in preterm infants 28 weeks gestation J Perinatol 2005
25 26ndash29
26 Hagerty JJ Kleinman me Zurakowski D et al accuracy of a new
low-flow sidestream capnography technology in newborns a pilot
study J Perinatol 2002 22 219ndash225
paeDiatRiCS anD CHilD HealtH 184 17
27 poets CF Wilken m Seidenberg J Southall Dp von der Hardt H
Reliability of a pulse oximeter in the detection of hyperoxemia
J Pediatr 1993 122 87ndash90
Practice points
bull a stable extracellular pH is important for optimal cellular
functioning
bull abnormalities in acidndashbase balance are regulated by buffer
systems and the respiratory and renal tract
bull maintaining a stable pH is challenging for newborn babies
due to their high rates of acid production and immature
regulatory mechanisms
bull arterial or capillary blood gases provide an effective way to
monitor acidndashbase balance in newborns
bull Blood gases should be analysed in a structured manner
assessing pH and then respiratory and metabolic components
bull the treatment of acidndashbase abnormalities should be directed
at the underlying problem not merely at correcting pH
7 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Recognition and management of neonatal seizuresmalcolm levene
AbstractSeizures are the most common major manifestation of central nervous
system dysfunction in the newborn there are many causes but perina-
tal asphyxia and haemorrhagicinfarction lesions account for about 75
there is now considerable evidence that frequent but short seizures in
the neonate affect subsequent neurodevelopmental outcome Studies
using eeg or modified continuous tracing of eeg activity (aeeg or CFm)
have shown that there is often electroconvulsive dissociation this re-
fers to poor correlation between electrical seizures and clinical seizures
Commonly used anticonvulsants appear to increase electroconvulsive
dissociation effective management of neonatal seizures has proved very
disappointing and less than 50 of seizures are abolished by first-line
anticonvulsant medication (phenobarbitone or phenytoin) Drugs such
as midazolam and lidocaine may further reduce seizures but require
more evaluation the challenge is to assess new and more effective anti-
convulsants which are themselves associated with little neurotoxicity
Keywords antiepileptic drugs eeg neonatal seizures neurodegeneration
Convulsions are the most common major neurological sign seen in newborn infants and their incidence estimated from large population studies is 26 per 1000 live births1 Premature infants are over four times more likely to have convulsions than full-term infants12 Neonatal status epilepticus (continuous seizure activity lasting 30 min or more) diagnosed clinically is rare and accounts for only 5 of infants with seizures1 although this is now recognized more frequently as the result of continuous EEG monitoring3
Neonatal convulsions are described as presenting in a num-ber of different ways and various seizure types can be seen in the same baby over a number of hours The frequencies of the various patterns of seizure activity are given in Table 1 In very premature babies and to a lesser extent in term infants minor movement abnormalities may be difficult to identify as subtle seizures These include lip smacking tongue thrusting mouth-ing pedalling type movements of the lower limbs or swimming movements of the arms Apnoea can be a common manifesta-tion of subtle seizures The signs can be protean and vary from baby to baby or even in the same baby Virtually any stereotypic
Malcolm Levene MD FMedSc FRCPCH FRCH is Professor and Head of
Department of Paediatrics and Child Health at University of Leeds Leeds
and Honorary Neonatologist at Leeds General Infirmary Leeds UK
paeDiatRiCS anD CHilD HealtH 184 178
movement may be a manifestation of a seizure disorder in the newborn
Aetiology
The more carefully the fitting baby is investigated the more likely it is that a cause for the seizures will be found A number of recent papers have described the aetiology of neonatal con-vulsions after extensive investigations14 Tekgul et al4 recently studied a consecutive group of full-term infants with evidence of neonatal convulsions (recognized both clinically and on EEG) and reported their outcome Table 2 summarizes these data as well as risk of moderate or severe disability for each causative factor Perinatal asphyxia is the commonest cause for convul-sions in term infants with haemorrhagic or ischaemic lesions also being common
Overall the prognosis for the group of term babies with con-vulsions was good 72 had a favourable outcome Where asphyxia (hypoxicndashischaemic insult) is the cause of neonatal convulsions the outcome is poor in 50 The prognosis for neonatal convulsions when they were due to arterial or cere-brovenous infarction or intracranial haemorrhage was generally good Individually inborn errors are a very rare cause of neo-natal convulsions but in view of the treatable nature of some of these it is essential that these be considered and investigated appropriately5
Patterns of seizure activity in the newborn
Movement pattern Frequency ()
Clonic 50
tonic 20
Subtle 10ndash35 depending on maturity
myoclonic 5
Table 1
Cause incidence and outcome of neonatal convulsions in term infants14
Aetiological factor Incidence () Poor outcome ()
asphyxia 38ndash40 50
Cerebral arteriovenous
infarction
20 0
intracranial haemorrhage 12ndash20 13
Congenital cerebral anomaly 5ndash10 100
Hypoglycaemiahypocalcaemia 3ndash19
infection 3ndash20
inborn error of metabolism 1
unknown cause 10ndash13 0
Refers to moderate and severe neurodevelopmental abnormalitynumbers too small to make meaningful predictions
Table 2
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Controversies in the clinical management of neonatal seizures
In recent years we have learnt much more about the neurobi-ology of seizures and their effect on the developing brain The neonatal brain is in a neurophysiologically hyperexcitable state compared to the more mature brain and therefore is more prone to seizure activity This is due largely to a relative excess of GABA neuroreceptors GABA receptors are usually inhibitory but in the immature brain they have a paradoxically excitatory effect This changes at about term in primates and with progressive develop-ment they adopt a neuroinhibitory role6
The propensity to seizures in the neonatal brain makes resolv-ing the balance of risks between continuing seizure activity on the one hand against potentially adverse effects of therapy on the other a very important equation Added to this is the problem of accurately diagnosing neonatal seizures and whether commonly used anticonvulsants are successful in controlling them
These conundrums can be posed as a series of challenging questions which are discussed below
Do neonatal convulsions cause brain injuryConvulsions are a sign of neurological compromise and may indi-cate significant underlying structural brain damage or biochemi-cal disturbance which may cause further brain damage in its own right There has been considerable debate about the scale of the disability that convulsions cause the immature brain over and above that due to the underlying cause Most of our knowledge comes from studies in rodents and these have provided some tentative answers to this question
Seizures in the mature brain lead to neuronal necrosis but studies in very young rat pups whose brain development is somewhat similar to full-term infants have shown that a series of five brief seizures on five successive days does not cause struc-tural neuronal damage but does produce morphological changes in hippocampal neurones and worryingly deficits in the rat learning and visual spatial memory function in adolescent and adult life7 A single prolonged neonatal convulsion in similarly immature rats does not produce any functional effects8 Others have shown that following priming of the neonatal rat brain by short seizures as described above a further insult comprising induction of status epilepticus in the same rats at an older age causes neuronal necrosis9 This has been referred to as the lsquotwo hit hypothesisrsquo10
A more specific question is does seizure activity in an already significantly compromised brain cause additional neuropathol-ogy Wirrell et al11 studied a series of immature rat pups with the induction of an hypoxicndashischaemic (asphyxial) insult fol-lowed by either chemically-induced fits or a control sham pro-cedure In the more severely asphyxiated animals the degree of brain damage was increased significantly in those that had the additional burden of induced seizures
In summary these studies show that the immature brain is more resistant to short frequent post-seizure damage than the mature brain but despite resulting in no loss of neuronal numbers the function of the brain is permanently affected in later life In the asphyxiated brain seizures appear to have an additional adverse effect on brain damage Furthermore the immature brain that has been lsquoprimedrsquo by early seizures is more
paeDiatRiCS anD CHilD HealtH 184 179
vulnerable to status epilepticus later in life It would appear from these data that frequent seizures in the human infant should be stopped and this begs the question as to whether currently used anticonvulsants effectively control neonatal seizures
Can we rely on clinical versus EEG diagnosis of neonatal convulsionsTraditionally the diagnosis of neonatal convulsions has been made by observation and description of the frequency of abnor-mal movements EEG has been technically difficult in the hostile electrical activity of a neonatal intensive care environment and considerable expertise is required for analysis of the trace It is usually not practical to undertake traditional EEG recordings at the time the baby shows abnormal movements More recently various technological developments have allowed more direct investigation of neuronal electrical activity by either video-EEG or compressed recording of the amplitude integrated EEG (aEEG or CFM)
Rennie et al3 at Kingrsquos College Hospital London have under-taken extensive evaluation of video-EEG and have found that this technique detects many convulsions not recognized by a single channel aEEG or CFM trace Of 19 infants with evidence of convulsions on EEG only four were recognized on CFM but this may have been due to the observersrsquo lack of experi-ence with this technique In other centres that have developed appropriate expertise aEEG or CFM has proved more sensitive to the detection of seizures Video-EEG studies have also shown that many movements interpreted by experienced clinicians to be seizures are not associated with abnormal cortical activity Conversely many electrical seizures are not associated with abnormal movements This is referred to as electroconvulsive dissociation
In summary clinical observation alone to detect the fitting baby is unreliable in that it may either over-detect seizure activ-ity which is not present on EEG or under-detect clinical seizures in infants with EEG-proven convulsions The decision as to which babies to treat with antiepileptic drugs therefore becomes somewhat arbitrary
Do anticonvulsants stop neonatal seizuresAlthough neonatal seizures are common there are few random-ized controlled trials assessing the benefits of antiepileptic drugs (AEDs) in the treatment of this condition Phenobarbitone is the most widely used first-line AED and in an Australasian study 95 of neonatologists and paediatric neurologists used this drug as first-line management12 The most commonly used loading dosage is 20 mgkg but regimens of up to 40 mgkg have been recommended (Table 3)13 Four trials have evaluated the effect of phenobarbitone in abolishing neonatal seizures Two of these studies used EEG to monitor response to the drug1415 and one compared phenobarbitone with phenytoin15 In the latter study seizures were completely controlled in only 43 of babies and in the group where phenytoin was the first drug used com-plete seizure control was achieved in 45 This study switched babies from their first AED to the other if complete control was not obtained on EEG monitoring after exposure to first-line therapy In babies who had been given phenobarbitone as first-line therapy seizure control was only achieved in 57 after phenytoin was added In those given phenytoin first complete
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Dosage regimens for first- second- and third-line anticonvulsants in the neonatal period
Loading dose Second loading dose if first
unsuccessfulMaintenance dose
phenobarbitone 20 mgkg by slow iv injection 10 mgkg iv 25ndash5 mgkg od
phenytoin 20 mgkg iv over 20 min not recommended
midazolam 150ndash200 μgkg iv infusion 1 μgkgmin iv infusion increasing to 5 μgkgmin
until favourable response
lidocaine 2 mgkg iv over 10 min 6 mgkgh for 6 h iv then 4 mgkgh for 12 h then
2 mgkgh for 12 h
lorazepam 005ndash01 mgkg by slow iv injection
Diazepam 03ndash04 mgkg iv over 3ndash5 min
lidocaine should not be used if the infant has previously been treated with phenytoin
Table 3
seizure control was achieved with the adding of phenobarbitone in 62
Boylan et al14 assessed the efficacy of phenobarbitone (20ndash40 mgkg iv over 20 min) in 14 babies monitored by video-EEG in only four was there complete abolition of seizures and in the other 10 electroconvulsive seizure activity increased whereas clinical evidence of seizures reduced This has been termed elec-troclinical dissociation and anticonvulsant drug use in the new-born appears to increase this feature They also showed that the babies least likely to respond to the first-line AED are those with the most abnormal background EEG
Two studies have evaluated the use of phenobarbitone in babies who had sustained significant asphyxial insult at birth Hall et al13 compared high-dose phenobarbitone (mean 39 mgkg) versus standard dose (27 mgkg) and reported fewer convul-sions and a significant reduction of severe disability or death in the high dose group (RR 030 CI 010ndash093) A recent study from India16 of babies with hypoxicndashischaemic encephalopathy ran-domized 25 babies to phenobarbitone (20 mgkg loading dose) and compared them with 20 control babies Only 2 of 25 (4) in the phenobarbitone group developed convulsions compared with 8 of 20 (40) in the control group (p = 001) Because of the specific enrolment criteria (asphyxial insult) neither of these studies is strictly comparable to the studies by Painter et al15 and Boylan et al14 whose intention was to assess the efficacy of first-line anticonvulsant therapy on convulsions of any cause diagnosed either clinically or by EEG
Other anticonvulsants used as second- and third-line drugs have been subject to few studies in the newborn Midazolam is administered as a bolus followed by continuous infusion A recent study17 has shown that in 10 of 13 neonates given intravenous midazolam for status epilepticus control of electri-cal seizures was achieved within the first hour of treatment having been previously shown to be refractory to phenobarbi-tone treatment Some of these babies required a second bolus infusion of midazolam to obtain control of all electrographic seizures
In some parts of Europe lidocaine is used as a third-line anti-convulsant Malingre et al18 evaluated 20 infants refractory to
paeDiatRiCS anD CHilD HealtH 184 180
both phenobarbitone and midazolam and who were then given lidocaine by continuous infusion Lidocaine was effective in abolishing electroconvulsive seizures diagnosed by aEEG in 76 of the treatment courses studied No babies developed cardiac arrhythmias a previously reported complication of lidocaine in older patients As a result of pharmacokinetic studies the dosage regimen has been modified (see Table 3)
In summary phenobarbitone is effective in seizure control in less than 50 of babies and even when combined with phe-nytoin the efficacy of these drugs together remains poor More worrying is the observation that phenobarbitone tends to reduce clinically evident seizures thereby giving the clinician a false sense of security whilst having little or no effect on the num-bers of electroconvulsive disorders This has been summarized appropriately as lsquoafter all these years we still love what doesnrsquot workrsquo19 Both midazolam and lidocaine infusions appear to be effective in abolishing severe seizures in some infants resistant to phenobarbitone Lidocaine should not be given to babies previ-ously exposed to phenytoin for fear of a synergistic adverse effect on cardiac rhythm
Do antiepileptic drugs cause brain damageA riskndashbenefit analysis is needed to evaluate the efficacy of anticonvulsants in stopping neonatal seizures which is poor with standard anticonvulsants as discussed above against the risk of administering the anticonvulsant drugs themselves Phenobarbitone has been reported to have adverse effects on the developing brain including inhibition of brain growth20 neuronal toxicity21 and adverse behavioural and cognitive effects into adult life when administered to young animals22 Phenytoin shows unpredictable plasma levels and potential cardiotoxicity
Recent studies have shown an effect of AED exposure on the developing brain by causing neurodegeneration23 Phenytoin administration to immature rat pups at doses which produce serum levels similar to those achieved in human neonates was associated with widespread neuronal death as a result of apop-tosis (programmed cell death) Phenobarbitone had a similar effect when a dosage regimen similar to 40 mgkg was used and
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
this effect was maximal in the more immature brain Diazepam and clonazepam also resulted in a similar effect Midazolam and lidocaine were not tested in this study The combination of phenobarbitone or phenytoin with diazepam had a particularly profound effect on neurodegeneration
In summary recent data suggest that the commonly used AEDs for neonatal convulsions may in themselves cause neuro-degeneration due to apoptosis with lasting effects on develop-ment Many babies with neonatal convulsions are treated with at least two AEDs and this may produce more severe adverse effects than the seizures themselves
Practical management of neonatal seizures
Assimilation of these data and formulation of a rational policy is difficult when faced with a fitting neonate on an intensive care unit and pressure on the medical staff to lsquodo somethingrsquo but it is important to accept that sometimes doing nothing is preferable to using potentially dangerous drugs in a situation which does not warrant such intervention Many babies who have normal interseizure neurological clinical findings and whose seizures are relatively brief and infrequent probably do not need anticon-vulsant medication A normal or near-normal background EEG trace should reassure the clinician that anticonvulsants can be withheld
Some causes of neonatal convulsions are treatable such as meningitis hypoglycaemia hypocalcaemia and inborn errors of metabolism and each baby should be rapidly and carefully investigated for cause of the convulsions
In some babies clinical assessment of seizures is difficult ie when the baby is very sick small or paralyzed Sometimes it may be difficult to assess the significance of certain movement pat-terns Under these circumstances an EEG may prove to be very helpful In many units EEG is not available out of hours and a simple aEEG or CFM is strongly advised Modern instruments are very simple to apply and prolonged or frequent seizures should be identified with only moderate training The printout can be faxed to a more senior doctor if there is doubt as to what is shown on the trace
The balance of knowledge now is that frequent seizures cause additional damage to the developing brain and that treatment to abolish the seizures is warranted Unfortunately there is little evidence that the majority of seizures can be effectively termi-nated by current standard therapy Furthermore it appears that the more abnormal the background EEG the more difficult it is to control the seizures Nevertheless a written protocol for the management of neonatal convulsions is required on each unit Phenobarbitone and phenytoin remain the mainstay of treat-ment although their effectiveness is disappointing There is little to suggest that midazolam is more effective than lidocaine as third-line therapy but lidocaine is precluded if phenytoin has been previously used
In view of the anxiety as to the neurodegenerative effects on the immature brain of most anticonvulsants used in the neonatal period (particularly when multiple drugs are used) it is prefer-able to use only one drug to maximum dosage before introduc-ing a second In addition the duration of anticonvulsants should be minimized and the drugs stopped at the earliest opportu-nity It is my practice to stop anticonvulsants prior to discharge
paeDiatRiCS anD CHilD HealtH 184 18
from hospital if the baby is neurologically normal on clinical examination
REFEREnCES
1 Ronen gm penney S andrews W the epidemiology of clinical
neonatal seizures in newfoundland a population-based study
J Pediatr 1999 134 71ndash75
2 lanska mJ lanska DJ Baumann RJ et al a population-based study
of neonatal seizures in Fayette County Kentucky Neurology 1995
45 724ndash732
3 Rennie Jm Chorley g Boylan gB et al non-expert use of the
cerebral function monitor for neonatal seizure detection Arch Dis
Child Fetal Neonatal Ed 2004 89 F37ndashF40
4 tekgul H gauvreau K Soul J et al the current etoliologic profile
and neurodevelopmental outcome of seizures in term newborn
infants Pediatrics 2006 117 1270ndash1280
5 Surtees R Wolf n treatable neonatal epilepsy Arch Dis Child 2007
92 659ndash661
6 Ben-ari y Holmes gl effects of seizures on developmental
processes in the immature brain Lancet Neurol 2006 5 1055ndash
1063
7 Holmes gl gairsa Jl Chevassus-au-louis n et al Consequences of
neonatal seizures in the rat morphological and behavioral effects
Ann Neurol 1998 44 845ndash857
8 Stafstrom Ce Chronopoulos a thurber S et al age-dependent
cognitive and behavioural deficits following kainic-acid inducing
seizures Epilepsia 1993 34 420ndash432
9 Schmid R tandon p Stafstrom Ce et al effects of neonatal seizures
on subsequent seizure-induced brain injury Neurology 1999 53
1754ndash1761
10 Hoffmann aF Zhao Q Holmes gl Cognitive impairment following
status epilepticus and recurrent seizures during early development
support for the ldquotwo-hit hypothesisrdquo Epilepsy Behav 2004 5
873ndash877
11 Wirrell eC armstrong ea osman lD et al prolonged seizures
exacerbate perinatal hypoxic-ischemic brain damage Pediatr Res
2001 50 445ndash454
12 Carmo KB Barr p Drug treatment of neonatal seizures by
neonatologists and paediatric neurologists J Paediatr Child Health
2005 41 313ndash316
13 Hall Rt Hall FK Daily DK High-dose phenobarbital therapy in term
newborn infants with severe perinatal asphyxia a randomized
prospective study with three-year follow-up J Pediatr 1998 132
345ndash348
14 Boylan gB Rennie Jm pressler Rm et al phenobarbitone neonatal
seizures and video-eeg Arch Dis Child Fetal Neonatal Ed 2002 86
F165ndash170
15 painter mJ Scher mS Stein aD et al phenobarbital compared with
phenytoin for the treatment of neonatal seizures N Engl J Med
1999 341 485ndash489
16 Singh D Kumar p narang a a randomized controlled trial of
phenobarbital in neonates with hypoxic ischemic encephalopathy
J Matern Fetal Neonatal Med 2005 18 391ndash395
17 Castro Conde JR Borges H Domenech martinez e et al midazolam
in neonatal seizures with no response to phenobarbital Neurology
2005 64 876ndash879
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
18 malingre mm Van Rooij lgm Rademaker Cma et al Development
of an optimal lidocaine infusion strategy for neonatal seizures Eur
J Pediatr 2006 165 598ndash604
19 Sankar R painter mJ neonatal seizures after all these years we still
love what doesnrsquot work Neurology 2005 64 776ndash777
20 Diaz J Schain J Bailey Bg phenobarbital-induced brain growth
retardation in artificially reared rat pups Biol Neonate 1977 32 77ndash82
21 mattson RH phenobarbital toxicity in levy RH Dreifuss Fe
mattson RH et al eds antiepipeptic Drugs 3rd edn new york
Raven 1985 p 341ndash355
22 mikati ma Holmes gl Chronopoulos a et al phenobarbital
modifies seizure-related brain injury in the developing brain Ann
Neurol 1994 36 425ndash453
23 Bittigau p Sifringer m genz K et al antiepileptic drugs and
apoptotic neurodegeneration in the developing brain Proc Natl
Acad Sci U S A 2002 99 15089ndash15094
paeDiatRiCS anD CHilD HealtH 184 182
Practice points
bull the clinician needs to be aware that almost any repetitive
stereotype movement pattern can be a manifestation of
neonatal seizures
bull eeg is important in defining neonatal seizures
bull Frequent short-lived seizures have been shown to cause long-
term neurodevelopmental problems
bull Conventional anticonvulsant medication is ineffective in
abolishing neonatal seizures in greater than 50 of cases
bull there is evidence that exposure of the neonatal brain to
multiple anticonvulsants causes neuronal death
bull Future research is needed to evaluate more effective
anticonvulsants for treating this condition
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
Emotional support for families of sick neonatesMarina nicolaou
cristine Glazebrook
AbstractParents of sick neonates experience high levels of stress anxiety and
depression Most interventions with families of sick infants have focused
on fostering the motherndashinfant relationship through the provision of
information about infant developmental needs or through increased
motherndashinfant contact Many of these studies have reported improved
maternal well-being though there are some concerns about the scope
and practicality of large-scale interventions The few studies to have
prioritized emotional support for parents of sick neonates have pro-
duced encouraging results even interventions requiring relatively few re-
sources such as telephone support parent-to-parent support and group
support have been associated with reduced psychological morbidity for
parents The needs of parents can change throughout their infantrsquos hos-
pitalization and not all want or benefit from the provision of additional
support Thus neonatal intensive care units should aim to provide a
varied flexible and sustainable programme of support options Further
research should focus on the needs of fathers
Keywords mental health neonatal intensive care parents
The admission of an infant to neonatal care is acknowledged to be a source of considerable distress for families This review aims to explore evidence for the psychological impact on families of having an infant in neonatal intensive care and to identify evi-dence for the effectiveness of interventions to promote parental well-being It will conclude with recommendations for strategies to support parents of vulnerable infants and suggestions for fur-ther research
Psychological impact of neonatal care for parents
The majority of research examining the effect on parents of having a sick neonate has focused on families of premature or low birthweight infants Such research has found that parents with a sick neonate exhibit high levels of stress compared to normative samples and to parents of healthy full-term infants1 Singer et al2 examined the stress experienced by mothers of high-risk very low birthweight (VLBW) low-risk VLBW and term
Marina Nicolaou MPhil is a Teaching Assistant at the School of
Community Health Sciences University of Nottingham Nottingham UK
Cristine Glazebrook PhD is a Professor of Health Psychology at the School
of Community Health Sciences University of Nottingham Nottingham UK
PaeDiaTrics anD cHilD HealTH 184 196
infants Several self-report measures were used including the Brief Symptom Inventory the Parenting Stress Index (PSI) the Impact on Family Scale and the Family Inventory of Life Events and Changes (FILE) Mothers of VLBW infants had more psycho-logical distress at 1 month compared to mothers of term infants Mothers of high-risk VLBW infants also reported high psycho-logical distress at 2 years and high levels of parenting stress at 3 years Mothers have also been found to have higher stress levels compared to fathers Shaw et al3 examined the prevalence of acute stress disorder (ASD) in 40 parents whose infants were in the neonatal intensive care unit (NICU) Nearly half of the moth-ers (44) met the criteria for ASD although none of the fathers did Furthermore the severity of the symptoms (measured by the number of concurrent symptoms) was greater for the moth-ers than for the fathers3 The reasons behind this difference have been widely speculated with some believing that it is due to the mothersrsquo greater psychological involvement with the infant as evidenced by their general greater vulnerability to postpartum psychological disorder It could also reflect gender differences in coping style
Having an infant who requires intensive medical care repre-sents a significant emotional burden for families Not only is there extreme anxiety surrounding the infantrsquos health and distress for the childrsquos suffering there is also the unfamiliar and intimidating environment of the NICU to adjust to Hopper in her review of the literature identified sources of stress for parents of sick neo-nates as falling into three areas4 Situational factors included the severity of the infantrsquos illness and how parents adapted to the life crisis of having a sick infant Personal factors involved parental emotions about their roles and the instrumental and informa-tional support which were available to them The third area was classified as environmental sources of stress and included the environment of the NICU and the relationship between parents and members of staff This relationship has been examined by several studies in the nursing literature nurses are seen as ide-ally placed to provide the necessary support and information to parents with sick neonates However whilst some studies have shown that supportive and helpful hospital staff can have a posi-tive effect on parents other studies have highlighted the prob-lems and difficulties which can manifest It has been shown that parents and nurses often have very different ideas about issues eg the necessary skills and competencies needed in an NICU or the characteristics that make a lsquogood motherrsquo
Research has shown that there may be a relationship between high levels of parental stress and an increased likelihood of depression5 Postpartum depression is a psychiatric illness which appears in 10ndash15 of postpartum women Its reported preva-lence rates however have ranged from less than 10 up to 306 depending on the instruments used the population exam-ined and the timing of the research Several factors have been found to be associated with postpartum depression including poor social support and infant-related stressors6 Evidence indi-cates that postnatal depression may be underreported and this is of concern since the mental and psychological health of the mother can affect her relationship with her infant and thus the infantrsquos cognitive and emotional development5 Depressed moth-ers appear to look touch and talk to their infants less frequently and also appear to show fewer positive and more negative faces7 The vocalizations of mothers suffering with depression have also
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
been found to be less effective at promoting cognitive growth and learning in infants8
If researchers are interested in finding ways of providing sup-port for families of sick neonates then they must listen to what such families perceive their needs to be in order to avoid increas-ing anxiety and distress Furthermore the provision of appropri-ate support be it emotional informational or social will enhance parental coping abilities increase self-esteem and reduce anxiety It should be noted though that the research conducted around these issues has often taken lsquosupport needsrsquo as being synony-mous with lsquoinformation needsrsquo Such studies have examined the type the amount and quality of information that parents receive and perceive themselves as needing but have not explored in equal depth the perceived emotional support needs of families who have a sick infant In addition the needs of parents may change throughout their infantrsquos illness Ward examined the per-ceived needs of 52 parents of infants in an NICU9 Parents rated the needs of their hospitalized infant as most important along with the need to be reassured Interestingly they ranked their support needs as least important This research was conducted during the first week of the infantsrsquo hospitalization however which would explain the preoccupation of the parents with the infantrsquos health These results demonstrate that if researchers want to find ways of providing emotional support to parents of sick neonates they must be prepared not only to listen to parents but also to be flexible enough to satisfy the parentsrsquo changing needs and expectations
Interventions aimed at supporting parents
Most interventions that been evaluated in controlled studies have focused on supporting the motherndashinfant relationship and provid-ing information on infant development Many of these interven-tions have included the aim of improving the parental emotional state and thus psychological outcomes such as stress or anxi-ety have been assessed However few studies appear to include fathers This means that strategies implemented to provide emo-tional support to families of sick neonates are often derived from interventions tailored for mothers even though fathers may have different emotional needs
A wide range of interventions with mothers and infants has been evaluated in the NICU Increasing motherndashinfant contact through kangaroo care has been found to reduce maternal anxiety1011 and educational programmes delivered to fami-lies in the NICU have also been associated with reduced emo-tional difficulties in parents12ndash14 Kaaresen and colleagues implemented an intervention which consisted of eight sessions before discharge and four home visits all by trained nurses The sample included 71 premature infants in the intervention group 69 premature infants in the control group and 74 infants in the full-term control group The randomized controlled trial found that the intervention reduced parenting stress in both mothers and fathers of premature infants compared to controls to a level equivalent to parents in the term control group13 At 6 months corrected age mothers of preterm infants who had not received the intervention had total PSI scores which were 17 points higher than the mothers of infants born at term (an effect size of 057) A similar study evaluated the efficacy of an educationalndashbehavioural programmendashCreating Opportunities for
PaeDiaTrics anD cHilD HealTH 184 19
Parent Empowerment (COPE) ndash through a randomized controlled trial with 260 families of premature infants14 COPE was a four-phase educationalndashbehavioural programme which began as early as 2ndash4 d after mothers had given birth and continued until 1 week after discharge from the NICU The programme consisted of audiotaped and written infant behaviour information along with photographs which focused on common behaviours and characteristics of premature infants It also included various par-ent activities in the form of a four-phase workbook which aimed to assist mothers in the implementation of the experimental infor-mation COPE was found significantly to reduce maternal stress in the NICU as well as maternal anxiety and depressive symptoms after hospitalization In contrast a cluster randomized trial of a parenting intervention delivered to mothers of very premature infants from soon after birth showed no benefits for parenting stress1 The authors hypothesized that the intervention had not been of sufficient intensity particularly in the weeks surrounding discharge Neonatal care presents a significant barrier to parent-ing in the early weeks following a very preterm birth and so inter-ventions which focus on the developmental needs of infants and the parentndashchild relationship should particularly aim to support parents as they take on the parenting role There was also concern that the intervention had failed to reach those most at risk
Since large-scale projects can be costly to implement and may often fail to reach the families in most need it may be wiser to focus on intervention programmes which are more practical and easier to implement within a neonatal care setting Research has shown that even interventions which are based on one-off meet-ings with parents of sick neonates can be effective Jotzo and Poets examined the effect of an intervention programme aimed at reducing the severity of traumatic responses as a result of giv-ing birth prematurely15 Their programme consisted of a one-off intervention meeting along with additional psychological help throughout the hospitalization of the infant The meeting cov-ered a variety of issues including a reconstruction of the events shortly before and after the infantrsquos birth relaxation techniques discussion of coping strategies available resources and social support and support during emotional outbursts The measures used included the Impact of Event Scale (IES) and the Peritrau-matic Dissociative Experience Questionnaire At discharge the mothers who received the intervention were found to have a significantly lower traumatic impact as a result of premature birth Furthermore fewer mothers in the intervention group showed symptoms of clinically significant psychological trauma at discharge compared to mothers in the control group (36 vs 76)15 The lsquoParents Circle Programrsquo is another intervention with a similar structure16 This consisted of a 90 min session for parents with the aim of enhancing the developing relationship between parents and infants and to offer parents support A total of 104 parents (59 mothers and 45 fathers) and 44 members of hospital staff were asked to evaluate the programme and their results were analysed using content analysis Families reported gaining perspective on their situation feeling supported becom-ing aware of cues and optimizing interactions and becoming aware of available resources Parents and staff alike felt that participating in the intervention helped parents overcome the difficulties associated with the early time of their infantrsquos hos-pitalization Additional studies have also found positive results with fairly minimal interventions including discussion groups
7 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
in the NICU music during kangaroo care and pairing mothers of sick neonates with trained mothers who had been through similar experiences
Parent support programmes
Parent support programmes (PSPs) which are based in NICUs can provide parents with the opportunity to talk to parents who have been in similar situations and also to discuss their emo-tions with professionals who can help them cope with their situa-tion111718 The parent-to-parent support programme for mothers of preterm infants evaluated by Preyde and Ardal included edu-cational parental support group meetings and individual par-ent-to-parent support (primarily telephone support)19 Measures used included the Parental Stressor Scale NICU the State and the Trait Anxiety Inventories and the Beck Depression Inven-tory After 4 months of participation mothers in the intervention group reported lower levels of stress state anxiety and depres-sion compared to control group mothers The authors speculated however that the participants who were able to meet face to face with other parents were those who benefited the most Hurst conducted a comprehensive survey of an NICU-based PSP This PSP was provided in a variety of formats including a weekly parent support group hospital visitation and 24-h telephone sup-port20 Of the 477 participants 303 families used the PSP dur-ing a 2-year evaluation period with 78 using only one form of support and 18 using two forms Of a sub-sample of 48 parents asked to complete an evaluation of the PSP 92 stated that they would recommend such a programme to other parents Furthermore the majority of parents felt that it made them feel supported and helped them deal with their emotions20 This is an indication that such programmes can be very successful in sup-porting parents throughout their infantrsquos hospitalization It also shows that it can be beneficial to give parents several options and formats when it comes to such support services It is impor-tant to consider though that both the Hurst and the Preyde and Ardal studies found that some participants did not find the sup-port programmes helpful even reporting that they had caused them increased stress and anxiety Therefore it should not be assumed that support programmes will suit every individual and will provide the required support for all parents1920 NICUs need to be flexible enough to provide parents with a range of forms of support to choose from
The increased understanding of the strains that parents of sick neonates have to deal with has also led to efforts to improve customary practices in NICUs Family-centred care focuses on infants and their needs and attempts to redefine the relationship between parents and caregivers These practices strive to provide parents with support during their infantrsquos illness by focusing on freely sharing information and on the collaboration between parents and hospital staff Family-centred care has been found to be associated with several beneficial outcomes including improved parental satisfaction increased parental comfort staff satisfaction and decreased parental stress18 Research is already examining these practices and questioning how these can be improved further Such research reflects the increasing effort focused on lsquohumanizingrsquo the environment in NICUs in order to make parents feel more comfortable about spending time with their infants
PaeDiaTrics anD cHilD HealTH 184 19
Conclusion
Surprisingly few interventions have prioritized the provision of emotional support for parents of sick neonates or accounted for the changing needs and wishes of parents over the course of their infantrsquos care Large-scale supportive education-based inter-ventions have been shown to be effective in reducing parental distress However the feasibility and sustainability of such pro-grammes should also be considered Programmes which require significant additional resources can be expensive and there are also issues of training and quality control Interventions which require significant input from parents may also place additional burdens on families making them potentially less accessible to those most at risk Arguably the aim should be to explore ways of providing acceptable and effective informational support which could be complemented by emotional support from health professionals and from other parents in the unit Increasingly studies are exploring the use of computers and multimedia as an engaging flexible and cost-effective method of targeting indi-vidual needs and providing support and information Such com-puter-based and interactive multimedia interventions have been found to be successful with a range of patient groups and could therefore be examined as a complementary method of providing informational support to families with sick neonates
REfEREnCEs
1 Glazebrook c Marlow n israel c et al randomised trial of a
parenting intervention during neonatal intensive care Arch Dis Child
Fetal Neonatal Ed 2007 92 F438ndash443
2 singer lT salvator a Guo s collin M lilien l Baley J Maternal
psychological distress and parenting stress after the birth of a very
low-birth-weight infant JAMA 1999 281 799ndash805
3 shaw rJ Deblois T ikuta l Ginzburg K Fleisher B Koopman c
acute stress disorder among parents of infants in the neonatal
intensive care nursery Psychosomatics 2006 47 206ndash212
4 Hopper a sources of stress for parents of a sick neonate a
literature review Pediatr Nurs 2000 30 29ndash32
5 Davis l edwards H Mohay H wollin J The impact of very
premature birth on the psychological health of mothers Early Hum
Dev 2003 73 61ndash70
6 Bernazzani O saucier J-F David H Borgeat F Psychosocial
predictors of depressive symptomatology level in postpartum
women J Affect Disord 1997 46 39ndash49
7 Field T infants of depressed mothers Infant Behav Dev 1995 18
1ndash13
8 Kaplan Ps Bachorowski J-a Zarlengo-strouse P child-directed
speech produced by mothers with symptoms of depression fails
to promote associative learning in 4-month-old infants Child Dev
1999 70 560ndash570
9 ward K Perceived needs of parents of critically ill infants in
a neonatal intensive care unit (nicU) Pediatr Nurs 2001 27
281ndash286
10 lai Hl chen cJ Peng Tc et al randomized controlled trial of music
during kangaroo care on maternal state anxiety and preterm infantsrsquo
responses Int J Nurs Stud 2006 43 139ndash146
8 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
11 Tallandini Ma scalembra c Kangaroo mother care and mother-
premature infant dyadic interaction Infant Ment Health J 2006 27
251ndash275
12 Ohgi s Fukuda M akiyama T Gima H effect of an early intervention
programme on low birthweight infants with cerebral injuries
J Paediatr Child Health 2004 40 689ndash695
13 Kaaresen Pi ronning Ja Ulvund se Dahl lB a randomized
controlled trial of the effectiveness of an early-intervention program
in reducing parenting stress after preterm birth Pediatrics 2006
118 e9ndash19
14 Melnyk BM Feinstein nF alpert-Gillis l et al reducing premature
infantsrsquo length of stay and improving parentsrsquo mental health
outcomes with the creating opportunities for parent empowerment
(cOPe) neonatal intensive care unit program a randomized
controlled trial Pediatrics 2006 118 e1414ndash1427
15 Jotzo M Poets cF Helping parents cope with the trauma of
premature birth an evaluation of a trauma-preventive psychological
intervention Pediatrics 2005 115 915ndash919
16 Pearson J andersen K evaluation of a program to promote positive
parenting in the neonatal intensive care unit Neonatal Netw 2001
20 43ndash48
17 roman l lindsay J Boger r et al Parent-to-parent support
initiated in the neonatal intensive care unit Res Nurs Health 1995
18 385ndash394
18 Meyer ec coll cTG lester BM Boukydis cFZ McDonough sM Oh w
Family-based intervention improves maternal psychological well-
being and feeding interaction of preterm infants Pediatrics 1994
93 241ndash246
PaeDiaTrics anD cHilD HealTH 184 19
19 Preyde M ardal F effectiveness of a parent ldquobuddyrdquo program for
mothers of very preterm infants in a neonatal intensive care unit
CMAJ 2003 168 969ndash973
20 Hurst i One size does not fit all Parentsrsquo evaluations of a support
program in a newborn intensive care nursery J Perinat Neonatal
Nurs 2006 20 252ndash261
Practice points
bull Parents of sick neonates experience significant distress and
exhibit higher levels of stress anxiety and depression than
parents of healthy infants
bull educational support emotional support and increased
motherndashinfant contact have been shown to promote maternal
well-being
bull emotional support for fathers has been largely neglected in
the research literature
bull Parents benefit from a choice of supportive facilities which
could include face-to-face sessions with health professionals
telephone support hospital visitation parent-to-parent
support and unit-based group support meetings
bull Parentsrsquo support needs can change during their infantrsquos
hospitalization and not all parents want or benefit from the
provision of additional information and emotional support in
the neonatal unit
9 copy 2008 elsevier ltd all rights reserved
Personal Practice
When should enteral feeds be started in preterm infantsnicholas D embleton
AbstractPaediatricians are regularly faced with the question of when best to start
enteral feeds in preterm infants this is important as longer term out-
come may be compromised by sub-optimal nutrition in early life clinical
factors that may affect the decision to start and the risk and benefits
are discussed
Keywords breast milk feeding nutrition parenteral nutrition
Key points in the history
Alice is lsquonutritionally vulnerablersquo and whilst this may not be immediately apparent it will affect her long term outcome Her energy stores are extremely limited and consist primarily of pro-tein She has less than 5 fat and little energy associated with stored glycogen She is losing about 1 gkgd protein equivalent so she needs at least that and a minimum of 50ndash60 kcalkg of energy just to maintain the status quo let alone grow
Her weight is on the 25th centile Review of any antenatal his-tory may reveal whether fetal growth was normal Fetal growth retardation can occur with a weight greater than 10th centile The presence of antenatal absent or reversed end diastolic flow in the umbilical artery indicates poor gut blood flow This increases the risk of necrotizing enterocolitis (NEC) and might suggest a more cautious approach to starting feeds1
She has no important cardiovascular problems but if she were hypotensive gut blood flow may be low There is no umbilical
Nicholas D Embleton BSC (Hons) MBBS (Hons) MD FRCPCH is Consultant in
Neonatal Medicine at Newcastle Neonatal Service Royal Victoria
Infirmary Newcastle upon Tyne NE1 4LP UK
Should you start feeds at a day of age
alice was born following spontaneous labour at 30 weeksrsquo
gestation she weighed 1300 g and is now 18 h old she was
briefly ventilated and then extubated to continuous positive
airway pressure 12 h ago in 35 oxygen she has had caffeine
citrate but still has intermittent episodes of self-correcting
apnoea she was commenced on iv 10 dextrose but this was
replaced by a parenteral amino acid solution (referred to as
lsquotPnrsquo) along with intralipid at 0900 this morning serum glucose
is 11 mmoll and blood pressure is 42 systolic
PaeDiatrics anD cHilD HealtH 184 20
arterial catheter in situ but there is no good evidence that this should delay the decision to start feeds Her glucose is high but this is quite common in a baby like this Could this be a sign of sepsis Caffeine does not affect the incidence of NEC2 The great-est risk factor for NEC in this case is prematurity
What else might be found on examination
Up until 24 h ago she was swallowing large amounts of amniotic fluid What will have changed since then
General examination should confirm peripheral perfusion lsquogestaltrsquo view (does she look lsquowellrsquo) and cardiovascular status lsquoBowel soundsrsquo are not usually helpful
The most important variable likely to affect gut perfusion is the arterial duct Precordial lsquoheaversquo and a loud murmur are sug-gestive but it is possible to have a significant ductal shunt in a baby with a normal examination Cardiac ultrasound will con-firm this diagnosis It might be better to treat a large shunt first with indometacin and to delay starting feeds for a further 24 h
It is not possible to assess gut perfusion clinically but normal perfusion elsewhere (adequate urine output usually indicates adequate renal perfusion) would be reassuring Most preterm babies have a few abdominal lsquoloopsrsquo visible but a distended abdomen with many palpable loops suggests ileus This might be secondary to sepsis or poor gut blood flow Preterm babies do not pass much meconium in the first 24ndash48 h
Balance of risks between starting and withholding feeds
Alice requires 35ndash4 gkgd of protein and 120 kcalkgd to grow3 This will initially be provided parenterally Delaying feeds increases the risk of gut villous atrophy and prolongs the need for lsquototal parenteral nutrition (TPN)rsquo TPN requires intravenous access and so increases the risk of sepsis and when prolonged use is required combined with the lack of enteral feeding may result in hepatic impairment
Delaying feeds may allow a gut that has been chronically under-perfused to re-establish more normal perfusion although normal gut endocrine function digestive enzyme upregulation and motility require a source of intraluminal nutrients1 A recent study suggested benefit from delaying the introduction of feeds4 but methodologi-cal problems exist5 Although a Cochrane meta-analysis suggested no benefit only two studies were included6 A large UK-based trial is examining the effect of early or late feeding in preterm infants who were born growth retarded following identification of antena-tal absent or reversed end diastolic flow in the umbilical artery7
When starting feeds what volume should be used
There are no good data to guide this decision We start with 24 mlkg (1 mlkgh) and then increase by this amount each day Most babies achieve full enteral feeds (ge150 mlkgd) by a week of age Feeding guidelines improve the outcome8 Measure-ment or assessment of gastric aspirates is not consistently useful in predicting subsequent feeding intolerance or development of NEC Aspirate volumes equivalent to or sometimes greater than the amount given in the preceding 1ndash2 h are usually normal Most aspirates have a greenish colour Thick bloody or intensely bile-stained aspirates require detailed assessment
0 copy 2008 elsevier ltd all rights reserved
Personal Practice
What else affects decisions and outcome
Feeding success is affected by sepsis and NEC Scrupulous atten-tion should be paid to hand washing and intravenous access and blood sampling should be minimized There is no good evidence to support the routine use of pro-kinetic agents or H2 blockers
The most important clinical intervention affecting the occur-rence of NEC is the use of breast milk9 All efforts should be directed at persuading parents of the benefits and supporting the process Some clinicians delay starting feeds for a further 24 h whilst expressed breast milk becomes available Donor breast milk might be equally efficacious10
RefeRenceS
1 Dorling J Kempley s leaf a Feeding growth restricted preterm
infants with abnormal antenatal Doppler results Arch Dis Child Fetal
Neonatal Ed 2005 90 F359ndash363
2 schmidt B roberts rs Davis P et al caffeine therapy for apnea of
prematurity N Engl J Med 2006 354 2112ndash2121
PaeDiatrics anD cHilD HealtH 184 20
3 embleton nD Pang n cooke rJ Postnatal malnutrition and growth
retardation an inevitable consequence of current recommendations
in preterm infants Pediatrics 2001 107 270ndash273
4 Berseth cl Bisquera Ja Paje VU Prolonging small feeding volumes
early in life decreases the incidence of necrotizing enterocolitis in
very low birth weight infants Pediatrics 2003 111 529ndash534
5 Menon G Boyle eM embleton nD et al introduction of enteral
feeds in preterm infants Pediatrics 2004 114 327ndash328
6 Kennedy Ka tyson Je chamnanvanikij s early versus delayed
initiation of progressive enteral feedings for parenterally fed low
birth weight or preterm infants Cochrane Database Syst Rev 2000
cD001970
7 wwwnpeuoxacukadept
8 Patole sK de Klerk n impact of standardised feeding regimens on
incidence of neonatal necrotising enterocolitis a systematic review
and meta-analysis of observational studies Arch Dis Child Fetal
Neonatal Ed 2005 90 F147ndash151
9 lucas a cole tJ Breast milk and neonatal necrotising enterocolitis
Lancet 1990 336 1519ndash1523
10 Boyd ca Quigley Ma Brocklehurst P Donor breast milk versus
infant formula for preterm infants systematic review and meta-
analysis Arch Dis Child Fetal Neonatal Ed 2007 92 F169ndash175
1 copy 2008 elsevier ltd all rights reserved
self-assessment
Case 1A term male infant born to consanguineous parents is assessed at 24 h of age due to poor feeding profuse yellow watery diar-rhoea and irritability He weighed 32 kg at birth and delivery was uneventful There was no polyhydramnios He has been breastfed since birth On examination he is pale with a non-tender but distended abdomen and reduced bowel sounds His weight is 275 kg and he looks dehydrated Examination is otherwise normal
Initial investigations (normal values in parentheses) showed
sodium 149 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 65 mmollitre (25ndash75)
creatinine 147 μmollitre (40ndash110)
chloride 119 mmollitre (95ndash105)
haemoglobin 172 gdl (140ndash200)
White blood cell count 80 times 109litre (100ndash260)
Platelet count 302 times 109litre (150ndash400)
arterial blood gas
ph 720 (730ndash745)
PcO2 23 kPa (46ndash60)
Bicarbonate 68 mmollitre (220ndash260)
Base excess minus186 mmollitre (minus20 to +20)
lactate 59 mmollitre (06ndash24)
An abdominal X-ray shows distended bowel loops with no intramural thickening or pneumoperitoneum (Figure 1)
He was given nil by mouth and received intravenous fluids and antibiotics His dehydration improved but the metabolic acidosis and diarrhoea persisted despite receiving no enteral feeds and the commencement of total parenteral nutrition Blood and stool cultures were negative
1 Which of the following best describes these results Choose ONE answer ONLY from the followingA Hypernatraemia hyperchloraemic metabolic acidosis
with increased anion gapB Hypernatraemia hyperchloraemic metabolic acidosis
with normal anion gap
Manish Sadarangani BM BCh MA MRCPCH is Clinical Research Fellow
at the Department of Paediatrics University of Oxford Centre for
Clinical Vaccinology and Tropical Medicine Churchill Hospital
Oxford OX3 7LJ UK
Shabna Rajapaksa MB BChir MA MRCPCH is Specialist Registrar in
Paediatrics at the Paediatric Intensive Care Unit John Radcliffe
Hospital Oxford OX3 9DU UK
Nicholas Mann MD FRCP FRCPCH DCH is Consultant Paediatrician at the
Department of Paediatrics Royal Berkshire Hospital Reading RG1
5AN UK
self-assessment
C Hypernatraemic dehydration and compensated metabolic acidosis
D Acute renal failureE Renal tubular acidosis
2 What is the likely diagnosis Choose ONE answer ONLY from the followingA Hirschsprung disease ndash long segmentB Cystic fibrosis with meconium ileusC Microvillus inclusion diseaseD Cowrsquos milk protein intoleranceE Lactose intolerance
3 What is the investigation of choice Choose ONE answer ONLY from the followingA Rectal biopsy with staining for acetylcholine receptorsB Immunoreactive trypsinC Gastrointestinal endoscopy and biopsyD Stool microscopy and cultureE Stool reducing substances
Case 2A 4-year-old boy presents with a 3 d history of jaundice and a florid rash He has had orange urine and there is no change in his stool colour His family originate from Kosovo and have lived in the UK for the last 8 years He has never left the UK There is no history of blood transfusion or sex-ual abuse The grandmother was recently diagnosed with hepatitis B
On examination he is well apyrexial and mildly jaundiced with cervical and axillary lymphadenopathy He has an exten-sive papular rash over the face extremities and trunk (Figure 2) There is 3 cm hepatomegaly with no splenomegaly or ascites Examination is otherwise normal
Figure 1 abdominal X-ray of baby
Paediatrics and child health 184 202 copy 2008 elsevier ltd all rights reserved
self-assessment
Initial investigations are as follows
haemoglobin 110 gdl (113ndash135)
White blood cell count 108 times 109litre (50ndash150)
Platelet count 278 times 109litre (150ndash400)
inr 10 (08ndash12)
aPt ratio 10 (08ndash13)
sodium 140 mmollitre (135ndash145)
Potassium 42 mmollitre (35ndash50)
Urea 56 mmollitre (25ndash75)
creatinine 65 μmollitre (45ndash120)
total bilirubin 66 μmollitre (0ndash15)
conjugated bilirubin 23 μmollitre (0ndash10)
alanine aminotransferase (alt) 2033 iUlitre (0ndash35)
alkaline phosphatase 987 iUlitre (71ndash234)
Gamma-glutamyl transferase (GGt) 870 iUlitre (0ndash51)
1 What is the name of this rash Choose ONE answer ONLY from the followingA Erythema multiformeB Erythema migransC GianottiminusCrosti syndromeD EczemaE Dermatitis herpetiformis
2 What is the most likely diagnosis Choose ONE Answer ONLY from the followingA Autoimmune hepatitisB Hepatitis BC Hepatitis DD Wilson diseaseE Alpha-1 antitrypsin deficiency
3 What is the best means of management Choose ONE answer ONLY from the followingA Isolation until the jaundice disappearsB ImmunosuppressionC Copper chelating agents and genetic counsellingD Patient and family education with consideration of
antiviral agentsE Liver transplantation
Case 3A 10-month-old boy presents with 3 weeks of vomiting and constipation ndash he is passing hard stools every 2ndash3 days He has fallen from the 9th to below the 04th centile in the last 6 weeks He passed meconium within the first 24 h of life On examina-tion he looks pale and there are some dysmorphic features ndash a short nose long philtrum and wide mouth He has normal heart sounds with a grade 3 ejection systolic murmur loudest at the upper right sternal edge Examination is otherwise normal
Initial investigations are as follows
haemoglobin 91 gdl (113ndash141)
total white blood cell count 124 times 109litre (60ndash170)
Platelet count 407 times 109litre (150ndash400)
sodium 144 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 78 mmollitre (25ndash75)
creatinine 78 μmollitre (45ndash120)
albumin 52 glitre (35ndash50)
corrected calcium 384 mmollitre (238ndash263)
Phosphate 167 mmollitre (099ndash157)
1 What is the most likely diagnosis Choose ONE answer ONLY from the followingA HyperparathyroidismB Acute leukaemiaC Williams syndromeD Hypervitaminosis DE Familial hypocalciuric hypercalcaemia
2 Which investigation would be most useful in establishing the diagnosis Choose ONE answer ONLY from the followingA Intact parathyroid hormone assayB Blood filmC Fluorescent in-situ hybridization for 7q1123 deletionD 25-hydroxyvitamin D assayE Urine calciumcreatinine ratio
3 Which of the following treatments would not be suitable for this patient Choose ONE answer ONLY from the followingA Low calcium dietB Normal saline infusionC FurosemideD CorticosteroidsE Bisphosphonates
Case 4A 10-week-old girl presents with a 2-day history of poor feed-ing Her mother has been concerned about weakness since birth She only has a flicker of movement in the arms none in the legs and has a weak cry She has been passing urine and opening her bowels normally She was born at full term by normal delivery and did not require any resuscitation at birth Normal fetal movements were felt antenatally and there was no polyhydramnios She is the first child of non- consanguineous parents and there is no significant family his-tory On examination she is alert and fixing and following appropriately She has a weak cry and a weak suck There is reduced central and peripheral tone with marked head lag
Figure 2 rash found on examination
Paediatrics and child health 184 203 copy 2008 elsevier ltd all rights reserved
self-assessment
Muscle power is grade 3 out of 5 in the arms and legs There is no muscle or tongue fasciculation and she has absent reflexes throughout The remainder of the examination is normal
Electromyogram shows irregular polyphasic motor unit potentials with marked instability consistent with a dener-vating and re-innervating process (Figure 3)
1 Which of the following additional investigations may be helpful Choose ONE answer ONLY from the followingA Nerve conduction studiesB Creatine kinase assayC Muscle biopsyD SMN1 gene analysisE All of the above
2 What is the most likely cause of this childrsquos symptoms Choose ONE answer ONLY from the followingA Congenital myotonic dystrophyB Duchenne muscular dystrophyC PraderminusWilli syndromeD Spinal muscular atrophyE Mitochondrial myopathy
3 What is the mode of inheritance of this disease Choose ONE answer ONLY from the followingA X-linked recessiveB Autosomal recessiveC Autosomal dominantD MitochondrialE Sporadic
Case 5A 13-year-old girl presents with a 3-week history of fever up to 40degC night sweats and headache She has a reduced appetite with some weight loss She has no other specific symptoms She was on holiday in China 7 months ago On examination she looks well and has a temperature of 387degC There is no lymphadenopathy and no rashes Examination is entirely normal
Results of investigations are as follows
haemoglobin 126 gdl (120ndash160)
total white blood cell count 132 times 109litre (43ndash108)
neutrophil count 115 times 109litre (25ndash75)
Platelet count 244 times 109litre (150ndash400)
Blood film neutrophilia with left shift
erythrocyte sedimentation rate 63 mmh (1ndash20)
c-reactive protein 219 mglitre (0ndash5)
Blood culture Streptococcus intermedius
from anaerobic bottle only
csf culture negative
Magnetic resonance imaging (MRI) of the brain shows acute frontal sinusitis with a large intracranial frontal extra-dural empyema (Figure 4)
1 Which of the following would be appropriate management Choose ONE answer ONLY from the followingA A 12-week course of intravenous antibioticsB Drainage of the frontal sinus followed by 2 weeks of
intravenous antibioticsC Drainage of the empyema followed by 2 weeks of
intravenous antibioticsD Drainage of the empyema and the frontal sinus
followed by 2 weeks of oral antibiotics
1151
1152
1153
1154
1155
1156
1157
1158
1159
1200
50ms 1mV
Figure 3 electromyogram recording from the patient Figure 4 Parasagittal section from mri scan of patient
Paediatrics and child health 184 204 copy 2008 elsevier ltd all rights reserved
self-assessment
E Drainage of the empyema and the frontal sinus followed by 8 weeks of intravenous antibiotics
2 Streptococcus intermedius is a potential pathogen in which of the following infections Choose ONE answer ONLY from the followingA Liver abscessB Urinary tract infectionC MeningitisD Thoracic empyemaE Pneumonia
3 Which of the following statements regarding lsquopyrexia of unknown originrsquo in children is false Choose ONE answer ONLY from the followingA Malignancy is the underlying pathology in 5ndash15 of
casesB An aetiology will be found in over 90 of casesC The most common cause is infectionD A rheumatological cause is found in 10ndash20 of casesE Familial Mediterranean fever can occur in children of
non-Mediterranean ethnicity
Answers
Case 11 AThe anion gap is a useful tool to differentiate the causes of a metabolic acidosis It is calculated by the equation
Anion gap = [Na K ] [Cl HCO ]3+ + minus minus+ minus +
It represents the effect of unmeasured anions on the plasma pH and is normally 10ndash18 mmollitre
2 CMicrovillus inclusion disease is a severe autosomal recessive enteropathy that is typically apparent within hours or days after birth It is the second most common cause of protracted diarrhoea in the newborn after infectious causes It is characterized by severe yellow watery diarrhoea and malabsorption due to hypoplasia andor atrophy of the villi of the small intestine secondary to an inherited defect in the brush border membrane This results in severe dehydration malnutrition and metabolic acidosis due to bicarbonate loss from the gut
3 CDiagnosis of microvillus inclusion disease is made on small bowel biopsy Electron microscopy findings are of intracellular brush border inclusions and densely packed apical cytoplasmic vesicular bodies indicating microvillous atrophy There is no cure Treatment is supportive with total parenteral nutrition and consideration of small bowel transplantation
Further reAding
Goulet O ruemmele f causes and management of intestinal failure
in children Gastroenterology 2006 130(suppl 1) s16ndash28
rhoads Jm Vogler rc lacey sr et al microvillus inclusion disease
In vitro jejunal electrolyte transport Gastroenterology 1991
100 811ndash817
Case 21 CGianottindashCrosti syndrome is a distinct self-limiting rash commonly associated with viral infections in children between 2 and 6 years of age It presents as multiple pink to redminusbrown papules or papulovesicles which may be pruritic and can become confluent Gianotti and Crosti initially described the exanthema as associated with hepatitis B virus and they termed it papular acrodermatitis of childhood It can occur in several viral diseases eg hepatitis A B and C coxsackie viruses and cytomegalovirus
2 BHepatitis is a syndrome characterized by inflammation or injury of liver cells which may develop into cell necrosis and subsequently fibrosis andor cirrhosis Biochemically there are raised liver enzymes The degree of transaminase elevation does not correlate with the severity of the disease process Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of viral hepatitis
3 DHepatitis B infection is transmitted via blood sexually or vertically Infection may be acute or chronic Diagnostic markers are the presence of surface antigen (HBsAg) and HBV DNA The presence of e antigen (HBeAg) indicates high infectivity Infected newborns have a 95 risk of becoming carriers this risk decreases with infection acquired later in childhood Approximately 15ndash25 of HBV carriers will die from cirrhosis or hepatocellular carcinoma Extrahepatic findings are more common in older children and include membranous glomerulonephritis and GianottiminusCrosti syndrome Fulminant hepatic failure occurs in severe cases resulting in persistent jaundice encephalopathy and coagulopathy Management includes counselling family members monitoring for ongoing liver disease and consideration of antiviral therapy
Further reAding
Brandt O abeck d Gianotti r Burgdorf W Gianotti crosti
syndrome J Am Acad Dermatol 2006 54 136ndash145
slowik mK Jhaveri r hepatitis B and c viruses in infants and
young children Semin Pediatr Infect Dis 2005 16 296ndash305
Case 31 CHypercalcaemia is uncommon in infancy The most common symptoms in this age group are irritability vomiting and constipation It may be a manifestation of Williams syndrome vitamin D or calcium excess as well as disorders associated with reduced bone formation such as hypophosphatasia or increased bone resorption such as malignancy Occasionally
Paediatrics and child health 184 205 copy 2008 elsevier ltd all rights reserved
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-
SympoSium neonatology
42 Aringgren J Sjoumlrs g Sedin g ambient humidity influences the rate of
skin barrier maturation in extremely preterm infants J Pediatr 2006
148 613ndash617
43 Sinclair l Sinn J Higher versus lower humidity for the prevention of
morbidity and mortality in preterm infants in incubators (protocol)
Cochrane Database Syst Rev 2007 issue 2 art noCD006472
doi10100214651858
44 Hey en Katz g the optimum thermal environment for naked
babies Arch Dis Child 1970 45 328ndash334
45 Sauer pJJ Dane HJ Visser HKa new standards for neutral thermal
environment of healthy very low birthweight infants in week one of
life Arch Dis Child 1984 59 18ndash22
46 Dollberg S Xi y Donnelly mm a noninvasive alternative to rectal
thermometry for continuous measurement of core temperature in
the piglet Pediatr Res 1993 34 512ndash517
47 messaritakis J anagnostakis D laskari H Katerelos C Rectal-skin
temperature difference in septicaemic newborn infants Arch Dis
Child 1990 65 380ndash382
paeDiatRiCS anD CHilD HealtH 184 16
Practice points
bull Hypothermia in the newborn infant is associated with adverse
outcome
bull Despite improvements in technology the preterm baby is still
at high risk of hypothermia immediately after delivery
bull prevention of evaporative heat losses eliminates hypothermia
at resuscitation
bull High evaporative fluid losses must be prevented if the baby
is nursed under a radiant heater
bull more studies are needed to determine the optimum
management after delivery and to show if reducing
transepidermal water loss has an effect on the rate of skin
maturation
bull Continuous monitoring and display of a central and peripheral
temperature gives early warning of developing cold stress
0 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemiaJ m Hawdon
Abstractat birth the newborn baby undergoes many adaptive changes to inde-
pendent extrauterine life these include the changes of metabolic adap-
tation which must be understood in order to identify and manage the
conditions in which metabolic adaptation is delayed impaired or fails
resulting in low levels of glucose and other metabolic fuels which in turn
affect neonatal neurological function and if prolonged and severe cause
potential adverse outcome Babies identified as at risk of impaired met-
abolic adaptation must undergo clinical monitoring including accurate
blood glucose monitoring tailored to their condition Babies who present
with abnormal clinical signs in association with a low blood glucose level
must be investigated for underlying cause and treated promptly preven-
tion and treatment of clinically significant hypoglycaemia must be planned
to avoid compromising successful establishment of breast feeding
Keywords alternative fuels blood glucose breast feeding neonatal
metabolic adaptation operational thresholds risk factors
Introduction
At birth the newborn baby undergoes many adaptive changes to independent extrauterine life These include the changes of met-abolic adaptation essential to ensure energy provision to vital organs and then to sustain growth and further development The changes involved in metabolic adaptation must be understood in order to identify and manage the conditions in which metabolic adaptation is delayed impaired or fails The clinical outcome of these circumstances is usually referred to with the single short-hand diagnostic term lsquoneonatal hypoglycaemiarsquo However as will be illustrated in this article it is not appropriate to ascribe a diagnostic label to neonatal hypoglycaemia first because glucose is not the only fuel in the neonatersquos fuel economy and second because hypoglycaemia is the consequence of a number of vari-ous underlying disorders and thus does not in itself warrant a diagnostic label
There have been extensive studies of metabolic adaptation in human neonates and neonatal non-human mammals The latter studies have identified those mammals most similar to humans
J M Hawdon MA MBBS MRCP FRCPCH PhD is Consultant Neonatologist and
Honorary Senior Lecturer at UCL EGA Institute for Womenrsquos Health
Elizabeth Garrett Anderson and Obstetric Hospital University College
London Hospitals NHS Foundation Trust Huntley Street London UK
paeDiatRiCS anD CHilD HealtH 184 161
in terms of metabolic adaptation and sought to compare nutri-tionally comparable time frames eg suckling versus weaning periods Whilst the processes of metabolic adaptation are well described in term and preterm human neonates there are few if any clinical studies in human neonates of sufficient rigour to provide evidence for the circumstances in which brain injury may occur and thus it is not possible to provide evidence-based guide-lines for the prevention and management of clinically significant hypoglycaemia Therefore recommendations in this article and in the referenced review articles by recognized experts remain pragmatic and urge clinicians to individualize management for each baby placing heavy emphasis on careful clinical evaluation rather than single numerical definitions of brain-injuring hypogly-caemia and on detecting and treating underlying pathologies1ndash6
Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
During intrauterine life the fetus receives via the placenta a con-stant supply of nutrients initially for growth but in the third tri-mester also for storage Glucose crosses the healthy placenta at a rate of approximately 5 mgkgmin In addition to that required for basal fetal metabolism glucose is converted to glycogen which is stored in the liver cardiac muscle and central nervous system In the third trimester excess glucose is converted to tri-glycerides which are stored in adipose tissue
Insulin is an important fetal hormone to ensure glucose and other substrates are utilized for growth and storage but in nor-mal circumstances insulin is not required for fetal glucose con-trol The exception is for the infant of the mother with poorly controlled diabetes when transfer of glucose across the placenta is at a higher rate driven by the maternalndashfetal concentration gra-dient This results in increased insulin secretion excess growth and increased storage of glycogen and adipose tissue (macroso-mia) along with increased risk of intracellular hypoxia
Conversely in the fetus affected by severe placental insuffi-ciency transfer of glucose and other nutrients across the placenta is at a lower rate and the fetus is required to metabolize first its own fuel stores and then structural proteins (eg in muscle) to ensure energy delivery to the vital organs assisted by the redis-tribution of blood flow to these organs Should placental function deteriorate further these adaptive responses fail Fetal hypogly-caemia has been described in these circumstances78
When placental nutrition abruptly ceases at birth the healthy neonate is dependent upon endocrine changes to initiate meta-bolic adaptation Insulin levels fall steadily and the action of any residual circulating insulin is overcome by the surge of the coun-ter-regulatory hormones glucagon and the catecholamines This change in the balance of glucoregulatory hormones induces the activity of key enzymes for glycogenolysis (release of glucose from glycogen stores) gluconeogenesis (production of glucose from precursors including glycerol and amino acids) lipolysis (release of free fatty acids and glycerol from adipose tissue stores) and beta-oxidation of fatty acids to produce ketone bodies910 If fasting is prolonged structural protein is broken down to release gluconeogenic amino acids Other than lipolysis and proteolysis all of these processes take place in the liver Glycogenolysis also takes place in cardiac muscle and the central nervous system providing immediate energy (in the form of glucose or lactate)
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
at this crucial time411 Clearly during this catabolic phase of immediate postnatal nutrition prior to the establishment of suck-ling feeds provision of energy for vital organ function is at the expense of growth and fuel storage
The postnatal metabolic transition is characterized by low cir-culating blood glucose concentrations compared to those of older infants and children often for a number of days12 This is almost always of no pathological significance for a number of reasons including differences in the function and metabolic requirements of the brain and importantly the production and utilization of alter-native fuels lactate and ketone bodies which are in plentiful supply in the neonate341213ndash20 An important finding from clinical studies and of clinical relevance to those caring for mothers and babies is that in all groups of infants studied to date those who are breast fed have higher circulating ketone body levels than those who are formula fed even after correcting for blood glucose levels102122
There are circumstances however when hypoglycaemia is severe and prolonged and conditions when alternative fuel pro-duction is also impaired or fails In these circumstances low blood glucose levels do acquire clinical significance The key metabolic processes and the risk factors for impaired metabolic adaptation are summarized in Table 1
Metabolic changes at birth ndash key hormones and metabolic processes and risk factors for impaired metabolic adaptation
Postnatal metabolic
changes
Risk factors
Hormones
insulin falls neonatal hyperinsulinism ndash infant of
diabetic mother or idiopathic
glucagon surge possibly blunted by iv glucose or
formula feeds
Catecholamine surge maternal beta-blocker medication
(Cortisol ndash weak effect) (pituitary or adrenal insufficiency)
Metabolic processes
glygogenolysis preterm intrauterine growth
restriction (iugR) ndash reduced stores
perinatal hypoxia-ischaemia ndash stores
utilized
Hyperinsulinism
maternal beta-blocker medication
glycogen storage disorders
gluconeogenesis Hyperinsulinism
maternal beta-blocker medication
Hepatic dysfunction
Very rare inborn errors of metabolism
lipolysis preterm iugR ndash reduced stores
Hyperinsulinism
maternal beta-blocker medication
Ketogenesis Defects of beta-oxidation of fatty
acids
Hepatic dysfunction
Table 1
paeDiatRiCS anD CHilD HealtH 184 16
Impaired metabolic adaptation
Risk factors for impaired metabolic adaptation vary and may be related to any of the following reduced body fuel stores failure of the normal endocrine changes at birth systemic illnesses which impede function of the liver where the key metabolic processes occur or rarely inborn errors of metabolism (see Table 1)
It is well recognized that significant hypoglycaemia will result in a reduced level of consciousness andor fits However it is always important to be alert for detect and treat an underlying pathology which could be causing both the hypoglycaemia and the abnormal signs Often abnormal signs and hypoglycaemia are co-morbidities eg a primary neurological problem causes both abnormal neurological signs and hypoglycaemia secondary to poor feeding For this reason all possible underlying causes for presentation with hypoglycaemia must be considered and investigations planned accordingly Investigations for inborn errors of metabolism and endocrine disorders are most informa-tive if carried out when blood glucose levels are low
There have been extensive efforts to use data from clinical stud-ies of the human neonate to determine the significance of neonatal hypoglycaemia in terms of neurophysiological neurodevelopmental and neuroradiological sequelae However there are major difficul-ties in interpreting these clinical studies as to date these have been flawed by confounding factors such as immaturity placental insuf-ficiency and co-existing complications by heterogeneity of subjects and by failure to take into account protective mechanisms11423 The evidence from both animal and human studies suggests lsquopurersquo hypo-glycaemic brain injury is rare and for hypoglycaemic brain injury to occur there must be co-existing failure of metabolic adaptation such that alternative fuels are not available There is no evidence that lsquotransitionalrsquo hypoglycaemia in the healthy neonate is associated with acute or long term sequelae and indeed even for babies in the at-risk groups on many occasions protective factors will prevail
Diagnosis of clinically significant hypoglycaemia
lsquoNeonatal hypoglycaemiarsquo is a commonly cited diagnosis most often based on a single blood glucose level and using inaccurate methods of measurement and with disregard for the presence or absence of associated clinical signs In the many published texts and local guidelines there is no consistency of approach For this reason a multinational group of experts attempted to examine critically the evidence on which clinical recommendations should be made1 Fol-lowing detailed analysis the authors considered it impossible to define hypoglycaemia as a single blood glucose level and instead suggested operational thresholds and therapeutic goals They con-cluded that low blood glucose levels accompanied by neurological signs should be investigated and treated regardless of the blood glu-cose level They also pragmatically concluded that a blood glucose level below 10 mmollitre should be treated immediately In babies who are at risk of impaired metabolic adaptation but who have no clinical signs it is recommended that interventions to raise blood glucose level are considered if blood glucose levels are persistently below 20 mmollitre For sick and very low birthweight babies who are likely to have a requirement for intravenous glucose there should be a lsquotherapeutic goalrsquo to maintain blood glucose levels above 25 mmollitre Where there is known hyperinsulinism (a very high-risk condition characterized by high intravenous glucose
2 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
requirements to maintain normoglycaemia) an operational thresh-old and therapeutic goal of 35 mmollitre has been proposed24
Finally there must be careful consideration of the infant of the diabetic mother In extreme and rare cases there may be signifi-cant but transient hyperinsulinism and in these cases the thera-peutic goal must be 35 mmollitre More commonly babies whose mothersrsquo diabetes has been well controlled will have normal lsquotran-sitional hypoglycaemiarsquo or slightly delayed metabolic adaptation while insulin levels fall postnatally There must be careful and repeated clinical assessment including blood glucose monitoring For infants of diabetic mothers who have no evidence of signifi-cant hyperinsulinism and no abnormal clinical signs there is no evidence that the operational threshold for hyperinsulinism must be applied Indeed to do so would result in separation of large numbers of healthy babies from their mothers with the conse-quent impact upon breast feeding and resource allocation25
The operational thresholds for various groups of babies are summarized in Table 2
The guidance relating to operational thresholds is predicated upon the accurate measurement of blood glucose levels It is now well known that the commonly used reagent strips are insufficiently accurate to diagnose hypoglycaemia and monitor at-risk infants and there must be access to equipment which allows immediate and accurate determination of blood glucose levels1426ndash28
Blood glucose monitoring
An accurate method for blood glucose monitoring must be employed as described above The sample should be free flowing venous or from a warm heel such that the blood flows freely without squeezing
Blood of high haematocrit often yields low blood glucose lev-els because of dilution of glucose by red cell water However this is also clinically relevant because polycythaemia is itself a high-risk situation Therefore in polycythaemic infants both the haematocrit and blood glucose level must be monitored and both acted upon accordingly
Operational thresholds for blood glucose levels in the management of babies at risk of impaired metabolic adaptation124
Clinical condition Blood glucose level at which
to consider intervention and
therapeutic goal
all at-risk babies lt10 mmollitre
abnormal neurological
signs
intervene regardless of blood
glucose levelSystematically unwell baby therapeutic goal of 25 mmollitre
at-risk babies no abnormal
neurological signs
persistently lt20 mmollitre
Hyperinsulinism 35 mmollitre
Table 2
paeDiatRiCS anD CHilD HealtH 184 163
Only babies in at-risk groups or babies who have abnormal neurological signs should be subjected to blood glucose monitor-ing (Table 3)
It is important not to commence blood glucose monitoring too soon after birth as to do so would fail to differentiate the baby with incipient hypoglycaemia from the baby undergoing the nor-mal postnatal fall in blood glucose level It is recommended in the otherwise healthy but at-risk baby to wait until around 3 h after birth to make the first blood glucose estimation2528 In prac-tice this is usually before the second feed assuming best practice of offering a baby a breast (or if necessary formula feed) imme-diately after birth Clearly if the baby is unwell or has abnormal clinical signs in the first 3 h they will be treated according to clinical condition which will include intravenous fluids and the therapeutic goal described above would apply
Similarly the temptation to measure blood glucose level shortly (within 2 h) after intravenous glucose has been discon-tinued must be avoided In this circumstance as at birth blood glucose levels fall and then subsequently rise in response to coun-ter-regulation It is this effective rise which must be assessed by blood glucose measurement at least 2 h after a change is made (provided the baby remains clinically well)
Blood glucose levels rise after a feed and fall to a nadir before the subsequent feed As our concern is the lowest blood glucose level during the feed cycle and as this measurement may assist in determining best feed frequency it is important that pre-feed blood glucose concentration is measured There is no clinical value in measuring a post-feed blood glucose level as this may be falsely reassuring and this practice subjects babies to more frequent heel pricks or venesections than is necessary
Finally consideration must be given to when to discontinue blood glucose monitoring This will depend upon the babyrsquos clin-ical condition feeding pattern and underlying disorder or risk factors for impaired metabolic adaptation
Prevention and management of clinically significant hypoglycaemia
In babies at risk of clinically significant hypoglycaemia and who are well enough to tolerate enteral feeds milk feeds are the
At-risk babies for whom blood glucose monitoring is recommended
abnormal neurological signs
Systemically unwell eg suspected or proven infection
hypoxicndashischaemic encephalopathy
preterm (lt 37 weeks)
intrauterine growth restriction (lt 2nd centile and any baby with
signs of wasting)
infant of diabetic mother
polycythaemia
maternal beta-blocker medication
Suspected hyperinsulinism
Suspected inborn error of metabolism or endocrine disorder
Table 3
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
mainstay of prevention For babies who are able to feed orally breast feeding should be first choice and there must be maximal support for the mother to do so This is a key clinical priority for midwives and paediatricians
If there are concerns regarding adequacy of breast feeding to prevent hypoglycaemia the mother should be encouraged to commence expression of milk from very soon after birth If there is insufficient breast milk to prevent babies reaching the opera-tional thresholds described above there should be judicious use of formula milk using only the smallest amount required to keep the babyrsquos glucose in the required range Formula milk in exces-sive quantities has been demonstrated to suppress normal meta-bolic adaptation2122
In babies for whom early enteral feeds are not appropriate or not tolerated or for whom enteral feeding does not prevent blood glucose level falling below operational thresholds intravenous glucose infusion at rates around 4ndash5 mgkgmin (58ndash72 mlkgd of 10 dextrose) are usually sufficient to prevent hypoglycae-mia If blood glucose levels remain below therapeutic goals the rate of infusion may be steadily increased Excess glucose infu-sion over and above that required to maintain the therapeutic goal will stimulate insulin and there is a risk of rebound hypo-glycaemia if high rate glucose infusions are too rapidly reduced Milk feeds if tolerated should be continued if intravenous glu-cose is commenced
If infused volume of glucose solution becomes excessive in order to maintain therapeutic goals or if fluid restriction must be applied more concentrated glucose concentrations must be infused through a central venous line This is particularly rel-evant to the hyperinsulinaemic baby in whom glucose infusion rates in excess of 8ndash10 mgkgmin are required to maintain ther-apeutic goals There is a high risk of severe and brain-damaging hypoglycaemia if treatment is delayed or fails to raise blood glu-cose levels and management of these babies requires consulta-tion with or referral to a specialist centre24
If there is presentation of hypoglycaemia with abnormal clinical signs or a very low blood glucose level (less than 1 mmollitre) this mandates urgent treatment with intravenous glucose The rates of glucose infusion described above are usually sufficient to bring the blood glucose level rapidly to the therapeutic goal without a bolus of glucose being necessary In fact a bolus dose of glucose will result in a peak blood glucose level and then an insulin surge making subsequent management problematical This is minimized by the use of a lsquomini-bolusrsquo should a bolus of glucose be required ndash 200 mg glucosekg (2 mlkg of 10 dextrose)28 Indications for mini-bolus are infants presenting with fits or coma or an lsquounre-cordablersquo or zero blood glucose level A mini-bolus should always be followed with glucose infusion or an increased glucose infusion rate if a baby already receiving intravenous glucose has required a mini-bolus
The temptation to supplement enteral feeds with glucose polymers and energy supplements (eg Duocal) or to use oral glucose gels or solutions (eg Hypostop) should be avoided as this carries a risk of necrotizing enterocolitis is likely to suppress normal metabolic adaptation and will suppress the appetite of the baby for effective oral feeding
Finally there are additional medications which may be employed in specific circumstances (Table 4) More detailed descriptions are given elsewhere242728 Babies who have hypoglycaemia which
paeDiatRiCS anD CHilD HealtH 184 164
is difficult to control by the measures described above and who require these additional treatments should be cared for in a centre which has expertise in metabolic and endocrinological conditions
Summary
Much controversy and confusion has surrounded neonatal hypo-glycaemia but this usually arises as a result of failure to under-stand the processes of normal metabolic adaptation and the fact that hypoglycaemia is a presenting sign rather than a diagnosis in itself Plans for investigation and management must be based upon the most likely underlying cause of impaired metabolic adaptation and take into account the clinical condition of the baby This is counter to the current trend to propose rigid pro-tocols and algorithms and re-introduces the value of detailed clinical evaluation and decision making The mainstay of man-agement is close clinical observation of vulnerable infants and energy provision tailored to their individual needs whilst avoid-ing excessively invasive management (namely unnecessary sep-aration of mother and baby routine or excessive formula milk supplementation or intravenous glucose administration) which themselves inhibit protective metabolic responses and impede successful establishment of breast feeding
ReFeRenCeS
1 Cornblath m Hawdon Jm Williams aF et al Controversies regarding
definition of neonatal hypoglycemia Suggested operational
thresholds Pediatrics 2000 105 1141ndash1145
2 Cornblath m ichord R Hypoglycemia in the neonate Semin
Perinatol 2000 24 136ndash149
3 Vannucci RC Vannucci SJ Hypoglycaemic brain injury Semin
Neonatol 2001 6 147ndash155
4 Rozance pJ Hay WW Hypoglycaemia in newborn infants features
associated with adverse outcomes Biol Neonate 2006 90 74ndash86
5 Hawdon Jm Hypoglycaemia in newborn infants defining the
features associated with adverse outcomes ndash a challenging remit
Biol Neonate 2006 90 87ndash88
6 Williams aF neonatal hypoglycaemia clinical and legal aspects
Semin Fetal Neonatal Med 2005 10 363ndash368
7 Soothill pW nicolaides KH Campbell S prenatal asphyxia
hyperlacticaemia hypoglycaemia and erythroblastosis in growth
retarded fetuses BMJ 1987 294 1051ndash1053
Additional medication in specific conditions (if these are required there must also be referral to a specialist centre)
Medication Indication
glucagon intramuscular bolus dose of 200 μgkg
transient rise in blood glucose level eg
when difficulty re-siting intravenous infusion
Diazoxide Hyperinsulinism
Hydorcortisone pituitary or adrenal insufficiency
Table 4
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
8 Hawdon Jm Ward platt mp mcphail S Cameron H Walkinshaw Sa
prediction of impaired metabolic adaptation by antenatal Doppler
studies in small for gestational age fetuses Arch Dis Child 1992
67 787ndash792
9 Deshpande S Hawdon Jm et al adaptation to extrauterine life in
Rodeck C Whittle m eds Fetal medicine Basic Science and Clinical
practice edinburgh Churchill livingstone 1999
10 Ward platt m Deshpande S metabolic adaptation at birth Semin
Fetal Neonatal Med 2005 10 341ndash350
11 eyre Ja Stuart ag Forsyth RJ Heaviside D Bartlett K glucose
export from the brain in man evidence for a role for astrocytic
glycogen as a reservoir of glucose for neural metabolism Brain Res
1994 28 349ndash352
12 Hawdon Jm Ward platt mp aynsley-green a patterns of metabolic
adaptation for preterm and term infants in the first neonatal week
Arch Dis Child 1992 67 357ndash365
13 Hawdon Jm Ward platt mp aynsley-green a prevention and
management of neonatal hypoglycaemia Arch Dis Child Fetal
Neonatal Ed 1994 70 F60ndash64
14 Hawdon Jm Hypoglycaemia and the neonatal brain Eur J Paediatr
1999 158 S9ndash12
15 massieu l Haces ml montiel t Hernaacutendez-Fonseca K acetoacetate
protects hippocampal neurons against glutamate-mediated neuronal
damage during glycolysis inhibition Neuroscience 2003 120
365ndash378
16 yamada Ka Rensing n thio ll Ketogenic diet reduces
hypoglycaemia-induced neuronal death in young rats Neurosci Lett
2005 385 210ndash214
17 nehlig a Brain uptake and metabolism of ketone bodies in animal
models Prostaglandins Leukot Essent Fatty Acids 2004 70
265ndash275
18 Hernaacutendez mJ Vannucci RC Salcedo a Brennan RW Cerebral blood
flow and metabolism during hypoglycemia in newborn dogs
J Neurochem 1980 35 622ndash628
19 Vannucci RC nardis ee Vannucci SJ Campbell pa Cerebral
carbohydrate and energy metabolism during hypoglycaemia in
newborn dogs Am J Physiol 1981 256 H1659ndashH1666
20 anwar m Vannucci RC autoradiographic determination of regional
cerebral blood flow during hypoglycaemia in newborn dogs Pediatr
Res 1988 24 41ndash45
21 Hawdon Jm Williams aF et al Formula supplements given to
healthy breastfed preterm babies inhibit postnatal metabolic
adaptation results of a randomised controlled trial Arch Dis Child
2000 82 a30
paeDiatRiCS anD CHilD HealtH 184 16
22 de Rooy l Hawdon Jm nutritional factors that affect the postnatal
metabolic adaptation of full-term small- and large-for gestational
age infants Pediatrics 2002 109 e42
23 Hawdon Jm Hypoglycaemia and brain injury ndash when neonatal
metabolic adaptation fails in levene m ed Fetal and neonatal
neurology and neurosurgery edinburgh Churchill livingstone in
press
24 Hussain K Congenital hyperinsulinism Semin Fetal Neonatal Med
2005 10 369ndash376
25 acolet D Diabetes in pregnancy Caring for the Baby after Birth
CemaCH 2007 2
26 Hussain K Sharief n the inaccuracy of venous and capillary blood
glucose measurement using reagent strips in the newborn period
and the effect of haematocrit Early Hum Dev 2000 57 111ndash121
27 Hawdon Jm Disorders of blood glucose homeostasis in the neonate
in Rennie Jm ed Robertonrsquos textbook of neonatology 4th edn
edinburgh Churchill livingstone 2005
28 Deshpande S Ward platt mp the investigation and management
of neonatal hypoglycaemia Semin Fetal Neonatal Med 2005 10
351ndash361
Practice points
bull identify risk factors for impaired metabolic adaptation
bull Clinical monitoring including accurate blood glucose
measurement for at-risk babies
bull Feed at-risk babies soon after birth and maintain thermal
homeostasis
bull take first blood glucose level at 3ndash4 h of age
bull intervene in at-risk baby with no clinical signs if two
consecutive blood glucose measurements lt 20 mmollitre
bull intervene in any baby with blood glucose measurement
lt 10 mmollitre
bull intervene in any baby with abnormal clinical signs regardless
of blood glucose level
bull investigate for underlying cause of failure of metabolic
adaptation
bull maintain lactation and breast feeding
5 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Resuscitation of the term and premature babyJonathan Wyllie
Abstractalthough most newly born babies establish normal respiration and
circulation without help up to 1minus2 may require some resuscitation
or stabilization Babies who do not establish adequate regular normal
breathing or who have a heart rate of less than 100 beatsmin or other
problems such as prematurity may require assistance the differences in
approach to the resuscitation of such babies originate in the physiology
and pathophysiology of acute asphyxia at birth However management
of airway and breathing remain the key features of resuscitation and
where cardiac depression has occurred this is nearly always due to hy-
poxia secondary to respiratory compromise therefore most babies will
respond within 2minus3 min of effective aeration of the lungs and the need
for intubation chest compressions or drugs is rare the international
liaison Committee on Resuscitation (ilCoR) evaluated evidence in 2000
and 2005 in order to provide guidelines for resuscitation they will do
so again for 2010 this evidence is limited in terms of both quantity and
quality and controversies still exist more research is needed to ensure
that our future actions are based upon evidence rather than history this
article will review the recommended approach to resuscitation as well as
some newer evidence
Keywords guidelines neonatal newborn premature resuscitation
Background
In the UK 669 601 babies were born alive in 2006 and most made the transition to extrauterine life without problems Those babies who did not establish adequate regular normal breathing or who had a heart rate of less than 100 beatsmin may have required assistance1 Factual evidence concerning the true requirement for resuscitation at birth is sparse Up to 10 of newborns may require some assistance to begin breathing with less than 1 needing extensive resuscitation2 However just because a baby received resuscitation does not necessarily mean that it was required and rates of intervention may be altered by educa-tion34 or the personnel present at deliveries5 In a UK tertiary centre with a standard approach to resuscitation at birth up to 12 of all babies received some airway assistance with just over 1 being intubated3 In Sweden only 1 of babies over 2500 g required mask or endotracheal tube ventilation at birth of which most responded to the former4
Jonathan Wyllie MBChB FRCPCH is Consultant Neonatologist at the James
Cook University Hospital Marton Road Middlesbrough TS4 3BW UK
paeDiatRiCS anD CHilD HealtH 184 16
Sometimes it is possible to predict babies who are likely to have respiratory depression at birth and to have appropriate per-sonnel present at delivery Guidelines for attendance at deliveries will vary with institution but even when almost 40 of deliv-eries are attended there may still be a further 15 of babies who require unexpected resuscitation5 a proportion that seems to remain whatever changes are made
The physiology of babies requiring help at birth has been summarized previously167 It allows a logical approach to resus-citation (Figure 1) when evidence is lacking and may prompt further research
Resuscitation at birth
PreparationAt birth resuscitation is more likely in babies with intrapartum evidence of significant fetal compromise those less than 35 weeksrsquo gestation those delivering vaginally by the breech and in multiple births Personnel trained in newborn resuscitation should be available at every delivery1 Someone experienced in tracheal intubation and advanced resuscitation should also be easily available for normal low-risk deliveries in hospital and ideally in attendance for deliveries with an increased likelihood of needing resuscitation In the latter cases the equipment and environment can be prepared beforehand including a discussion with the parents Wash your hands put on gloves and consider what help may be needed
Cord clampingAt birth it has long been known that delay in clamping the cord will lead to less anaemia in babies and reduce subsequent iron deficiency8 However few hospitals have practised this interven-tion due to worries about hypothermia and the need to resusci-tate or stabilize babies In developed countries the advantages seemed to be outweighed by the potential disadvantages A recent randomized controlled study of delayed clamping of the cord in premature babies found that the intervention group had less late-onset sepsis and fewer intraventricular haemorrhages9 This is a low-risk strategy which needs further evaluation in order to introduce it without increasing other risk factors in pre-mature deliveries
Assessment and temperature controlAssessment and temperature control for the newborn baby should occur at all deliveries The assessment indicates the need for resuscitation Babies may vary from 23 to 40+ weeksrsquo ges-tation and in weight from 500 to 5000 g They are born naked and wet and if left cannot cope with an environmental tem-perature of less than 32degC However if the term baby is imme-diately dried put skin-to-skin with the mother and covered the delivery room temperature can be as low as 25ndash28degC Obviously the smaller the baby the greater the surface area to mass ratio and the greater the risk of hypothermia Compromised babies are particularly vulnerable10 and hypothermia will lower oxygen tension11 increase metabolic acidosis12 and inhibit surfactant production13
An effective method of maintaining the temperature of prema-ture babies less than 28 weeksrsquo gestation is wrapping them with plastic before drying and then placing them under a radiant
6 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Dry the babyRemove any wet towels and cover
Start the clock or note the time
Give 5 inflation breathsLook for a response
If no increase in heart rate look for chest movement
Re-check head positionApply Jaw thrust
Repeat inflation breathsLook for a response
If no increase in heart rate look for chest movement
Try alternative airway opening manoeuvresRepeat inflation breaths
Look for a response
If no increase in heart rate look for chest movement
If the heart rate is not detectable or slow (lt60)Start compressions
3 compressions to each breath
Reassess heart rate every 30 secondsConsider venous access and drugs
Assess colour tone breathing and heart rate
Open the airway
If not breathing
If still not breathing
If no response
If still no response
When the chest is moving
If meconium present
Baby breathing wellDo not suction the airway
Baby floppy and not breathing wellConsider inspection and suction before
inflation breaths
Head in neutral position
Inflation breathsUse a well-fitting face mask
connedted to a
pressure-limited gas supply
Each breath 2ndash3 seconds
duration at 30 cm H2O for a
term baby
Get help from a second personto support the airway andor
inspect the oropharynx under
direct vision and consider
suction andor insert an
oropharyngeal airway
Chest compressionsCompvent ratio 31
Rate 120 events per minute
Ensure the chest moves with each ventilation breath
If breathingReassess heart rate and monitor baby
If heart rate is satisfactory but increasingContinue ventilation breaths at about 30 per
minute until baby is breathing adequately
If heart rate is satisfactory but increasingContinue ventilation breaths at about 30 per
minute until baby is breathing adequately
If heart rate is increasingStop compressions
Continue ventilation breaths at about 30 per
minute until baby is breathing adequately
If the chest is not movingRecheck head position and repeat inflation
breaths If competent consider intubation
If the chest is still not movingThe airway is the problem
Figure 1 newborn life support (Courtesy of the Resuscitation Council uK)
heater14 There is a small risk of hyperthermia so the temperature must be monitored carefully
An assessment is made of the babyrsquos colour tone respira-tions and heart rate127 The most important of these is heart rate and a stethoscope is more reliable than cord pulsation15 How-ever saturation monitors may offer a more reliable assessment of both heart rate and colour16 but their interpretation requires a detailed knowledge of normal saturations at birth at differing gestations A baby who is apnoeic and floppy in the absence of neurological disease is unconscious and likely to be in terminal apnoea however this does not change the initial approach other
paeDiatRiCS anD CHilD HealtH 184 167
than the need to summon help early APGAR scores are never calculated to guide resuscitation
Airway
If a baby is in primary apnoea then with an open airway the first gasp will start to aerate the lungs and most babies will be able to lsquoresuscitatersquo themselves as shown in physiological stud-ies on animals Neutral positioning of the babyrsquos head chin lift jaw thrust oropharyngeal airways and endotracheal intubation may all be helpful in certain situations if performed correctly17
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Endotracheal intubationThe placement of an endotracheal tube has long been the gold standard of airway control and this remains true in the unconscious baby if it is correctly sized placed and fixed in a timely manner However experience is directly related to effec-tiveness in endotracheal intubation1819 and the success rate of less experienced clinicians such as a resident (STA1-3) or a fel-low (STA3-5) is lower varying between 33 and 68 Even senior neonatologists often take longer than guidelines recom-mend19 Experienced clinicians may judge correct endotracheal position visually or by an increase in heart rate with the first breaths but detection of exhaled carbon dioxide will give more rapid confirmation in larger babies12171920 and this can be par-ticularly useful for less experienced clinicians or those supervis-ing them However not all systems for the detection of exhaled carbon dioxide work in the smallest premature infants
Laryngeal masksLaryngeal masks may be effective for ventilating term newborn babies but there are few data for small premature infants There have been reports of dislodged laryngeal airways during paedi-atric arrests when chest compressions have been administered Although success of placement at first attempt by paediatri-cians is greater with a laryngeal mask than with an endotra-cheal tube21 the only and small randomized controlled trial in the delivery room favoured endotracheal intubation when per-formed by an anaesthetist22 Based mainly upon case reports the laryngeal mask can be recommended when positioning and mask ventilation and endotracheal intubation have failed to secure the airway but not as yet as a primary method of airway control
MeconiumIn 2000 Wisewell et al23 reported a large randomized controlled trial showing that tracheal intubation and suctioning of meco-nium-stained but vigorous babies at birth did not reduce the incidence or severity of meconium aspiration syndrome More recently another randomized trial has now shown that suction-ing on the perineum similarly offers no benefit24 Neither of these practices is recommended but intubation and suction of meconium from the trachea of non-vigorous babies born through meconium-stained liquor is still recommended
Breathing
In the apnoeic baby the first breaths establish the resting lung volume and aerate the fluid-filled alveoli This mechanical effect aided by surface tension within the alveoli causes the initial fall in pulmonary vascular resistance Experimentally this effect occurs even if the lungs are ventilated with nitrogen but is increased when air is used presumably due to the vasodilator effect of 21 oxygen The mechanical stretching of the lung also triggers the activation of cyclo-oxygenase beginning the production of prostacyclin Bradykinin is produced which has a further direct vasodilator effect and also possibly via prostacyclin Therefore adequate airway control and passive ventilation is vital not only because babies requiring resuscitation at birth have an almost uniformly respiratory aetiology but also in order to promote post-natal adaptation and reverse any maladaptation
paeDiatRiCS anD CHilD HealtH 184 16
In term babies peak ventilatory pressures of 20ndash30 cmH2O may be required but the minimal pressure needed to achieve an improvement in heart rate should be used or if there is no response chest wall movement Longer breaths at lower pressure may be more effective in displacing alveolar fluid and establish-ing the resting lung volume in lungs with sufficient surfactant and may improve initial oxygenation However premature new-borns are obviously physiologically and anatomically less pre-pared for delivery than infants at term Over-inflation has been implicated in histological lung damage in animal models and high tidal volumes appear to be equally damaging whether given before or immediately after administration of surfactant How-ever the same effect is not seen if these excessive tidal volumes are delivered 15 min after administration of surfactant2526 It is now thought that both excess end expiratory volume and inad-equate end-expiratory volume may cause lung damage2728 In premature infants it would therefore seem sensible to use lower pressures of 20ndash25 cmH2O12 delivered in a controlled way to prevent over-inflation and to apply positive end-expiratory pres-sure (PEEP) to prevent damage from under-inflation PEEP also improves both lung compliance and gas exchange2930 Without PEEP the airways collapse during the expiratory phase in animal models of newborn resuscitation
If animal data can be extrapolated it would also seem appro-priate to give surfactant as soon as possible to premature babies in order to ameliorate damage2526
The majority of newborn infants requiring resuscitation will re-establish regular respiration after administration of a few breaths which may be due to Headrsquos paradoxical reflex by which the inflation triggers an inspiratory effort
VentilationOnce the lungs are aerated if the newborn remains apnoeic ventilation should be continued at 30ndash60 breathsmin avoiding hyperventilation and using the minimum pressure possible to maintain a heart rate greater than 100 beatsmin
Face mask the majority of infants who require ventilation receive it via a face mask This may be attached to a bagvalve system with a spring lsquoblow offrsquo system or a lsquoT-piecersquo with a set flow and pressure It is important to realize that the bagvalve system is flow sensitive and that the harder the operator presses the greater the flow and the higher the delivered pressure In fact 60 cmH2O can be achieved with vigorous squeezing of a self-inflating bag Therefore it may be advantageous that most opera-tors are unlikely to be as effective as they suppose in creating a seal with the mask31 This is a skill that requires tuition and prac-tice31 In delivering a set pressure T-piece systems such as the Tom Thumbcopy or Neopuffcopy perform better than any bagminusvalve system but require a gas supply There is no evidence that lung compliance can be assessed using any bag system
Continuous airway pressure case series have suggested that early or delivery room use of continuous positive airway pres-sure (CPAP) in premature babies may reduce chronic lung dis-ease There have been two randomized trials of which one was a pilot study The data from the COIN trial do not show any advan-tage other than a reduction in intubation and surfactant use in the intervention group However an excess of pneumothorax
8 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
was also reported The Vermont Oxford Network and the SUP-PORT trials will provide further data but at present the delivery room use of CPAP cannot be widely recommended and should be limited to those units experienced in its use or taking part in research
Air or oxygen oxygen has been in widespread use for resuscita-tion at birth since the 1930s and even hyperbaric oxygen was seriously supported in the 1960s For many years there have been concerns about tissue damage from oxygen deprivation during and after resuscitation It became evident in the 1950s that unrestricted oxygen therapy could have serious conse-quences for future vision More recently concerns have been raised about potential adverse effects on respiratory physiology cerebral circulation and tissue damage from oxygen free radicals even during resuscitation A meta-analysis of four human studies demonstrated a reduction in mortality and no evidence of harm in infants resuscitated in air versus 100 oxygen3233 However there are several significant methodological concerns with these studies and the results should be interpreted with caution There is insufficient evidence to recommend any specific concentration of oxygen to be used for newborn resuscitation Monitoring the oxygen saturation of babies may be helpful but as yet there are no time-related normal target ranges and healthy term babies may take up to 10 min to achieve preductal oxygen saturation of greater than 95 and up to 60 min to achieve this postductally
There is therefore equipoise which would be open to an appropriate randomized controlled trial In the meantime the evidence only supports use of either 21 or 100 oxygen It is provoking to realize that if air had been in constant use since the 1930s there would be insufficient evidence for use of supple-mental oxygen
Circulation
Early resuscitation (temperature control airway breathing) provides oxygenated blood in the pulmonary arterioles which if returned to the heart causes the rate to increase34 If due to acidosis and hypoxia the circulation is ineffective then chest compressions may be needed They should be commenced when the heart rate remains below 60min despite effective airway and breathing management127 The best technique is using two hands to encircle the chest1 A ratio of three compressions to one breath is internationally accepted127 but has no evidence to support it Research has shown that neither compressions nor drugs will work in this situation without oxygenated blood so effective lung aeration and ventilation is essential A logical approach would be to fill the alveoli with air and to compress the chest until they are empty However training and teamwork require an agreed ratio which has therefore not changed since guidelines were first agreed internationally Success is assessed by an increase in heart rate which should therefore be assessed every 30 s Compressions stop when the spontaneous heart rate is greater than 60 beatsmin
In hypoxic newborn animal models successful resuscitation can restore cardiac output and blood pressure to levels above baseline within 5ndash10 min However it should be noted that there is a decline to 30 lower than basal levels within 2 h and that blood pressure is relatively spared suggesting an even greater
paeDiatRiCS anD CHilD HealtH 184 16
reduction in tissue perfusion This should be considered in the later care of any neonate who was hypoxic at birth
Drugs
Neonatal bradycardia at birth is almost always due to hypoxia plusmn acidosis and therefore drugs are rarely needed Adrenaline (epi-nephrine) is reported as being used in between 1 and 4 babies per 2000 births which is a large variation in practice Reported success is also variable and must be interpreted in light of this variation The use of drugs in extremely premature infants is con-troversial Some data suggested good outcomes for babies below 28 weeksrsquo gestation given adrenaline but these were flawed by high numbers of babies receiving resuscitative drugs some before the airway had been appropriately managed Audit data now suggest a poor outcome such that many clinicians would now council against the use of adrenaline and other drugs to resuscitate extremely premature newborn babies
Adrenaline (epinephrine)In 2003 a Cochrane review of randomized controlled trials involv-ing adrenaline use for resuscitation of neonates was unable to identify a single clinical trial35 Despite the lack of human neo-natal data animal models show the potential of adrenaline in asphyxial cardiac arrest and it is reasonable to use it when ade-quate ventilation and chest compressions have failed to increase the heart rate above 60 beatsmin Use 10ndash30 μgkg intrave-nously and preferably via an umbilical venous line The tracheal route cannot be recommended but if used it is likely that doses within this range will be ineffective and 100 μgkg might be tried However the safety of such doses has not been studied
BicarbonateThe use of bicarbonate has long been controversial but many of the concerns relate to the rapid correction of acidosis in neonates after resuscitation or the routine use of bicarbonate infusion nei-ther of which can be advocated There are no published human neonatal data to support its use although some exist from animal studies Animal data have also shown that the binding of adren-aline to receptors in the myocardium is significantly impaired by lactic acidosis and recent work on human lymphocyte beta-adrenergic receptors supports this view Whether this is also true of the more important alpha receptors is unknown In practice reversing intracardiac acidosis may improve myocardial function and assist in achieving a return of spontaneous circulation 1ndash2 mmolkg of bicarbonate may be given but this remains a contro-versial area
VolumeVolume expansion should only be given when it is suspected that the baby has suffered blood loss or the infant appears to be in shock (pale poor perfusion weak pulse) and has not responded adequately to other resuscitative measures If there is no history suggestive of blood loss shock is most likely to be due to myo-cardial dysfunction in which case fluids should be administered cautiously The most logical replacement fluid would be blood but in its absence isotonic crystalloid rather than albumin is the solution of choice given in 10 mlkg aliquots and observing the response Three randomized trials in neonates have shown
9 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
isotonic crystalloid to be as effective as albumin for the treat-ment of hypotension but none has examined either the relative or actual effectiveness in resuscitation A recent blinded randomized study comparing normal saline albumin or no volume expansion in a normovolaemic asphyxiated neonatal animal model showed that volume expansion was not beneficial and made a number of parameters worse36
NaloxoneNaloxone is not recommended as part of the initial resuscita-tion of newborns with respiratory depression Before it is given supporting ventilation should have restored the heart rate and colour The dose is 100 μgkg intravenously or intramuscularly Tracheal administration cannot be recommended Although administration of naloxone to neonates who have been exposed to maternal opioids during labour is a practice of long-standing it lacks the proper evidence of efficacy
Non-response to resuscitation
There are few more frightening situations professionally than applying the correct interventions in resuscitating or stabilizing a baby and getting no response Each stage must be adequately performed before moving onto the next and this requires regular reassessment When experienced help is needed at a newborn resuscitation it is usually the airway and ventilation that require correction If the heart rate does not increase this usually means that the lungs have not been successfully aerated In some cases however it may mean that the heart cannot respond as the cir-culation is inadequate In this situation the only way to check that the lungs have been successfully aerated is to see the chest move with ventilation or to obtain evidence of ventilation from a detector of exhaled carbon dioxide If you do not see chest movement after another five breaths the most likely cause is an obstructed airway either due to incorrect positioning or because the jaw has not been drawn forwards An oropharyngeal airway can be very helpful at this point especially in the term baby Only very occasionally is the airway blocked by mucus vernix blood or meconium but if the airway is guaranteed and there is no heart rate response or chest movement this should be sought by direct suction of the trachea even in the absence of any meconium staining of liquor Pneumothoraces can occur spontaneously after delivery but are rare at resuscitation carried out with pressure-limited devices Equally rare are diaphragmatic hernias that have not been diagnosed antenatally giving problems at resuscitation
If the chest is moving but the heart rate has not responded to resuscitation consider rare possibilities such as fetal blood loss pneumothorax or heart block (mothers with undiagnosed systemic lupus erythematosis delivered for fetal bradycardia) as possibilities With adequate ventilation there is no evidence of oxygen concentrations less than 100 being responsible for prolonged bradycardia or failure to respond although current practice would support increasing the delivered oxygen concen-tration if resuscitation had been commenced using air
Outcome
The prognosis for the full-term baby subjected to sudden acute asphyxia is usually good provided the episode does not last for
paeDiatRiCS anD CHilD HealtH 184 17
long Most babies resuscitated from primary apnoea have no sequelae secondary to the resuscitation Many babies who start to breathe again regularly within 20 min of the circulation being restored recover completely but it is rare for a baby who is still gasping after 30 min to recover
The prognosis for the preterm baby of less than about 34 weeksrsquo gestation subjected to severe acute anoxia is less predict-able This is because of the risk of secondary intraventricular haemorrhage or periventricular intracerebral haemorrhage andor infarction after even a relatively brief asphyxial episode espe-cially in the period immediately around birth
The effects of chronic hypoxia are also difficult to predict but a reasonably clear idea of the extent of the problem should be obtainable within 36ndash48 h of the original chronic asphyxial insult A mild short-lasting state of hyperexcitability usually car-ries a good prognosis even if there is seizure activity but more severe symptoms can be associated with permanent handicap This is seen especially in infants with encephalopathy requiring ventilation
REFERENCEs
1 Biarent D Bingham R Richmond S et al european Resuscitation
Council guidelines for Resuscitation 2005 Section 6 paediatric life
support Resuscitation 2005 67(suppl 1) S97ndashS133
2 international liaison Committee on Resuscitation part 7 neonatal
resuscitation Resuscitation 2005 67 293ndash303
3 Singh J Santosh S Wyllie J mellon a effects of a course in
neonatal resuscitation - evaluation of an educational intervention
on the standard of neonatal resuscitation Resuscitation 2006 68
385ndash389
4 palme-Kilander C methods of resuscitation in low-apgar-score
newborn infants - a national survey Acta Paediatr 1992 81
739ndash744
5 Kroll l twohey l Daubeney p et al Risk factors at delivery and
the need for skilled resuscitation Eur J Obstet Gynecol Reprod Biol
1994 44 175ndash177
6 Wyllie Jp Resuscitation of the newborn The Foundation Years
2007 3(4) 153ndash157
7 Richmond S ed newborn life Support Resuscitation at Birth
london Resuscitation Council 2006
8 Ceriani Cernadas Jm Carroli g pelligrine l et al the effect of timing
of cord clamping on neonatal venous hematocrit values and clinical
outcome at term a randomized controlled trial Pediatrics 2006
117 e779ndashe786
9 mercer JS Vohr BR mcgrath mm padbury JF Wallach m oh W
Delayed cord clamping in very preterm infants reduces the incidence
of intraventricular hemorrhage and late-onset sepsis a randomized
controlled trial Pediatrics 2006 117 1235ndash1242
10 Dahm lS James lS newborn temperature and calculated heat loss
in the delivery room Pediatrics 1972 49 504ndash513
11 Stephenson J Du J tk o the effect of cooling on blood gas
tensions in newborn infants J Pediatr 1970 76 848ndash852
12 gandy gm adamsons Jr K Cunningham n Silverman Wa James lS
thermal environment and acid-base homeostasis in human infants
during the first few hours of life J Clin Invest 1964 43 751ndash758
13 gluck l Kulovich mV eidelman ai et al Biochemical development
of surface activity in mammalian lung pulmonary lecithin synthesis
0 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
in the human fetus and newborn and etiology of the respiratory
distress syndrome Pediatr Res 1972 6 81ndash99
14 Vohra S Roberts RS Zhang B Janes m Schmidt B Heat loss
prevention (Help) in the delivery room a randomised controlled
trial of polyethylene occlusive skin wrapping in very preterm infants
J Pediatr 2004 145 750ndash753
15 owen CJ Wyllie Jp Determination of heart rate in babies at birth
Resuscitation 2004 60 213ndash217
16 orsquoDonnell Cp Kamlin Co Davis pg Carlin JB morley CJ Clinical
assessment of infant colour at delivery Arch Dis Child Fetal
Neonatal Ed 2007 92 F465ndashF467
17 international liaison Committee on Resuscitation part 13 neonatal
Resuscitation guidelines Circulation 2005 112(suppl 24)
iV188ndashiV195
18 leone ta Rich W Finer nn neonatal intubation Success of
pediatric trainees J Pediatr 2005 146 638ndash641
19 orsquoDonnell Cp Kamlin Co Davis pg morley CJ endotracheal
intubation attempts during neonatal resuscitation success
rates duration and adverse effects Pediatrics 2006 117
e16ndash21
20 Repetto Je Donohue pa-CpK Baker SF Kelly l nogee lm use of
capnography in the delivery room for assessment of endotracheal
tube placement J Perinatol 2001 21 284ndash287
21 gandini D Brimacombe JR neonatal resuscitation with laryngeal
mask airway in normal and low birth weight infants Anesth Analg
1999 89 642ndash643
22 esmail n Saleh m ali a laryngeal mask airway versus endotracheal
intubation for apgar score improvement in neonatal resuscitation
Egypt J Anesthiol 2002 18 115ndash121
23 Wiswell te gannon Cm Jacob J et al Delivery room management
of the apparently vigorous meconium-stained neonate results of
the multicenter international collaborative trial Pediatrics 2000
105 1ndash7
24 Vain ne Szyld eg prudent lm Wisewell te aguilar am Vivas ni
oropharyngeal and nasopharyngeal suctioning of meconium-stained
neonates before delivery of their shoulders multicentre randomised
controlled trial Lancet 2004 364 597ndash602
25 Bjorklund lJ ingimarsson J Curstedt t larsson a Robertson B
Werner o lung recruitment at birth does not improve lung function
in immature lambs receiving surfactant Acta Anaes Scand 2001 45
986ndash993
26 Bjorklund lJ ingimarsson J Curstedt t et al manual ventilation
with a few large breaths at birth compromises the therapeutic effect
of subsequent surfactant replacement in immature lambs Pediatr
Res 1997 42 348ndash355
paeDiatRiCS anD CHilD HealtH 184 17
27 taskar V John J evander e Robertson B Jonson B Surfactant
dysfunction makes lungs vulnerable to repetitive collapse and re-
expansion Am J Respir Crit Care Med 1997 155 313ndash320
28 muscedere Jg mullen JB gan K Slutsky aS tidal ventilation at low
airway pressures can augment lung injury Am J Respir Crit Care Med
1994 149 1327ndash1334
29 nilsson R grossman g Robertson B Bronchiolar epithelial lesions
induced in the premature rabbit neonate by short periods of artificial
ventilation Acta Pathol Microbiol Scand 1980 88 359ndash367
30 probyn me Hooper SB Dargaville pa et al positive end expiratory
pressure during resuscitation of premature lambs rapidly improves
blood gases without adversely affecting arterial pressure Pediatr
Res 2004 56 198ndash204
31 Wood Fe morley CJ Dawson Ja et al improved techniques
reduce face mask leak during simulated neonatal resuscitation
study 2 Arch Dis Child Fetal Neonatal Ed in press doi101136
adc2007117788
32 tan a Schulz a orsquoDonnell CpF Davis pg air versus oxygen for
resuscitation of infants at birth Cochrane Database Syst Rev 2004
(3) CD002273
33 Davis pg tan a orsquoDonnell Cp Schulze a Resuscitation of newborn
infants with 100 oxygen or air a systematic review and meta-
analysis Lancet 2004 364 1329ndash1333
34 Dawes g Fetal and neonatal physiology Chicago year Book
publisher 1968 p 141ndash159
35 Ziino aJa Davies mW Davis pg epinephrine for the resuscitation
of apparently stillborn or extremely bradycardic newborn infants
Cochrane Database Syst Rev 2003 (2) CD003849
36 Wyckoff m garcia D margraf l perlman J laptook a Randomized
trial of volume infusion during resuscitation of asphyxiated neonatal
piglets Pediatr Res 2007 61 415ndash420
Practice points
bull Resuscitation at birth is different from that at all other times
of life
bull a standard approach can be applied to most newborn
resuscitation
bull guidelines are based on a rigorous evaluation of evidence
where possible
bull evidence is sparse but evolving
bull most preterm babies require stabilization rather than
resuscitation
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Acidndashbase physiology and blood gas interpretation in the neonateSusern tan
morag Campbell
Abstractacidndashbase balance describes the complex processes that work to main-
tain a stable extracellular pH for optimal cellular function the process
of balancing the production and neutralization of tissue acid provides a
great challenge for newborn infants who have significantly higher rates
of acid production than adults Factors which help maintain a stable
acidndashbase balance include buffers the respiratory system and renal sys-
tem Both intracellular and extracellular buffers resist changes in pH
the most important extracellular buffer system for maintaining stable
pH is the bicarbonate system in response to acidosis or alkalosis the
respiratory system balances the production of acid with the clearance
of Co2 by altering respiratory rate the kidneys provide a delayed but
sustained response to pH imbalance by excreting either acidic or alkaline
urine in response to systemic acidosis and alkalosis respectively in sick
premature infants these systems have a limited capacity completely to
control pH this review discusses the physiology of the three systems
which control acidndashbase balance patterns of clinical abnormalities in
acidndashbase status and their underlying causes are discussed We present
a systematic approach to blood gas analysis and interpretation in new-
born infants
Keywords acidosis alkalosis bicarbonate bloodndashgas analysis
metabolic pH
Introduction
Blood gas analysis is a routine procedure performed on newborn babies receiving respiratory support in the neonatal intensive care The combination of invasive and non-invasive assessment of ventilation and oxygenation enables clinicians appropriately to modify respiratory care according to each individual babyrsquos rapidly changing clinical status
Understanding the fundamentals of acidndashbase balance helps us to use blood gas analysis not only to assess respiratory sta-tus but also to provide information on metabolic status and the adequacy of tissue perfusion
Susern Tan MBBS MRCP is Clinical Fellow at the Neonatal Intensive Care
Unit 6th Floor North Wing St Thomasrsquo Hospital London SE1 7EH UK
Morag Campbell MBChB MRCP is Consultant Neonatologist at the
Neonatal Intensive Care Unit 6th Floor North Wing St Thomasrsquo
Hospital London SE1 7EH UK
paeDiatRiCS anD CHilD HealtH 184 17
What is understood by acid-base balance
Acidndashbase balance refers to the complex physiological processes used by the body to maintain a stable extracellular pH1 A serum pH within the range of 735ndash745 provides the ideal environment for cellular metabolism Maintaining a stable pH is critical as the metabolic activity of proteins is pH dependent and small changes in hydrogen ion (H+) concentration can potentially alter physio-logical function
Acids are substances that yield free H+ in solution while a base accepts H+ and in solution combines with an acid to neu-tralize it In the normal metabolic state H+ are continuously pro-duced and neutralized to maintain a steady pH balance12 The rate of H+ production is two to three times higher in neonates because of their rapid growth rates and increased acid production from protein turnover and bone mineralization The challenge of maintaining a stable pH through processing and neutralizing H+ is therefore greatest in newborn infants
Using exact values of H+ concentration to assess acidndashbase status is cumbersome and it is more commonly expressed as pH defined by the equation
pH = minuslog H+
Maintaining acidndashbase balance
The balance between production and excretion of acids in the body is controlled by buffer systems which have an immediate effect and by the respiratory and the renal systems
Buffer systemsBuffer solutions resist change in pH when acid or alkali is added due to their capacity to absorb or give up H+ The three main buffer systems in the body are the bicarbonate phosphate and protein systems1ndash3 The protein and phosphate buffer systems are intracellular and act as lsquosinksrsquo for extracellular H+ which are exchanged with intracellular potassium (K+) and sodium ions (Na+) In an acute metabolic acidosis hyperkalaemia may develop due to this H+ exchange4
The bicarbonate buffer system is extracellular and consists of a mixture of carbonic acid (H2CO3) and sodium bicarbon-ate (NaHCO3) This buffer system helps maintain a stable pH by soaking up excess H+ with HCO3
minus which in solution forms carbonic acid (H2CO3) Carbonic acid is a weak acid and readily dissociates to give CO2 which is transported in dissolved form to the lungs for excretion
H+ + HCO3minus harr H2CO3 harr H2O + CO2
The bicarbonate system therefore completes the neutraliza-tion of excess H+ and a stable plasma pH is maintained The relationships between pH HCO3
minus and CO2 in this system are described by the HendersonndashHasselbalch equation15
pH = 61 + log HCO3minus003 times CO2
where 61 is the log of the dissociation coefficient of carbonic acid and 003 the solubility of CO2 in plasma Buffers are most potent when there are equal amounts of H+ and HCO3
minus in solution The
2 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
bicarbonate system is not a potent buffer however as HCO3minus
and CO2 are readily altered by the body this system plays a very powerful role in pH homeostasis15
Respiratory regulationThe respiratory system adapts within minutes to hours as part of the acute response to acidosis This system modifies pH by balancing production of H+ with ventilatory clearance of CO2
H+ directly stimulates chemoreceptors in the respiratory cen-tre of the brainstem producing an increase in respiratory rate26 The response to respiratory acidosis is very rapid as CO2 easily diffuses across the bloodndashbrain barrier however in metabolic acidosis compensation is delayed until plasma bicarbonate fully equilibrates with cerebrospinal fluid (CSF) bicarbonate There is an inverse relationship between alveolar ventilation and partial pressure of dissolved carbon dioxide (PaCO2) a reduction in alveolar ventilation raises PaCO2 and decreases pH Changes in pH therefore affect alveolar ventilation and conversely changes in alveolar ventilation cause significant changes in pH
Renal regulationThe kidneys provide a delayed but sustained response to acidndashbase imbalances by excreting either acidic or alkaline urine In full-term and preterm babies the capacity for acid excretion and bicarbonate reabsorption is reduced as glomerular filtration rates are low and tubular function immature7 Renal function matures with gestation postnatal age and glucocorticoid and thyroid hormones78 Due to their limited capacity to preserve HCO3
minus newborn infants have lower serum bicarbonate levels and are predisposed to acidosis7
Bicarbonate is not effectively reabsorbed due to its size and electrical charge Instead intraluminal HCO3
minus combines with secreted H+ in tubular luminal fluid to produce carbonic acid which dissociates to give H2O and CO2 This CO2 diffuses into tubular cells combines with intracellular H2O and forms carbonic acid which liberates HCO3
minus and H+ HCO3minus is then
recovered to the circulation by exchange for chloride ions (Clminus) through the basal cell membrane247
Renal acid secretion occurs at all sites except the loop of Henle Primary active transport accounts for 5 and secondary for the remaining 95 of total H+ excretion Secondary trans-port involves an exchange between luminal Na+ and intracel-lular H+ Both ions bind to a membrane transport protein The Na+ concentration gradient between the tubular lumen and cells enables Na+ drag into the cell which generates energy to fuel active H+ excretion into the tubular lumen1ndash47
Quantifying acidosis
Standard base excess is a calculated value derived from PaCO2 and pH It is expressed as the mmollitre of base above or below normal buffer bases required to correct the pH to 74 at a PaCO2 of 40 mmHg A negative base excess or base deficit indicates an acidosis while a positive base excess indicates a relative alkalosis15
Anion gap is the measured difference between anions and cations in the blood
Anion gap = (Na+ + k+) minus (HCO3+Clminus)
paeDiatRiCS anD CHilD HealtH 184 17
Calculation of the anion gap enables clinicians better to define the underlying cause of a metabolic acidosis9 The common causes of an increased anion gap acidosis in neonates include lactic acidosis due to tissue hypoperfusion and hypoxia it may also be seen with certain inborn errors of metabolism and in uraemia910 The anion gap can help distinguish between the rela-tively benign non-anion gap hyperchloraemic acidosis seen in premature infants and a pathological lactic acidosis due to poor end-organ perfusion1011
Strong ion theory
Stewart described a complex acidndashbase model which proposed that H+ concentration results from the dissociation of water which is influenced by PaCO2 the strong ion difference and plasma weak acids12
Strong ions are ions that dissociate at normal body pH and include Na+ K+ and Clminus Weak acids in plasma which contrib-ute include albumin inorganic phosphate and plasma proteins their concentrations do not change with pH and are therefore a constant The effect of these factors and other unmeasured tissue ions on acidndashbase status can be quantified by the calculation of the strong ion gap (SIG)112 In the neonatal unit it is perhaps more important that we consider how principles of this model may relate to acidndashbase status rather than fully to quantify the SIG Theoretically low albumin and phosphate levels which fre-quently occur in premature infants by reducing the concentra-tion of weak acids can produce a relative alkalosis while high phosphate levels in renal failure may contribute to acidosis
Tissue oxygenation
Oxygenation is closely linked to acidndashbase status as optimal cel-lular function requires oxygen to fuel aerobic metabolism and produce energy In hypoxic conditions anaerobic metabolism predominates which is energy inefficient and results in a lactic acidosis1011
Tissue oxygen availability is related to regional blood flow haemoglobin level and haemoglobin oxygen affinity Arterial blood gases measure the partial pressure of dissolved oxygen (PaO2) which represents a small component of total oxygen con-tent the majority being transported bound to haemoglobin The relationship between percentage haemoglobin saturation (SaO2) and PaO2 is described by the sigmoidal oxyhaemoglobin disso-ciation curve which enables us to relate the two measures to each other235 The affinity of haemoglobin for oxygen is altered by local tissue factors Increases in temperature H+ PaCO2 and 23-diphosphoglycerate (DPG) levels shift the oxyhaemoglobin dissociation curve to the right reducing affinity for oxygen Decreases in temperature H+ PaCO2 and 23-DPG levels shift the curve to the left increasing oxygen affinity1ndash35 In the body haemoglobin oxygen affinity continuously changes increasing in the lungs to enable efficient oxygen uptake and decreasing at tissue level to provide efficient oxygen delivery to metabolically active tissues
Avoiding both hypoxia and hyperoxia is important in the neo-natal unit as deleterious effects of hypoxia are seen in infants with pulmonary hypertension1314 while hyperoxia is associated with an increased incidence of retinopathy of prematurity1516
3 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Clinical acidndashbase imbalances
Clinical acidndashbase imbalances can be respiratory metabolic or a mixture of both These abnormalities may be corrected by the acidndashbase regulatory mechanisms in the body in an attempt to maintain normal pH (Figure 1)
Respiratory acidosisThis occurs when any disorder leads to decreased alveolar ventilation Common causes of respiratory acidosis are listed in Table 1 Reduced respiratory clearance of CO2 means more dissolved CO2 accumulates in the plasma leading to increased production of carbonic acid and H+ Through chemoreceptor stimulation respiratory acidosis rapidly alters ventilation in an attempt to reduce CO226 Chemoreceptor mediated ventila-tory increases may only partly adjust in premature infants with underlying lung disease In babies with a sustained respiratory acidosis eg in chronic lung disease then metabolic compen-sation occurs through increased renal excretion of H+ and reabsorption of HCO3
minus slowly restoring pH to around 80 of normal47
paeDiatRiCS anD CHilD HealtH 184 17
The management of PaCO2 levels in infants receiving mechan-ical ventilation has important clinical implications Premature babies have impaired cerebral autoregulation17 and adverse neurological sequelae are reported in association with high PaCO2 levels18ndash20 Ventilation strategies which advocate lsquoper-missive hypercarbiarsquo have been developed to minimize airways damage from mechanical ventilation21 Published data suggest pulmonary benefits however the safe level of PaCO2 remains to be defined in premature infants2021
Respiratory alkalosisThis occurs when more CO2 is excreted than is produced by the body Pathological conditions leading to respiratory alkalosis are rare Hyperventilation in the neonatal setting is often iatrogenic or may be due to disorders in brainstem control of breathing including hypoxicndashischaemic encephalopathy or primary central nervous system abnormalities (see Table 1)
If respiratory alkalosis is sustained it may be compensated for by reduced reabsorption of filtered bicarbonate Reported adverse associations of low PaCO2 include periventricular leuco-malacia and intraventricular haemorrhage1922
K+
H+
Overventilation
CO2 + H2O harr H2CO3 harr H+ + HCO3ndash
Bicarbonate Buffer
Intracellular Buffer
uarr H+ excretionuarr HCO3
ndash absorption
uarr buffered H+
(NH4+ H2PO4
ndash)uarr ventilation rate
RespiratoryAcidosis
MetabolicAcidosis
darr CO2and uarr pH
RespiratoryAlkalosis
MetabolicAlkalosis
darr H+ anduarr pH
darr ventilation rate
uarrCO2
and darr pH
darr H+ excretiondarr HCO3
ndash absorption
uarrH+ and
darr pH
Brain
Brain
Intracellular Buffer
H+
K+
Sepsis
HypoxiaRDS
Metabolismand growth
Diuretics
Airwayobstruction
Neuromuscularproblems
IEM
Gastric losses
+ +
ndash -
Renal BufferRespiratory Buffer
Figure 1 mechanisms for regulation of extracellular pH iem inborn errors of metabolism RDS respiratory distress syndrome
4 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Common causes of acidndashbase imbalances
pH PCO2 H2CO3 Base excess Common neonatal causes
Respiratory acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
uarr normal normal bull upper airway obstruction choanal atresia
pierre-Robin sequence
bull lung abnormalities respiratory distress
syndrome transient tachypneoa of
newborn pneumonia meconium aspiration
syndrome pulmonary hypoplasia
congenital pulmonary malformations
bull Central hypoventilation hypoxic-ischaemic
encephalopathy intracranial haemorrhage
bull neuromuscular insufficiency congenital
myopathies congenital neuropathies
bull iatrogenic inadequate ventilatory settings
Compensated lower limit
of normal
uarr uarr gt+3
metabolic acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
normal darr ltminus3 increased anion gap
bull lactic acidosis sepsis hypoperfusion
shock necrotizing enterocolitis
bull inorganic acidosis inborn errors of
metabolism renal failure
normal anion gap
bull increased gastrointestinal H2Co3 losses
ileostomy diarrhoea
bull Renal tubular acidoses
Compensated lower limit
of normal
darr darr ltminus3
Respiratory alkalosis Uncompensated gt 745 darr normal normal bull iatrogenic excessive ventilatory settings
bull Compensatory hyperventilation hypoxic-
ischaemic encephalopathy
Compensated higher limit
of normal
darr darr ltminus3
metabolic alkalosis Uncompensated gt 745 normal uarr gt+3 bull gastric losses vomiting non-replacement
of excessive nasogastric aspirates
bull thiazide and loop diuretics
bull Hypokalaemia
Compensated higher limit
of normal
uarr uarr gt+3
Table 1
Metabolic acidosisThis frequently affects infants in the neonatal unit and has many causes1011 (see Table 1) There may be overproduction of tissue acid impaired acid clearance gastrointestinal loss of bicarbonate or an exogenous increased acid load eg chloride total paren-teral nutrition (TPN) or albumin1ndash323
Calculation of the anion gap to distinguish an increased anion gap acidosis from a non-anion gap acidosis is important both for treatment and prognosis1011 Acidosis stimulates respiratory compensation but this is limited in unstable infants Similarly renal compensation with improved HCO3
minus conservation is con-strained by tubular immaturity Treatment of the acidosis should be directed at the underlying cause eg hypoxia hypotension or excess Clminus rather than by administration of base
Metabolic alkalosisThis is unusual in neonates and is most frequently seen in infants with chronic lung disease or heart failure who are receiving diuretics Diuretics cause alkalosis by increasing renal fluid and Na+ losses An active process to reabsorb Na+ occurs in tubule cells which through enhanced H+ secretion and HCO3
minus reab-sorption produce alkalosis27
paeDiatRiCS anD CHilD HealtH 184 17
Metabolic alkalosis may also occur with excessive loss of gas-tric contents eg protracted vomiting or inadequate replacement of nasogastric aspirates (see Table 1)
Interpreting blood gases
Blood gas measurements can provide important diagnostic and prognostic information and a systematic approach to blood gas analysis is described in Table 2 The clinical management of infants with abnormal gases requires a good understanding of acidndashbase physiology and tissue oxygenation and an apprecia-tion of factors which may affect the reliability of samples
Arterial blood sampling is the gold standard however indwelling arterial catheters and arterial stab samples are usually restricted to infants who are critically ill or those who require sig-nificant ongoing intervention Gases are most frequently measured in capillary or venous samples which correlate well with arterial samples for PaCO2 pH and base excess in babies and children receiving intensive care These correlations however are not valid in infants with peripheral vasoconstriction and hypotension2324
Non-invasive monitoring techniques may enable us to reduce the frequency of blood gas sampling Transcutaneous monitoring
5 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
A systematic approach to blood gas analysis
1 Collect the relevant information
bull type of gas ndash capillary or arterial
bull Current respiratory support ndash document level
bull transcutaneous Co2 and Sao2 levels
bull Clarify no significant clinical events before sampling
2 pH accept a range between 730 and 745 in newborn
babies this is lower than in older children is there an
alkalosis (pH gt 745) or an acidosis (lt 730)
3 Co2 aim for a range between 45 and 65 kpa a paCo2 level
more than 65 kpa suggests inadequate alveolar ventilation
while less than 45 kpa suggests hyperventilation Correlate
values with non-invasive measures
4 o2 Can only be assessed from arterial gases aim for pao2
between 60 and 80 kpa Correlate results with pulse
oximetry levels
5 HCo3 and base excess normal HCo3 level is between 20 and
24 mmollitre and bases excess +3 to minus3
6 anion gap look at the anion gap and lactate to help identify
the cause of an acidosis normal lactate levels should be less
than 2 mmollitre
7 Respiratory or metabolic compensation look at the pH and
assess whether it is appropriate for the Co2 level or is there
evidence of compensation
8 interpret use both the clinical history and blood gas
findings to help you identify the primary problem aim your
management at treating the underlying cause
9 Reassess if clinical management changes have been made
repeat the blood gas after an appropriate time interval to
ensure improvement
Table 2
provides a highly accurate and reliable method for measuring PaCO2 through the skin it can however be technically difficult may cause tissue damage and is of limited reliability when peripheral perfusion is reduced25 Continuous end-tidal CO2 measurements correlate well with arterial CO2 values in patients with normal ventilation and perfusion however in babies with lung disease alveolar collapse small tidal volumes and rapid respiratory rates can make these measurements unreliable26 Despite its limitations transcutaneous monitoring provides the best method for CO2 trend monitoring in the neonatal intensive care unit (NICU)25
Oxygen saturation levels can be continuously measured non-invasively using pulse oximetry While oximetry is easy to perform and accurate on occasion SaO2 levels obtained may be unreliable when tissue perfusion is poor or with movement artefact SaO2 monitoring is highly sensitive at detecting hypoxia but is limited in detecting hyperoxia as at levels more than 90 small changes in SaO2 may result in unacceptably large increases in PaO227 It is therefore essential that SaO2 alarm limits are set for all neonates receiving respiratory support to detect hypoxia and prevent hyperoxia1627
Continuous non-invasive monitoring provides invaluable information when managing complex infants in the NICU but it does not replace the need for regular blood gas analysis
paeDiatRiCS anD CHilD HealtH 184 17
ReFeRenCeS
1 Kellum Ja Determinants of blood pH in health and disease
Crit Care 2000 4 6ndash14
2 Quigley R Baum m neonatal acid base balance and disturbances
Semin Perinatol 2004 28 97ndash102
3 Brouillette Rt Waxman DH evaluation of the newbornrsquos blood gas
status Clin Chem 1997 43 215ndash221
4 Chan JC acid-base disorders and the kidney Adv Pediatr 1983 30
401ndash471
5 Siggaard-andersen o the pH-log pCo2 blood acidndashbase nomogram
revised Scand J Lab Invest 1962 14 598ndash604
6 Saetta m mortola Jp interaction of hypoxic and hypercapnic stimuli
on breathing pattern in the newborn rat J Appl Physiol 1987 62
506ndash512
7 Baum m Quigley R postnatal renal development in Seldin DW
giebisch g eds the kidney physiology and pathophysiology new
york lippincott Williams and Wilkins 2000 p 703ndash726
8 ortiz la Quan a Weinberg a et al effect of prenatal
dexamethasone on rat renal development Kidney Int 2001 59
1663ndash1669
9 gabow pa Kaehny WD Fennessey pV goodman Si gross pa
Schrier RW Diagnostic importance of an increased serum anion gap
N Engl J Med 1980 303 854ndash858
10 lorenz Jm Kleinman li markarian K oliver m Fernandez J Serum
anion gap in the differential diagnosis of metabolic acidosis in
critically ill newborns J Pediatr 1999 135 751ndash755
11 Deshpande Sa platt mp association between blood lactate and
acid-base status and mortality in ventilated babies Arch Dis Child
1997 76 F15ndash20
12 Stewart pa modern quantitative acid-base chemistry Can J Physiol
Pharmacol 1983 61 1444ndash1461
13 Dakshinamurti S pathophysiologic mechanisms of persistent
pulmonary hypertension of the newborn Pediatr Pulmonol 2005
39 492ndash503
14 mourani pm ivy DD gao D abman SH pulmonary vascular
effects of inhaled nitric oxide and oxygen tension in
bronchopulmonary dysplasia Am J Respir Crit Care Med 2004
170 1006ndash1013
15 Deulofeut R Critz a adams-Chapman i Sola a avoiding hyperoxia
in infants le 1250 g is associated with improved short- and long-
term outcomes J Perinatol 2006 26 700ndash705
16 Chow lC Wright KW Sola a Can changes in clinical practice
decrease the incidence of severe retinopathy of prematurity in very
low birth weight infants Pediatrics 2003 111 339ndash345
17 Boylan gB young K panerai RB Rennie Jm evans DH Dynamic
cerebral autoregulation in sick newborn infants Pediatr Res 2000
48 12ndash17
18 Kaiser JR gauss CH pont mm Williams DK Hypercapnia during
the first 3 days of life is associated with severe intraventricular
hemorrhage in very low birth weight infants J Perinatol 2006 26
279ndash285
19 Fabres J Carlo Wa phillips V Howard g ambalavanan n Both
extremes of arterial carbon dioxide pressure and the magnitude of
fluctuations in arterial carbon dioxide pressure are associated with
severe intraventricular hemorrhage in preterm infants Pediatrics
2007 119 299ndash305
20 thome uH Carroll W Wu tJ et al outcome of extremely preterm
infants randomized at birth to different paCo2 targets during the
first seven days of life Biol Neonate 2006 90 218ndash225
6 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
21 Carlo Wa Stark aR Wright ll et al minimal ventilation to prevent
bronchopulmonary dysplasia in extremely-low-birth-weight infants
J Pediatr 2002 141 370ndash374
22 okumura a Hayakawa F Kato t et al Hypocarbia in preterm
infants with periventricular leukomalacia the relation between
hypocarbia and mechanical ventilation Pediatrics 2001 107
469ndash475
23 peters o Ryan S matthew l Cheng K lunn J Randomised
controlled trial of acetate in preterm neonates receiving parenteral
nutrition Arch Dis Child 1997 77 F12ndash15
24 yildizda D yapiciolu H yilmaz Hl Sertdemir y Correlation of
simultaneously obtained capillary venous and arterial blood gases
of patients in a paediatric intensive care unit Arch Dis Child 2004
89 176ndash180
25 aliwalas ll noble l nesbitt K et al agreement of carbon
dioxide levels measured by arterial transcutaneous and end tidal
methods in preterm infants 28 weeks gestation J Perinatol 2005
25 26ndash29
26 Hagerty JJ Kleinman me Zurakowski D et al accuracy of a new
low-flow sidestream capnography technology in newborns a pilot
study J Perinatol 2002 22 219ndash225
paeDiatRiCS anD CHilD HealtH 184 17
27 poets CF Wilken m Seidenberg J Southall Dp von der Hardt H
Reliability of a pulse oximeter in the detection of hyperoxemia
J Pediatr 1993 122 87ndash90
Practice points
bull a stable extracellular pH is important for optimal cellular
functioning
bull abnormalities in acidndashbase balance are regulated by buffer
systems and the respiratory and renal tract
bull maintaining a stable pH is challenging for newborn babies
due to their high rates of acid production and immature
regulatory mechanisms
bull arterial or capillary blood gases provide an effective way to
monitor acidndashbase balance in newborns
bull Blood gases should be analysed in a structured manner
assessing pH and then respiratory and metabolic components
bull the treatment of acidndashbase abnormalities should be directed
at the underlying problem not merely at correcting pH
7 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Recognition and management of neonatal seizuresmalcolm levene
AbstractSeizures are the most common major manifestation of central nervous
system dysfunction in the newborn there are many causes but perina-
tal asphyxia and haemorrhagicinfarction lesions account for about 75
there is now considerable evidence that frequent but short seizures in
the neonate affect subsequent neurodevelopmental outcome Studies
using eeg or modified continuous tracing of eeg activity (aeeg or CFm)
have shown that there is often electroconvulsive dissociation this re-
fers to poor correlation between electrical seizures and clinical seizures
Commonly used anticonvulsants appear to increase electroconvulsive
dissociation effective management of neonatal seizures has proved very
disappointing and less than 50 of seizures are abolished by first-line
anticonvulsant medication (phenobarbitone or phenytoin) Drugs such
as midazolam and lidocaine may further reduce seizures but require
more evaluation the challenge is to assess new and more effective anti-
convulsants which are themselves associated with little neurotoxicity
Keywords antiepileptic drugs eeg neonatal seizures neurodegeneration
Convulsions are the most common major neurological sign seen in newborn infants and their incidence estimated from large population studies is 26 per 1000 live births1 Premature infants are over four times more likely to have convulsions than full-term infants12 Neonatal status epilepticus (continuous seizure activity lasting 30 min or more) diagnosed clinically is rare and accounts for only 5 of infants with seizures1 although this is now recognized more frequently as the result of continuous EEG monitoring3
Neonatal convulsions are described as presenting in a num-ber of different ways and various seizure types can be seen in the same baby over a number of hours The frequencies of the various patterns of seizure activity are given in Table 1 In very premature babies and to a lesser extent in term infants minor movement abnormalities may be difficult to identify as subtle seizures These include lip smacking tongue thrusting mouth-ing pedalling type movements of the lower limbs or swimming movements of the arms Apnoea can be a common manifesta-tion of subtle seizures The signs can be protean and vary from baby to baby or even in the same baby Virtually any stereotypic
Malcolm Levene MD FMedSc FRCPCH FRCH is Professor and Head of
Department of Paediatrics and Child Health at University of Leeds Leeds
and Honorary Neonatologist at Leeds General Infirmary Leeds UK
paeDiatRiCS anD CHilD HealtH 184 178
movement may be a manifestation of a seizure disorder in the newborn
Aetiology
The more carefully the fitting baby is investigated the more likely it is that a cause for the seizures will be found A number of recent papers have described the aetiology of neonatal con-vulsions after extensive investigations14 Tekgul et al4 recently studied a consecutive group of full-term infants with evidence of neonatal convulsions (recognized both clinically and on EEG) and reported their outcome Table 2 summarizes these data as well as risk of moderate or severe disability for each causative factor Perinatal asphyxia is the commonest cause for convul-sions in term infants with haemorrhagic or ischaemic lesions also being common
Overall the prognosis for the group of term babies with con-vulsions was good 72 had a favourable outcome Where asphyxia (hypoxicndashischaemic insult) is the cause of neonatal convulsions the outcome is poor in 50 The prognosis for neonatal convulsions when they were due to arterial or cere-brovenous infarction or intracranial haemorrhage was generally good Individually inborn errors are a very rare cause of neo-natal convulsions but in view of the treatable nature of some of these it is essential that these be considered and investigated appropriately5
Patterns of seizure activity in the newborn
Movement pattern Frequency ()
Clonic 50
tonic 20
Subtle 10ndash35 depending on maturity
myoclonic 5
Table 1
Cause incidence and outcome of neonatal convulsions in term infants14
Aetiological factor Incidence () Poor outcome ()
asphyxia 38ndash40 50
Cerebral arteriovenous
infarction
20 0
intracranial haemorrhage 12ndash20 13
Congenital cerebral anomaly 5ndash10 100
Hypoglycaemiahypocalcaemia 3ndash19
infection 3ndash20
inborn error of metabolism 1
unknown cause 10ndash13 0
Refers to moderate and severe neurodevelopmental abnormalitynumbers too small to make meaningful predictions
Table 2
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Controversies in the clinical management of neonatal seizures
In recent years we have learnt much more about the neurobi-ology of seizures and their effect on the developing brain The neonatal brain is in a neurophysiologically hyperexcitable state compared to the more mature brain and therefore is more prone to seizure activity This is due largely to a relative excess of GABA neuroreceptors GABA receptors are usually inhibitory but in the immature brain they have a paradoxically excitatory effect This changes at about term in primates and with progressive develop-ment they adopt a neuroinhibitory role6
The propensity to seizures in the neonatal brain makes resolv-ing the balance of risks between continuing seizure activity on the one hand against potentially adverse effects of therapy on the other a very important equation Added to this is the problem of accurately diagnosing neonatal seizures and whether commonly used anticonvulsants are successful in controlling them
These conundrums can be posed as a series of challenging questions which are discussed below
Do neonatal convulsions cause brain injuryConvulsions are a sign of neurological compromise and may indi-cate significant underlying structural brain damage or biochemi-cal disturbance which may cause further brain damage in its own right There has been considerable debate about the scale of the disability that convulsions cause the immature brain over and above that due to the underlying cause Most of our knowledge comes from studies in rodents and these have provided some tentative answers to this question
Seizures in the mature brain lead to neuronal necrosis but studies in very young rat pups whose brain development is somewhat similar to full-term infants have shown that a series of five brief seizures on five successive days does not cause struc-tural neuronal damage but does produce morphological changes in hippocampal neurones and worryingly deficits in the rat learning and visual spatial memory function in adolescent and adult life7 A single prolonged neonatal convulsion in similarly immature rats does not produce any functional effects8 Others have shown that following priming of the neonatal rat brain by short seizures as described above a further insult comprising induction of status epilepticus in the same rats at an older age causes neuronal necrosis9 This has been referred to as the lsquotwo hit hypothesisrsquo10
A more specific question is does seizure activity in an already significantly compromised brain cause additional neuropathol-ogy Wirrell et al11 studied a series of immature rat pups with the induction of an hypoxicndashischaemic (asphyxial) insult fol-lowed by either chemically-induced fits or a control sham pro-cedure In the more severely asphyxiated animals the degree of brain damage was increased significantly in those that had the additional burden of induced seizures
In summary these studies show that the immature brain is more resistant to short frequent post-seizure damage than the mature brain but despite resulting in no loss of neuronal numbers the function of the brain is permanently affected in later life In the asphyxiated brain seizures appear to have an additional adverse effect on brain damage Furthermore the immature brain that has been lsquoprimedrsquo by early seizures is more
paeDiatRiCS anD CHilD HealtH 184 179
vulnerable to status epilepticus later in life It would appear from these data that frequent seizures in the human infant should be stopped and this begs the question as to whether currently used anticonvulsants effectively control neonatal seizures
Can we rely on clinical versus EEG diagnosis of neonatal convulsionsTraditionally the diagnosis of neonatal convulsions has been made by observation and description of the frequency of abnor-mal movements EEG has been technically difficult in the hostile electrical activity of a neonatal intensive care environment and considerable expertise is required for analysis of the trace It is usually not practical to undertake traditional EEG recordings at the time the baby shows abnormal movements More recently various technological developments have allowed more direct investigation of neuronal electrical activity by either video-EEG or compressed recording of the amplitude integrated EEG (aEEG or CFM)
Rennie et al3 at Kingrsquos College Hospital London have under-taken extensive evaluation of video-EEG and have found that this technique detects many convulsions not recognized by a single channel aEEG or CFM trace Of 19 infants with evidence of convulsions on EEG only four were recognized on CFM but this may have been due to the observersrsquo lack of experi-ence with this technique In other centres that have developed appropriate expertise aEEG or CFM has proved more sensitive to the detection of seizures Video-EEG studies have also shown that many movements interpreted by experienced clinicians to be seizures are not associated with abnormal cortical activity Conversely many electrical seizures are not associated with abnormal movements This is referred to as electroconvulsive dissociation
In summary clinical observation alone to detect the fitting baby is unreliable in that it may either over-detect seizure activ-ity which is not present on EEG or under-detect clinical seizures in infants with EEG-proven convulsions The decision as to which babies to treat with antiepileptic drugs therefore becomes somewhat arbitrary
Do anticonvulsants stop neonatal seizuresAlthough neonatal seizures are common there are few random-ized controlled trials assessing the benefits of antiepileptic drugs (AEDs) in the treatment of this condition Phenobarbitone is the most widely used first-line AED and in an Australasian study 95 of neonatologists and paediatric neurologists used this drug as first-line management12 The most commonly used loading dosage is 20 mgkg but regimens of up to 40 mgkg have been recommended (Table 3)13 Four trials have evaluated the effect of phenobarbitone in abolishing neonatal seizures Two of these studies used EEG to monitor response to the drug1415 and one compared phenobarbitone with phenytoin15 In the latter study seizures were completely controlled in only 43 of babies and in the group where phenytoin was the first drug used com-plete seizure control was achieved in 45 This study switched babies from their first AED to the other if complete control was not obtained on EEG monitoring after exposure to first-line therapy In babies who had been given phenobarbitone as first-line therapy seizure control was only achieved in 57 after phenytoin was added In those given phenytoin first complete
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Dosage regimens for first- second- and third-line anticonvulsants in the neonatal period
Loading dose Second loading dose if first
unsuccessfulMaintenance dose
phenobarbitone 20 mgkg by slow iv injection 10 mgkg iv 25ndash5 mgkg od
phenytoin 20 mgkg iv over 20 min not recommended
midazolam 150ndash200 μgkg iv infusion 1 μgkgmin iv infusion increasing to 5 μgkgmin
until favourable response
lidocaine 2 mgkg iv over 10 min 6 mgkgh for 6 h iv then 4 mgkgh for 12 h then
2 mgkgh for 12 h
lorazepam 005ndash01 mgkg by slow iv injection
Diazepam 03ndash04 mgkg iv over 3ndash5 min
lidocaine should not be used if the infant has previously been treated with phenytoin
Table 3
seizure control was achieved with the adding of phenobarbitone in 62
Boylan et al14 assessed the efficacy of phenobarbitone (20ndash40 mgkg iv over 20 min) in 14 babies monitored by video-EEG in only four was there complete abolition of seizures and in the other 10 electroconvulsive seizure activity increased whereas clinical evidence of seizures reduced This has been termed elec-troclinical dissociation and anticonvulsant drug use in the new-born appears to increase this feature They also showed that the babies least likely to respond to the first-line AED are those with the most abnormal background EEG
Two studies have evaluated the use of phenobarbitone in babies who had sustained significant asphyxial insult at birth Hall et al13 compared high-dose phenobarbitone (mean 39 mgkg) versus standard dose (27 mgkg) and reported fewer convul-sions and a significant reduction of severe disability or death in the high dose group (RR 030 CI 010ndash093) A recent study from India16 of babies with hypoxicndashischaemic encephalopathy ran-domized 25 babies to phenobarbitone (20 mgkg loading dose) and compared them with 20 control babies Only 2 of 25 (4) in the phenobarbitone group developed convulsions compared with 8 of 20 (40) in the control group (p = 001) Because of the specific enrolment criteria (asphyxial insult) neither of these studies is strictly comparable to the studies by Painter et al15 and Boylan et al14 whose intention was to assess the efficacy of first-line anticonvulsant therapy on convulsions of any cause diagnosed either clinically or by EEG
Other anticonvulsants used as second- and third-line drugs have been subject to few studies in the newborn Midazolam is administered as a bolus followed by continuous infusion A recent study17 has shown that in 10 of 13 neonates given intravenous midazolam for status epilepticus control of electri-cal seizures was achieved within the first hour of treatment having been previously shown to be refractory to phenobarbi-tone treatment Some of these babies required a second bolus infusion of midazolam to obtain control of all electrographic seizures
In some parts of Europe lidocaine is used as a third-line anti-convulsant Malingre et al18 evaluated 20 infants refractory to
paeDiatRiCS anD CHilD HealtH 184 180
both phenobarbitone and midazolam and who were then given lidocaine by continuous infusion Lidocaine was effective in abolishing electroconvulsive seizures diagnosed by aEEG in 76 of the treatment courses studied No babies developed cardiac arrhythmias a previously reported complication of lidocaine in older patients As a result of pharmacokinetic studies the dosage regimen has been modified (see Table 3)
In summary phenobarbitone is effective in seizure control in less than 50 of babies and even when combined with phe-nytoin the efficacy of these drugs together remains poor More worrying is the observation that phenobarbitone tends to reduce clinically evident seizures thereby giving the clinician a false sense of security whilst having little or no effect on the num-bers of electroconvulsive disorders This has been summarized appropriately as lsquoafter all these years we still love what doesnrsquot workrsquo19 Both midazolam and lidocaine infusions appear to be effective in abolishing severe seizures in some infants resistant to phenobarbitone Lidocaine should not be given to babies previ-ously exposed to phenytoin for fear of a synergistic adverse effect on cardiac rhythm
Do antiepileptic drugs cause brain damageA riskndashbenefit analysis is needed to evaluate the efficacy of anticonvulsants in stopping neonatal seizures which is poor with standard anticonvulsants as discussed above against the risk of administering the anticonvulsant drugs themselves Phenobarbitone has been reported to have adverse effects on the developing brain including inhibition of brain growth20 neuronal toxicity21 and adverse behavioural and cognitive effects into adult life when administered to young animals22 Phenytoin shows unpredictable plasma levels and potential cardiotoxicity
Recent studies have shown an effect of AED exposure on the developing brain by causing neurodegeneration23 Phenytoin administration to immature rat pups at doses which produce serum levels similar to those achieved in human neonates was associated with widespread neuronal death as a result of apop-tosis (programmed cell death) Phenobarbitone had a similar effect when a dosage regimen similar to 40 mgkg was used and
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
this effect was maximal in the more immature brain Diazepam and clonazepam also resulted in a similar effect Midazolam and lidocaine were not tested in this study The combination of phenobarbitone or phenytoin with diazepam had a particularly profound effect on neurodegeneration
In summary recent data suggest that the commonly used AEDs for neonatal convulsions may in themselves cause neuro-degeneration due to apoptosis with lasting effects on develop-ment Many babies with neonatal convulsions are treated with at least two AEDs and this may produce more severe adverse effects than the seizures themselves
Practical management of neonatal seizures
Assimilation of these data and formulation of a rational policy is difficult when faced with a fitting neonate on an intensive care unit and pressure on the medical staff to lsquodo somethingrsquo but it is important to accept that sometimes doing nothing is preferable to using potentially dangerous drugs in a situation which does not warrant such intervention Many babies who have normal interseizure neurological clinical findings and whose seizures are relatively brief and infrequent probably do not need anticon-vulsant medication A normal or near-normal background EEG trace should reassure the clinician that anticonvulsants can be withheld
Some causes of neonatal convulsions are treatable such as meningitis hypoglycaemia hypocalcaemia and inborn errors of metabolism and each baby should be rapidly and carefully investigated for cause of the convulsions
In some babies clinical assessment of seizures is difficult ie when the baby is very sick small or paralyzed Sometimes it may be difficult to assess the significance of certain movement pat-terns Under these circumstances an EEG may prove to be very helpful In many units EEG is not available out of hours and a simple aEEG or CFM is strongly advised Modern instruments are very simple to apply and prolonged or frequent seizures should be identified with only moderate training The printout can be faxed to a more senior doctor if there is doubt as to what is shown on the trace
The balance of knowledge now is that frequent seizures cause additional damage to the developing brain and that treatment to abolish the seizures is warranted Unfortunately there is little evidence that the majority of seizures can be effectively termi-nated by current standard therapy Furthermore it appears that the more abnormal the background EEG the more difficult it is to control the seizures Nevertheless a written protocol for the management of neonatal convulsions is required on each unit Phenobarbitone and phenytoin remain the mainstay of treat-ment although their effectiveness is disappointing There is little to suggest that midazolam is more effective than lidocaine as third-line therapy but lidocaine is precluded if phenytoin has been previously used
In view of the anxiety as to the neurodegenerative effects on the immature brain of most anticonvulsants used in the neonatal period (particularly when multiple drugs are used) it is prefer-able to use only one drug to maximum dosage before introduc-ing a second In addition the duration of anticonvulsants should be minimized and the drugs stopped at the earliest opportu-nity It is my practice to stop anticonvulsants prior to discharge
paeDiatRiCS anD CHilD HealtH 184 18
from hospital if the baby is neurologically normal on clinical examination
REFEREnCES
1 Ronen gm penney S andrews W the epidemiology of clinical
neonatal seizures in newfoundland a population-based study
J Pediatr 1999 134 71ndash75
2 lanska mJ lanska DJ Baumann RJ et al a population-based study
of neonatal seizures in Fayette County Kentucky Neurology 1995
45 724ndash732
3 Rennie Jm Chorley g Boylan gB et al non-expert use of the
cerebral function monitor for neonatal seizure detection Arch Dis
Child Fetal Neonatal Ed 2004 89 F37ndashF40
4 tekgul H gauvreau K Soul J et al the current etoliologic profile
and neurodevelopmental outcome of seizures in term newborn
infants Pediatrics 2006 117 1270ndash1280
5 Surtees R Wolf n treatable neonatal epilepsy Arch Dis Child 2007
92 659ndash661
6 Ben-ari y Holmes gl effects of seizures on developmental
processes in the immature brain Lancet Neurol 2006 5 1055ndash
1063
7 Holmes gl gairsa Jl Chevassus-au-louis n et al Consequences of
neonatal seizures in the rat morphological and behavioral effects
Ann Neurol 1998 44 845ndash857
8 Stafstrom Ce Chronopoulos a thurber S et al age-dependent
cognitive and behavioural deficits following kainic-acid inducing
seizures Epilepsia 1993 34 420ndash432
9 Schmid R tandon p Stafstrom Ce et al effects of neonatal seizures
on subsequent seizure-induced brain injury Neurology 1999 53
1754ndash1761
10 Hoffmann aF Zhao Q Holmes gl Cognitive impairment following
status epilepticus and recurrent seizures during early development
support for the ldquotwo-hit hypothesisrdquo Epilepsy Behav 2004 5
873ndash877
11 Wirrell eC armstrong ea osman lD et al prolonged seizures
exacerbate perinatal hypoxic-ischemic brain damage Pediatr Res
2001 50 445ndash454
12 Carmo KB Barr p Drug treatment of neonatal seizures by
neonatologists and paediatric neurologists J Paediatr Child Health
2005 41 313ndash316
13 Hall Rt Hall FK Daily DK High-dose phenobarbital therapy in term
newborn infants with severe perinatal asphyxia a randomized
prospective study with three-year follow-up J Pediatr 1998 132
345ndash348
14 Boylan gB Rennie Jm pressler Rm et al phenobarbitone neonatal
seizures and video-eeg Arch Dis Child Fetal Neonatal Ed 2002 86
F165ndash170
15 painter mJ Scher mS Stein aD et al phenobarbital compared with
phenytoin for the treatment of neonatal seizures N Engl J Med
1999 341 485ndash489
16 Singh D Kumar p narang a a randomized controlled trial of
phenobarbital in neonates with hypoxic ischemic encephalopathy
J Matern Fetal Neonatal Med 2005 18 391ndash395
17 Castro Conde JR Borges H Domenech martinez e et al midazolam
in neonatal seizures with no response to phenobarbital Neurology
2005 64 876ndash879
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
18 malingre mm Van Rooij lgm Rademaker Cma et al Development
of an optimal lidocaine infusion strategy for neonatal seizures Eur
J Pediatr 2006 165 598ndash604
19 Sankar R painter mJ neonatal seizures after all these years we still
love what doesnrsquot work Neurology 2005 64 776ndash777
20 Diaz J Schain J Bailey Bg phenobarbital-induced brain growth
retardation in artificially reared rat pups Biol Neonate 1977 32 77ndash82
21 mattson RH phenobarbital toxicity in levy RH Dreifuss Fe
mattson RH et al eds antiepipeptic Drugs 3rd edn new york
Raven 1985 p 341ndash355
22 mikati ma Holmes gl Chronopoulos a et al phenobarbital
modifies seizure-related brain injury in the developing brain Ann
Neurol 1994 36 425ndash453
23 Bittigau p Sifringer m genz K et al antiepileptic drugs and
apoptotic neurodegeneration in the developing brain Proc Natl
Acad Sci U S A 2002 99 15089ndash15094
paeDiatRiCS anD CHilD HealtH 184 182
Practice points
bull the clinician needs to be aware that almost any repetitive
stereotype movement pattern can be a manifestation of
neonatal seizures
bull eeg is important in defining neonatal seizures
bull Frequent short-lived seizures have been shown to cause long-
term neurodevelopmental problems
bull Conventional anticonvulsant medication is ineffective in
abolishing neonatal seizures in greater than 50 of cases
bull there is evidence that exposure of the neonatal brain to
multiple anticonvulsants causes neuronal death
bull Future research is needed to evaluate more effective
anticonvulsants for treating this condition
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
Emotional support for families of sick neonatesMarina nicolaou
cristine Glazebrook
AbstractParents of sick neonates experience high levels of stress anxiety and
depression Most interventions with families of sick infants have focused
on fostering the motherndashinfant relationship through the provision of
information about infant developmental needs or through increased
motherndashinfant contact Many of these studies have reported improved
maternal well-being though there are some concerns about the scope
and practicality of large-scale interventions The few studies to have
prioritized emotional support for parents of sick neonates have pro-
duced encouraging results even interventions requiring relatively few re-
sources such as telephone support parent-to-parent support and group
support have been associated with reduced psychological morbidity for
parents The needs of parents can change throughout their infantrsquos hos-
pitalization and not all want or benefit from the provision of additional
support Thus neonatal intensive care units should aim to provide a
varied flexible and sustainable programme of support options Further
research should focus on the needs of fathers
Keywords mental health neonatal intensive care parents
The admission of an infant to neonatal care is acknowledged to be a source of considerable distress for families This review aims to explore evidence for the psychological impact on families of having an infant in neonatal intensive care and to identify evi-dence for the effectiveness of interventions to promote parental well-being It will conclude with recommendations for strategies to support parents of vulnerable infants and suggestions for fur-ther research
Psychological impact of neonatal care for parents
The majority of research examining the effect on parents of having a sick neonate has focused on families of premature or low birthweight infants Such research has found that parents with a sick neonate exhibit high levels of stress compared to normative samples and to parents of healthy full-term infants1 Singer et al2 examined the stress experienced by mothers of high-risk very low birthweight (VLBW) low-risk VLBW and term
Marina Nicolaou MPhil is a Teaching Assistant at the School of
Community Health Sciences University of Nottingham Nottingham UK
Cristine Glazebrook PhD is a Professor of Health Psychology at the School
of Community Health Sciences University of Nottingham Nottingham UK
PaeDiaTrics anD cHilD HealTH 184 196
infants Several self-report measures were used including the Brief Symptom Inventory the Parenting Stress Index (PSI) the Impact on Family Scale and the Family Inventory of Life Events and Changes (FILE) Mothers of VLBW infants had more psycho-logical distress at 1 month compared to mothers of term infants Mothers of high-risk VLBW infants also reported high psycho-logical distress at 2 years and high levels of parenting stress at 3 years Mothers have also been found to have higher stress levels compared to fathers Shaw et al3 examined the prevalence of acute stress disorder (ASD) in 40 parents whose infants were in the neonatal intensive care unit (NICU) Nearly half of the moth-ers (44) met the criteria for ASD although none of the fathers did Furthermore the severity of the symptoms (measured by the number of concurrent symptoms) was greater for the moth-ers than for the fathers3 The reasons behind this difference have been widely speculated with some believing that it is due to the mothersrsquo greater psychological involvement with the infant as evidenced by their general greater vulnerability to postpartum psychological disorder It could also reflect gender differences in coping style
Having an infant who requires intensive medical care repre-sents a significant emotional burden for families Not only is there extreme anxiety surrounding the infantrsquos health and distress for the childrsquos suffering there is also the unfamiliar and intimidating environment of the NICU to adjust to Hopper in her review of the literature identified sources of stress for parents of sick neo-nates as falling into three areas4 Situational factors included the severity of the infantrsquos illness and how parents adapted to the life crisis of having a sick infant Personal factors involved parental emotions about their roles and the instrumental and informa-tional support which were available to them The third area was classified as environmental sources of stress and included the environment of the NICU and the relationship between parents and members of staff This relationship has been examined by several studies in the nursing literature nurses are seen as ide-ally placed to provide the necessary support and information to parents with sick neonates However whilst some studies have shown that supportive and helpful hospital staff can have a posi-tive effect on parents other studies have highlighted the prob-lems and difficulties which can manifest It has been shown that parents and nurses often have very different ideas about issues eg the necessary skills and competencies needed in an NICU or the characteristics that make a lsquogood motherrsquo
Research has shown that there may be a relationship between high levels of parental stress and an increased likelihood of depression5 Postpartum depression is a psychiatric illness which appears in 10ndash15 of postpartum women Its reported preva-lence rates however have ranged from less than 10 up to 306 depending on the instruments used the population exam-ined and the timing of the research Several factors have been found to be associated with postpartum depression including poor social support and infant-related stressors6 Evidence indi-cates that postnatal depression may be underreported and this is of concern since the mental and psychological health of the mother can affect her relationship with her infant and thus the infantrsquos cognitive and emotional development5 Depressed moth-ers appear to look touch and talk to their infants less frequently and also appear to show fewer positive and more negative faces7 The vocalizations of mothers suffering with depression have also
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
been found to be less effective at promoting cognitive growth and learning in infants8
If researchers are interested in finding ways of providing sup-port for families of sick neonates then they must listen to what such families perceive their needs to be in order to avoid increas-ing anxiety and distress Furthermore the provision of appropri-ate support be it emotional informational or social will enhance parental coping abilities increase self-esteem and reduce anxiety It should be noted though that the research conducted around these issues has often taken lsquosupport needsrsquo as being synony-mous with lsquoinformation needsrsquo Such studies have examined the type the amount and quality of information that parents receive and perceive themselves as needing but have not explored in equal depth the perceived emotional support needs of families who have a sick infant In addition the needs of parents may change throughout their infantrsquos illness Ward examined the per-ceived needs of 52 parents of infants in an NICU9 Parents rated the needs of their hospitalized infant as most important along with the need to be reassured Interestingly they ranked their support needs as least important This research was conducted during the first week of the infantsrsquo hospitalization however which would explain the preoccupation of the parents with the infantrsquos health These results demonstrate that if researchers want to find ways of providing emotional support to parents of sick neonates they must be prepared not only to listen to parents but also to be flexible enough to satisfy the parentsrsquo changing needs and expectations
Interventions aimed at supporting parents
Most interventions that been evaluated in controlled studies have focused on supporting the motherndashinfant relationship and provid-ing information on infant development Many of these interven-tions have included the aim of improving the parental emotional state and thus psychological outcomes such as stress or anxi-ety have been assessed However few studies appear to include fathers This means that strategies implemented to provide emo-tional support to families of sick neonates are often derived from interventions tailored for mothers even though fathers may have different emotional needs
A wide range of interventions with mothers and infants has been evaluated in the NICU Increasing motherndashinfant contact through kangaroo care has been found to reduce maternal anxiety1011 and educational programmes delivered to fami-lies in the NICU have also been associated with reduced emo-tional difficulties in parents12ndash14 Kaaresen and colleagues implemented an intervention which consisted of eight sessions before discharge and four home visits all by trained nurses The sample included 71 premature infants in the intervention group 69 premature infants in the control group and 74 infants in the full-term control group The randomized controlled trial found that the intervention reduced parenting stress in both mothers and fathers of premature infants compared to controls to a level equivalent to parents in the term control group13 At 6 months corrected age mothers of preterm infants who had not received the intervention had total PSI scores which were 17 points higher than the mothers of infants born at term (an effect size of 057) A similar study evaluated the efficacy of an educationalndashbehavioural programmendashCreating Opportunities for
PaeDiaTrics anD cHilD HealTH 184 19
Parent Empowerment (COPE) ndash through a randomized controlled trial with 260 families of premature infants14 COPE was a four-phase educationalndashbehavioural programme which began as early as 2ndash4 d after mothers had given birth and continued until 1 week after discharge from the NICU The programme consisted of audiotaped and written infant behaviour information along with photographs which focused on common behaviours and characteristics of premature infants It also included various par-ent activities in the form of a four-phase workbook which aimed to assist mothers in the implementation of the experimental infor-mation COPE was found significantly to reduce maternal stress in the NICU as well as maternal anxiety and depressive symptoms after hospitalization In contrast a cluster randomized trial of a parenting intervention delivered to mothers of very premature infants from soon after birth showed no benefits for parenting stress1 The authors hypothesized that the intervention had not been of sufficient intensity particularly in the weeks surrounding discharge Neonatal care presents a significant barrier to parent-ing in the early weeks following a very preterm birth and so inter-ventions which focus on the developmental needs of infants and the parentndashchild relationship should particularly aim to support parents as they take on the parenting role There was also concern that the intervention had failed to reach those most at risk
Since large-scale projects can be costly to implement and may often fail to reach the families in most need it may be wiser to focus on intervention programmes which are more practical and easier to implement within a neonatal care setting Research has shown that even interventions which are based on one-off meet-ings with parents of sick neonates can be effective Jotzo and Poets examined the effect of an intervention programme aimed at reducing the severity of traumatic responses as a result of giv-ing birth prematurely15 Their programme consisted of a one-off intervention meeting along with additional psychological help throughout the hospitalization of the infant The meeting cov-ered a variety of issues including a reconstruction of the events shortly before and after the infantrsquos birth relaxation techniques discussion of coping strategies available resources and social support and support during emotional outbursts The measures used included the Impact of Event Scale (IES) and the Peritrau-matic Dissociative Experience Questionnaire At discharge the mothers who received the intervention were found to have a significantly lower traumatic impact as a result of premature birth Furthermore fewer mothers in the intervention group showed symptoms of clinically significant psychological trauma at discharge compared to mothers in the control group (36 vs 76)15 The lsquoParents Circle Programrsquo is another intervention with a similar structure16 This consisted of a 90 min session for parents with the aim of enhancing the developing relationship between parents and infants and to offer parents support A total of 104 parents (59 mothers and 45 fathers) and 44 members of hospital staff were asked to evaluate the programme and their results were analysed using content analysis Families reported gaining perspective on their situation feeling supported becom-ing aware of cues and optimizing interactions and becoming aware of available resources Parents and staff alike felt that participating in the intervention helped parents overcome the difficulties associated with the early time of their infantrsquos hos-pitalization Additional studies have also found positive results with fairly minimal interventions including discussion groups
7 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
in the NICU music during kangaroo care and pairing mothers of sick neonates with trained mothers who had been through similar experiences
Parent support programmes
Parent support programmes (PSPs) which are based in NICUs can provide parents with the opportunity to talk to parents who have been in similar situations and also to discuss their emo-tions with professionals who can help them cope with their situa-tion111718 The parent-to-parent support programme for mothers of preterm infants evaluated by Preyde and Ardal included edu-cational parental support group meetings and individual par-ent-to-parent support (primarily telephone support)19 Measures used included the Parental Stressor Scale NICU the State and the Trait Anxiety Inventories and the Beck Depression Inven-tory After 4 months of participation mothers in the intervention group reported lower levels of stress state anxiety and depres-sion compared to control group mothers The authors speculated however that the participants who were able to meet face to face with other parents were those who benefited the most Hurst conducted a comprehensive survey of an NICU-based PSP This PSP was provided in a variety of formats including a weekly parent support group hospital visitation and 24-h telephone sup-port20 Of the 477 participants 303 families used the PSP dur-ing a 2-year evaluation period with 78 using only one form of support and 18 using two forms Of a sub-sample of 48 parents asked to complete an evaluation of the PSP 92 stated that they would recommend such a programme to other parents Furthermore the majority of parents felt that it made them feel supported and helped them deal with their emotions20 This is an indication that such programmes can be very successful in sup-porting parents throughout their infantrsquos hospitalization It also shows that it can be beneficial to give parents several options and formats when it comes to such support services It is impor-tant to consider though that both the Hurst and the Preyde and Ardal studies found that some participants did not find the sup-port programmes helpful even reporting that they had caused them increased stress and anxiety Therefore it should not be assumed that support programmes will suit every individual and will provide the required support for all parents1920 NICUs need to be flexible enough to provide parents with a range of forms of support to choose from
The increased understanding of the strains that parents of sick neonates have to deal with has also led to efforts to improve customary practices in NICUs Family-centred care focuses on infants and their needs and attempts to redefine the relationship between parents and caregivers These practices strive to provide parents with support during their infantrsquos illness by focusing on freely sharing information and on the collaboration between parents and hospital staff Family-centred care has been found to be associated with several beneficial outcomes including improved parental satisfaction increased parental comfort staff satisfaction and decreased parental stress18 Research is already examining these practices and questioning how these can be improved further Such research reflects the increasing effort focused on lsquohumanizingrsquo the environment in NICUs in order to make parents feel more comfortable about spending time with their infants
PaeDiaTrics anD cHilD HealTH 184 19
Conclusion
Surprisingly few interventions have prioritized the provision of emotional support for parents of sick neonates or accounted for the changing needs and wishes of parents over the course of their infantrsquos care Large-scale supportive education-based inter-ventions have been shown to be effective in reducing parental distress However the feasibility and sustainability of such pro-grammes should also be considered Programmes which require significant additional resources can be expensive and there are also issues of training and quality control Interventions which require significant input from parents may also place additional burdens on families making them potentially less accessible to those most at risk Arguably the aim should be to explore ways of providing acceptable and effective informational support which could be complemented by emotional support from health professionals and from other parents in the unit Increasingly studies are exploring the use of computers and multimedia as an engaging flexible and cost-effective method of targeting indi-vidual needs and providing support and information Such com-puter-based and interactive multimedia interventions have been found to be successful with a range of patient groups and could therefore be examined as a complementary method of providing informational support to families with sick neonates
REfEREnCEs
1 Glazebrook c Marlow n israel c et al randomised trial of a
parenting intervention during neonatal intensive care Arch Dis Child
Fetal Neonatal Ed 2007 92 F438ndash443
2 singer lT salvator a Guo s collin M lilien l Baley J Maternal
psychological distress and parenting stress after the birth of a very
low-birth-weight infant JAMA 1999 281 799ndash805
3 shaw rJ Deblois T ikuta l Ginzburg K Fleisher B Koopman c
acute stress disorder among parents of infants in the neonatal
intensive care nursery Psychosomatics 2006 47 206ndash212
4 Hopper a sources of stress for parents of a sick neonate a
literature review Pediatr Nurs 2000 30 29ndash32
5 Davis l edwards H Mohay H wollin J The impact of very
premature birth on the psychological health of mothers Early Hum
Dev 2003 73 61ndash70
6 Bernazzani O saucier J-F David H Borgeat F Psychosocial
predictors of depressive symptomatology level in postpartum
women J Affect Disord 1997 46 39ndash49
7 Field T infants of depressed mothers Infant Behav Dev 1995 18
1ndash13
8 Kaplan Ps Bachorowski J-a Zarlengo-strouse P child-directed
speech produced by mothers with symptoms of depression fails
to promote associative learning in 4-month-old infants Child Dev
1999 70 560ndash570
9 ward K Perceived needs of parents of critically ill infants in
a neonatal intensive care unit (nicU) Pediatr Nurs 2001 27
281ndash286
10 lai Hl chen cJ Peng Tc et al randomized controlled trial of music
during kangaroo care on maternal state anxiety and preterm infantsrsquo
responses Int J Nurs Stud 2006 43 139ndash146
8 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
11 Tallandini Ma scalembra c Kangaroo mother care and mother-
premature infant dyadic interaction Infant Ment Health J 2006 27
251ndash275
12 Ohgi s Fukuda M akiyama T Gima H effect of an early intervention
programme on low birthweight infants with cerebral injuries
J Paediatr Child Health 2004 40 689ndash695
13 Kaaresen Pi ronning Ja Ulvund se Dahl lB a randomized
controlled trial of the effectiveness of an early-intervention program
in reducing parenting stress after preterm birth Pediatrics 2006
118 e9ndash19
14 Melnyk BM Feinstein nF alpert-Gillis l et al reducing premature
infantsrsquo length of stay and improving parentsrsquo mental health
outcomes with the creating opportunities for parent empowerment
(cOPe) neonatal intensive care unit program a randomized
controlled trial Pediatrics 2006 118 e1414ndash1427
15 Jotzo M Poets cF Helping parents cope with the trauma of
premature birth an evaluation of a trauma-preventive psychological
intervention Pediatrics 2005 115 915ndash919
16 Pearson J andersen K evaluation of a program to promote positive
parenting in the neonatal intensive care unit Neonatal Netw 2001
20 43ndash48
17 roman l lindsay J Boger r et al Parent-to-parent support
initiated in the neonatal intensive care unit Res Nurs Health 1995
18 385ndash394
18 Meyer ec coll cTG lester BM Boukydis cFZ McDonough sM Oh w
Family-based intervention improves maternal psychological well-
being and feeding interaction of preterm infants Pediatrics 1994
93 241ndash246
PaeDiaTrics anD cHilD HealTH 184 19
19 Preyde M ardal F effectiveness of a parent ldquobuddyrdquo program for
mothers of very preterm infants in a neonatal intensive care unit
CMAJ 2003 168 969ndash973
20 Hurst i One size does not fit all Parentsrsquo evaluations of a support
program in a newborn intensive care nursery J Perinat Neonatal
Nurs 2006 20 252ndash261
Practice points
bull Parents of sick neonates experience significant distress and
exhibit higher levels of stress anxiety and depression than
parents of healthy infants
bull educational support emotional support and increased
motherndashinfant contact have been shown to promote maternal
well-being
bull emotional support for fathers has been largely neglected in
the research literature
bull Parents benefit from a choice of supportive facilities which
could include face-to-face sessions with health professionals
telephone support hospital visitation parent-to-parent
support and unit-based group support meetings
bull Parentsrsquo support needs can change during their infantrsquos
hospitalization and not all parents want or benefit from the
provision of additional information and emotional support in
the neonatal unit
9 copy 2008 elsevier ltd all rights reserved
Personal Practice
When should enteral feeds be started in preterm infantsnicholas D embleton
AbstractPaediatricians are regularly faced with the question of when best to start
enteral feeds in preterm infants this is important as longer term out-
come may be compromised by sub-optimal nutrition in early life clinical
factors that may affect the decision to start and the risk and benefits
are discussed
Keywords breast milk feeding nutrition parenteral nutrition
Key points in the history
Alice is lsquonutritionally vulnerablersquo and whilst this may not be immediately apparent it will affect her long term outcome Her energy stores are extremely limited and consist primarily of pro-tein She has less than 5 fat and little energy associated with stored glycogen She is losing about 1 gkgd protein equivalent so she needs at least that and a minimum of 50ndash60 kcalkg of energy just to maintain the status quo let alone grow
Her weight is on the 25th centile Review of any antenatal his-tory may reveal whether fetal growth was normal Fetal growth retardation can occur with a weight greater than 10th centile The presence of antenatal absent or reversed end diastolic flow in the umbilical artery indicates poor gut blood flow This increases the risk of necrotizing enterocolitis (NEC) and might suggest a more cautious approach to starting feeds1
She has no important cardiovascular problems but if she were hypotensive gut blood flow may be low There is no umbilical
Nicholas D Embleton BSC (Hons) MBBS (Hons) MD FRCPCH is Consultant in
Neonatal Medicine at Newcastle Neonatal Service Royal Victoria
Infirmary Newcastle upon Tyne NE1 4LP UK
Should you start feeds at a day of age
alice was born following spontaneous labour at 30 weeksrsquo
gestation she weighed 1300 g and is now 18 h old she was
briefly ventilated and then extubated to continuous positive
airway pressure 12 h ago in 35 oxygen she has had caffeine
citrate but still has intermittent episodes of self-correcting
apnoea she was commenced on iv 10 dextrose but this was
replaced by a parenteral amino acid solution (referred to as
lsquotPnrsquo) along with intralipid at 0900 this morning serum glucose
is 11 mmoll and blood pressure is 42 systolic
PaeDiatrics anD cHilD HealtH 184 20
arterial catheter in situ but there is no good evidence that this should delay the decision to start feeds Her glucose is high but this is quite common in a baby like this Could this be a sign of sepsis Caffeine does not affect the incidence of NEC2 The great-est risk factor for NEC in this case is prematurity
What else might be found on examination
Up until 24 h ago she was swallowing large amounts of amniotic fluid What will have changed since then
General examination should confirm peripheral perfusion lsquogestaltrsquo view (does she look lsquowellrsquo) and cardiovascular status lsquoBowel soundsrsquo are not usually helpful
The most important variable likely to affect gut perfusion is the arterial duct Precordial lsquoheaversquo and a loud murmur are sug-gestive but it is possible to have a significant ductal shunt in a baby with a normal examination Cardiac ultrasound will con-firm this diagnosis It might be better to treat a large shunt first with indometacin and to delay starting feeds for a further 24 h
It is not possible to assess gut perfusion clinically but normal perfusion elsewhere (adequate urine output usually indicates adequate renal perfusion) would be reassuring Most preterm babies have a few abdominal lsquoloopsrsquo visible but a distended abdomen with many palpable loops suggests ileus This might be secondary to sepsis or poor gut blood flow Preterm babies do not pass much meconium in the first 24ndash48 h
Balance of risks between starting and withholding feeds
Alice requires 35ndash4 gkgd of protein and 120 kcalkgd to grow3 This will initially be provided parenterally Delaying feeds increases the risk of gut villous atrophy and prolongs the need for lsquototal parenteral nutrition (TPN)rsquo TPN requires intravenous access and so increases the risk of sepsis and when prolonged use is required combined with the lack of enteral feeding may result in hepatic impairment
Delaying feeds may allow a gut that has been chronically under-perfused to re-establish more normal perfusion although normal gut endocrine function digestive enzyme upregulation and motility require a source of intraluminal nutrients1 A recent study suggested benefit from delaying the introduction of feeds4 but methodologi-cal problems exist5 Although a Cochrane meta-analysis suggested no benefit only two studies were included6 A large UK-based trial is examining the effect of early or late feeding in preterm infants who were born growth retarded following identification of antena-tal absent or reversed end diastolic flow in the umbilical artery7
When starting feeds what volume should be used
There are no good data to guide this decision We start with 24 mlkg (1 mlkgh) and then increase by this amount each day Most babies achieve full enteral feeds (ge150 mlkgd) by a week of age Feeding guidelines improve the outcome8 Measure-ment or assessment of gastric aspirates is not consistently useful in predicting subsequent feeding intolerance or development of NEC Aspirate volumes equivalent to or sometimes greater than the amount given in the preceding 1ndash2 h are usually normal Most aspirates have a greenish colour Thick bloody or intensely bile-stained aspirates require detailed assessment
0 copy 2008 elsevier ltd all rights reserved
Personal Practice
What else affects decisions and outcome
Feeding success is affected by sepsis and NEC Scrupulous atten-tion should be paid to hand washing and intravenous access and blood sampling should be minimized There is no good evidence to support the routine use of pro-kinetic agents or H2 blockers
The most important clinical intervention affecting the occur-rence of NEC is the use of breast milk9 All efforts should be directed at persuading parents of the benefits and supporting the process Some clinicians delay starting feeds for a further 24 h whilst expressed breast milk becomes available Donor breast milk might be equally efficacious10
RefeRenceS
1 Dorling J Kempley s leaf a Feeding growth restricted preterm
infants with abnormal antenatal Doppler results Arch Dis Child Fetal
Neonatal Ed 2005 90 F359ndash363
2 schmidt B roberts rs Davis P et al caffeine therapy for apnea of
prematurity N Engl J Med 2006 354 2112ndash2121
PaeDiatrics anD cHilD HealtH 184 20
3 embleton nD Pang n cooke rJ Postnatal malnutrition and growth
retardation an inevitable consequence of current recommendations
in preterm infants Pediatrics 2001 107 270ndash273
4 Berseth cl Bisquera Ja Paje VU Prolonging small feeding volumes
early in life decreases the incidence of necrotizing enterocolitis in
very low birth weight infants Pediatrics 2003 111 529ndash534
5 Menon G Boyle eM embleton nD et al introduction of enteral
feeds in preterm infants Pediatrics 2004 114 327ndash328
6 Kennedy Ka tyson Je chamnanvanikij s early versus delayed
initiation of progressive enteral feedings for parenterally fed low
birth weight or preterm infants Cochrane Database Syst Rev 2000
cD001970
7 wwwnpeuoxacukadept
8 Patole sK de Klerk n impact of standardised feeding regimens on
incidence of neonatal necrotising enterocolitis a systematic review
and meta-analysis of observational studies Arch Dis Child Fetal
Neonatal Ed 2005 90 F147ndash151
9 lucas a cole tJ Breast milk and neonatal necrotising enterocolitis
Lancet 1990 336 1519ndash1523
10 Boyd ca Quigley Ma Brocklehurst P Donor breast milk versus
infant formula for preterm infants systematic review and meta-
analysis Arch Dis Child Fetal Neonatal Ed 2007 92 F169ndash175
1 copy 2008 elsevier ltd all rights reserved
self-assessment
Case 1A term male infant born to consanguineous parents is assessed at 24 h of age due to poor feeding profuse yellow watery diar-rhoea and irritability He weighed 32 kg at birth and delivery was uneventful There was no polyhydramnios He has been breastfed since birth On examination he is pale with a non-tender but distended abdomen and reduced bowel sounds His weight is 275 kg and he looks dehydrated Examination is otherwise normal
Initial investigations (normal values in parentheses) showed
sodium 149 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 65 mmollitre (25ndash75)
creatinine 147 μmollitre (40ndash110)
chloride 119 mmollitre (95ndash105)
haemoglobin 172 gdl (140ndash200)
White blood cell count 80 times 109litre (100ndash260)
Platelet count 302 times 109litre (150ndash400)
arterial blood gas
ph 720 (730ndash745)
PcO2 23 kPa (46ndash60)
Bicarbonate 68 mmollitre (220ndash260)
Base excess minus186 mmollitre (minus20 to +20)
lactate 59 mmollitre (06ndash24)
An abdominal X-ray shows distended bowel loops with no intramural thickening or pneumoperitoneum (Figure 1)
He was given nil by mouth and received intravenous fluids and antibiotics His dehydration improved but the metabolic acidosis and diarrhoea persisted despite receiving no enteral feeds and the commencement of total parenteral nutrition Blood and stool cultures were negative
1 Which of the following best describes these results Choose ONE answer ONLY from the followingA Hypernatraemia hyperchloraemic metabolic acidosis
with increased anion gapB Hypernatraemia hyperchloraemic metabolic acidosis
with normal anion gap
Manish Sadarangani BM BCh MA MRCPCH is Clinical Research Fellow
at the Department of Paediatrics University of Oxford Centre for
Clinical Vaccinology and Tropical Medicine Churchill Hospital
Oxford OX3 7LJ UK
Shabna Rajapaksa MB BChir MA MRCPCH is Specialist Registrar in
Paediatrics at the Paediatric Intensive Care Unit John Radcliffe
Hospital Oxford OX3 9DU UK
Nicholas Mann MD FRCP FRCPCH DCH is Consultant Paediatrician at the
Department of Paediatrics Royal Berkshire Hospital Reading RG1
5AN UK
self-assessment
C Hypernatraemic dehydration and compensated metabolic acidosis
D Acute renal failureE Renal tubular acidosis
2 What is the likely diagnosis Choose ONE answer ONLY from the followingA Hirschsprung disease ndash long segmentB Cystic fibrosis with meconium ileusC Microvillus inclusion diseaseD Cowrsquos milk protein intoleranceE Lactose intolerance
3 What is the investigation of choice Choose ONE answer ONLY from the followingA Rectal biopsy with staining for acetylcholine receptorsB Immunoreactive trypsinC Gastrointestinal endoscopy and biopsyD Stool microscopy and cultureE Stool reducing substances
Case 2A 4-year-old boy presents with a 3 d history of jaundice and a florid rash He has had orange urine and there is no change in his stool colour His family originate from Kosovo and have lived in the UK for the last 8 years He has never left the UK There is no history of blood transfusion or sex-ual abuse The grandmother was recently diagnosed with hepatitis B
On examination he is well apyrexial and mildly jaundiced with cervical and axillary lymphadenopathy He has an exten-sive papular rash over the face extremities and trunk (Figure 2) There is 3 cm hepatomegaly with no splenomegaly or ascites Examination is otherwise normal
Figure 1 abdominal X-ray of baby
Paediatrics and child health 184 202 copy 2008 elsevier ltd all rights reserved
self-assessment
Initial investigations are as follows
haemoglobin 110 gdl (113ndash135)
White blood cell count 108 times 109litre (50ndash150)
Platelet count 278 times 109litre (150ndash400)
inr 10 (08ndash12)
aPt ratio 10 (08ndash13)
sodium 140 mmollitre (135ndash145)
Potassium 42 mmollitre (35ndash50)
Urea 56 mmollitre (25ndash75)
creatinine 65 μmollitre (45ndash120)
total bilirubin 66 μmollitre (0ndash15)
conjugated bilirubin 23 μmollitre (0ndash10)
alanine aminotransferase (alt) 2033 iUlitre (0ndash35)
alkaline phosphatase 987 iUlitre (71ndash234)
Gamma-glutamyl transferase (GGt) 870 iUlitre (0ndash51)
1 What is the name of this rash Choose ONE answer ONLY from the followingA Erythema multiformeB Erythema migransC GianottiminusCrosti syndromeD EczemaE Dermatitis herpetiformis
2 What is the most likely diagnosis Choose ONE Answer ONLY from the followingA Autoimmune hepatitisB Hepatitis BC Hepatitis DD Wilson diseaseE Alpha-1 antitrypsin deficiency
3 What is the best means of management Choose ONE answer ONLY from the followingA Isolation until the jaundice disappearsB ImmunosuppressionC Copper chelating agents and genetic counsellingD Patient and family education with consideration of
antiviral agentsE Liver transplantation
Case 3A 10-month-old boy presents with 3 weeks of vomiting and constipation ndash he is passing hard stools every 2ndash3 days He has fallen from the 9th to below the 04th centile in the last 6 weeks He passed meconium within the first 24 h of life On examina-tion he looks pale and there are some dysmorphic features ndash a short nose long philtrum and wide mouth He has normal heart sounds with a grade 3 ejection systolic murmur loudest at the upper right sternal edge Examination is otherwise normal
Initial investigations are as follows
haemoglobin 91 gdl (113ndash141)
total white blood cell count 124 times 109litre (60ndash170)
Platelet count 407 times 109litre (150ndash400)
sodium 144 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 78 mmollitre (25ndash75)
creatinine 78 μmollitre (45ndash120)
albumin 52 glitre (35ndash50)
corrected calcium 384 mmollitre (238ndash263)
Phosphate 167 mmollitre (099ndash157)
1 What is the most likely diagnosis Choose ONE answer ONLY from the followingA HyperparathyroidismB Acute leukaemiaC Williams syndromeD Hypervitaminosis DE Familial hypocalciuric hypercalcaemia
2 Which investigation would be most useful in establishing the diagnosis Choose ONE answer ONLY from the followingA Intact parathyroid hormone assayB Blood filmC Fluorescent in-situ hybridization for 7q1123 deletionD 25-hydroxyvitamin D assayE Urine calciumcreatinine ratio
3 Which of the following treatments would not be suitable for this patient Choose ONE answer ONLY from the followingA Low calcium dietB Normal saline infusionC FurosemideD CorticosteroidsE Bisphosphonates
Case 4A 10-week-old girl presents with a 2-day history of poor feed-ing Her mother has been concerned about weakness since birth She only has a flicker of movement in the arms none in the legs and has a weak cry She has been passing urine and opening her bowels normally She was born at full term by normal delivery and did not require any resuscitation at birth Normal fetal movements were felt antenatally and there was no polyhydramnios She is the first child of non- consanguineous parents and there is no significant family his-tory On examination she is alert and fixing and following appropriately She has a weak cry and a weak suck There is reduced central and peripheral tone with marked head lag
Figure 2 rash found on examination
Paediatrics and child health 184 203 copy 2008 elsevier ltd all rights reserved
self-assessment
Muscle power is grade 3 out of 5 in the arms and legs There is no muscle or tongue fasciculation and she has absent reflexes throughout The remainder of the examination is normal
Electromyogram shows irregular polyphasic motor unit potentials with marked instability consistent with a dener-vating and re-innervating process (Figure 3)
1 Which of the following additional investigations may be helpful Choose ONE answer ONLY from the followingA Nerve conduction studiesB Creatine kinase assayC Muscle biopsyD SMN1 gene analysisE All of the above
2 What is the most likely cause of this childrsquos symptoms Choose ONE answer ONLY from the followingA Congenital myotonic dystrophyB Duchenne muscular dystrophyC PraderminusWilli syndromeD Spinal muscular atrophyE Mitochondrial myopathy
3 What is the mode of inheritance of this disease Choose ONE answer ONLY from the followingA X-linked recessiveB Autosomal recessiveC Autosomal dominantD MitochondrialE Sporadic
Case 5A 13-year-old girl presents with a 3-week history of fever up to 40degC night sweats and headache She has a reduced appetite with some weight loss She has no other specific symptoms She was on holiday in China 7 months ago On examination she looks well and has a temperature of 387degC There is no lymphadenopathy and no rashes Examination is entirely normal
Results of investigations are as follows
haemoglobin 126 gdl (120ndash160)
total white blood cell count 132 times 109litre (43ndash108)
neutrophil count 115 times 109litre (25ndash75)
Platelet count 244 times 109litre (150ndash400)
Blood film neutrophilia with left shift
erythrocyte sedimentation rate 63 mmh (1ndash20)
c-reactive protein 219 mglitre (0ndash5)
Blood culture Streptococcus intermedius
from anaerobic bottle only
csf culture negative
Magnetic resonance imaging (MRI) of the brain shows acute frontal sinusitis with a large intracranial frontal extra-dural empyema (Figure 4)
1 Which of the following would be appropriate management Choose ONE answer ONLY from the followingA A 12-week course of intravenous antibioticsB Drainage of the frontal sinus followed by 2 weeks of
intravenous antibioticsC Drainage of the empyema followed by 2 weeks of
intravenous antibioticsD Drainage of the empyema and the frontal sinus
followed by 2 weeks of oral antibiotics
1151
1152
1153
1154
1155
1156
1157
1158
1159
1200
50ms 1mV
Figure 3 electromyogram recording from the patient Figure 4 Parasagittal section from mri scan of patient
Paediatrics and child health 184 204 copy 2008 elsevier ltd all rights reserved
self-assessment
E Drainage of the empyema and the frontal sinus followed by 8 weeks of intravenous antibiotics
2 Streptococcus intermedius is a potential pathogen in which of the following infections Choose ONE answer ONLY from the followingA Liver abscessB Urinary tract infectionC MeningitisD Thoracic empyemaE Pneumonia
3 Which of the following statements regarding lsquopyrexia of unknown originrsquo in children is false Choose ONE answer ONLY from the followingA Malignancy is the underlying pathology in 5ndash15 of
casesB An aetiology will be found in over 90 of casesC The most common cause is infectionD A rheumatological cause is found in 10ndash20 of casesE Familial Mediterranean fever can occur in children of
non-Mediterranean ethnicity
Answers
Case 11 AThe anion gap is a useful tool to differentiate the causes of a metabolic acidosis It is calculated by the equation
Anion gap = [Na K ] [Cl HCO ]3+ + minus minus+ minus +
It represents the effect of unmeasured anions on the plasma pH and is normally 10ndash18 mmollitre
2 CMicrovillus inclusion disease is a severe autosomal recessive enteropathy that is typically apparent within hours or days after birth It is the second most common cause of protracted diarrhoea in the newborn after infectious causes It is characterized by severe yellow watery diarrhoea and malabsorption due to hypoplasia andor atrophy of the villi of the small intestine secondary to an inherited defect in the brush border membrane This results in severe dehydration malnutrition and metabolic acidosis due to bicarbonate loss from the gut
3 CDiagnosis of microvillus inclusion disease is made on small bowel biopsy Electron microscopy findings are of intracellular brush border inclusions and densely packed apical cytoplasmic vesicular bodies indicating microvillous atrophy There is no cure Treatment is supportive with total parenteral nutrition and consideration of small bowel transplantation
Further reAding
Goulet O ruemmele f causes and management of intestinal failure
in children Gastroenterology 2006 130(suppl 1) s16ndash28
rhoads Jm Vogler rc lacey sr et al microvillus inclusion disease
In vitro jejunal electrolyte transport Gastroenterology 1991
100 811ndash817
Case 21 CGianottindashCrosti syndrome is a distinct self-limiting rash commonly associated with viral infections in children between 2 and 6 years of age It presents as multiple pink to redminusbrown papules or papulovesicles which may be pruritic and can become confluent Gianotti and Crosti initially described the exanthema as associated with hepatitis B virus and they termed it papular acrodermatitis of childhood It can occur in several viral diseases eg hepatitis A B and C coxsackie viruses and cytomegalovirus
2 BHepatitis is a syndrome characterized by inflammation or injury of liver cells which may develop into cell necrosis and subsequently fibrosis andor cirrhosis Biochemically there are raised liver enzymes The degree of transaminase elevation does not correlate with the severity of the disease process Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of viral hepatitis
3 DHepatitis B infection is transmitted via blood sexually or vertically Infection may be acute or chronic Diagnostic markers are the presence of surface antigen (HBsAg) and HBV DNA The presence of e antigen (HBeAg) indicates high infectivity Infected newborns have a 95 risk of becoming carriers this risk decreases with infection acquired later in childhood Approximately 15ndash25 of HBV carriers will die from cirrhosis or hepatocellular carcinoma Extrahepatic findings are more common in older children and include membranous glomerulonephritis and GianottiminusCrosti syndrome Fulminant hepatic failure occurs in severe cases resulting in persistent jaundice encephalopathy and coagulopathy Management includes counselling family members monitoring for ongoing liver disease and consideration of antiviral therapy
Further reAding
Brandt O abeck d Gianotti r Burgdorf W Gianotti crosti
syndrome J Am Acad Dermatol 2006 54 136ndash145
slowik mK Jhaveri r hepatitis B and c viruses in infants and
young children Semin Pediatr Infect Dis 2005 16 296ndash305
Case 31 CHypercalcaemia is uncommon in infancy The most common symptoms in this age group are irritability vomiting and constipation It may be a manifestation of Williams syndrome vitamin D or calcium excess as well as disorders associated with reduced bone formation such as hypophosphatasia or increased bone resorption such as malignancy Occasionally
Paediatrics and child health 184 205 copy 2008 elsevier ltd all rights reserved
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-
SympoSium neonatology
Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemiaJ m Hawdon
Abstractat birth the newborn baby undergoes many adaptive changes to inde-
pendent extrauterine life these include the changes of metabolic adap-
tation which must be understood in order to identify and manage the
conditions in which metabolic adaptation is delayed impaired or fails
resulting in low levels of glucose and other metabolic fuels which in turn
affect neonatal neurological function and if prolonged and severe cause
potential adverse outcome Babies identified as at risk of impaired met-
abolic adaptation must undergo clinical monitoring including accurate
blood glucose monitoring tailored to their condition Babies who present
with abnormal clinical signs in association with a low blood glucose level
must be investigated for underlying cause and treated promptly preven-
tion and treatment of clinically significant hypoglycaemia must be planned
to avoid compromising successful establishment of breast feeding
Keywords alternative fuels blood glucose breast feeding neonatal
metabolic adaptation operational thresholds risk factors
Introduction
At birth the newborn baby undergoes many adaptive changes to independent extrauterine life These include the changes of met-abolic adaptation essential to ensure energy provision to vital organs and then to sustain growth and further development The changes involved in metabolic adaptation must be understood in order to identify and manage the conditions in which metabolic adaptation is delayed impaired or fails The clinical outcome of these circumstances is usually referred to with the single short-hand diagnostic term lsquoneonatal hypoglycaemiarsquo However as will be illustrated in this article it is not appropriate to ascribe a diagnostic label to neonatal hypoglycaemia first because glucose is not the only fuel in the neonatersquos fuel economy and second because hypoglycaemia is the consequence of a number of vari-ous underlying disorders and thus does not in itself warrant a diagnostic label
There have been extensive studies of metabolic adaptation in human neonates and neonatal non-human mammals The latter studies have identified those mammals most similar to humans
J M Hawdon MA MBBS MRCP FRCPCH PhD is Consultant Neonatologist and
Honorary Senior Lecturer at UCL EGA Institute for Womenrsquos Health
Elizabeth Garrett Anderson and Obstetric Hospital University College
London Hospitals NHS Foundation Trust Huntley Street London UK
paeDiatRiCS anD CHilD HealtH 184 161
in terms of metabolic adaptation and sought to compare nutri-tionally comparable time frames eg suckling versus weaning periods Whilst the processes of metabolic adaptation are well described in term and preterm human neonates there are few if any clinical studies in human neonates of sufficient rigour to provide evidence for the circumstances in which brain injury may occur and thus it is not possible to provide evidence-based guide-lines for the prevention and management of clinically significant hypoglycaemia Therefore recommendations in this article and in the referenced review articles by recognized experts remain pragmatic and urge clinicians to individualize management for each baby placing heavy emphasis on careful clinical evaluation rather than single numerical definitions of brain-injuring hypogly-caemia and on detecting and treating underlying pathologies1ndash6
Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
During intrauterine life the fetus receives via the placenta a con-stant supply of nutrients initially for growth but in the third tri-mester also for storage Glucose crosses the healthy placenta at a rate of approximately 5 mgkgmin In addition to that required for basal fetal metabolism glucose is converted to glycogen which is stored in the liver cardiac muscle and central nervous system In the third trimester excess glucose is converted to tri-glycerides which are stored in adipose tissue
Insulin is an important fetal hormone to ensure glucose and other substrates are utilized for growth and storage but in nor-mal circumstances insulin is not required for fetal glucose con-trol The exception is for the infant of the mother with poorly controlled diabetes when transfer of glucose across the placenta is at a higher rate driven by the maternalndashfetal concentration gra-dient This results in increased insulin secretion excess growth and increased storage of glycogen and adipose tissue (macroso-mia) along with increased risk of intracellular hypoxia
Conversely in the fetus affected by severe placental insuffi-ciency transfer of glucose and other nutrients across the placenta is at a lower rate and the fetus is required to metabolize first its own fuel stores and then structural proteins (eg in muscle) to ensure energy delivery to the vital organs assisted by the redis-tribution of blood flow to these organs Should placental function deteriorate further these adaptive responses fail Fetal hypogly-caemia has been described in these circumstances78
When placental nutrition abruptly ceases at birth the healthy neonate is dependent upon endocrine changes to initiate meta-bolic adaptation Insulin levels fall steadily and the action of any residual circulating insulin is overcome by the surge of the coun-ter-regulatory hormones glucagon and the catecholamines This change in the balance of glucoregulatory hormones induces the activity of key enzymes for glycogenolysis (release of glucose from glycogen stores) gluconeogenesis (production of glucose from precursors including glycerol and amino acids) lipolysis (release of free fatty acids and glycerol from adipose tissue stores) and beta-oxidation of fatty acids to produce ketone bodies910 If fasting is prolonged structural protein is broken down to release gluconeogenic amino acids Other than lipolysis and proteolysis all of these processes take place in the liver Glycogenolysis also takes place in cardiac muscle and the central nervous system providing immediate energy (in the form of glucose or lactate)
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
at this crucial time411 Clearly during this catabolic phase of immediate postnatal nutrition prior to the establishment of suck-ling feeds provision of energy for vital organ function is at the expense of growth and fuel storage
The postnatal metabolic transition is characterized by low cir-culating blood glucose concentrations compared to those of older infants and children often for a number of days12 This is almost always of no pathological significance for a number of reasons including differences in the function and metabolic requirements of the brain and importantly the production and utilization of alter-native fuels lactate and ketone bodies which are in plentiful supply in the neonate341213ndash20 An important finding from clinical studies and of clinical relevance to those caring for mothers and babies is that in all groups of infants studied to date those who are breast fed have higher circulating ketone body levels than those who are formula fed even after correcting for blood glucose levels102122
There are circumstances however when hypoglycaemia is severe and prolonged and conditions when alternative fuel pro-duction is also impaired or fails In these circumstances low blood glucose levels do acquire clinical significance The key metabolic processes and the risk factors for impaired metabolic adaptation are summarized in Table 1
Metabolic changes at birth ndash key hormones and metabolic processes and risk factors for impaired metabolic adaptation
Postnatal metabolic
changes
Risk factors
Hormones
insulin falls neonatal hyperinsulinism ndash infant of
diabetic mother or idiopathic
glucagon surge possibly blunted by iv glucose or
formula feeds
Catecholamine surge maternal beta-blocker medication
(Cortisol ndash weak effect) (pituitary or adrenal insufficiency)
Metabolic processes
glygogenolysis preterm intrauterine growth
restriction (iugR) ndash reduced stores
perinatal hypoxia-ischaemia ndash stores
utilized
Hyperinsulinism
maternal beta-blocker medication
glycogen storage disorders
gluconeogenesis Hyperinsulinism
maternal beta-blocker medication
Hepatic dysfunction
Very rare inborn errors of metabolism
lipolysis preterm iugR ndash reduced stores
Hyperinsulinism
maternal beta-blocker medication
Ketogenesis Defects of beta-oxidation of fatty
acids
Hepatic dysfunction
Table 1
paeDiatRiCS anD CHilD HealtH 184 16
Impaired metabolic adaptation
Risk factors for impaired metabolic adaptation vary and may be related to any of the following reduced body fuel stores failure of the normal endocrine changes at birth systemic illnesses which impede function of the liver where the key metabolic processes occur or rarely inborn errors of metabolism (see Table 1)
It is well recognized that significant hypoglycaemia will result in a reduced level of consciousness andor fits However it is always important to be alert for detect and treat an underlying pathology which could be causing both the hypoglycaemia and the abnormal signs Often abnormal signs and hypoglycaemia are co-morbidities eg a primary neurological problem causes both abnormal neurological signs and hypoglycaemia secondary to poor feeding For this reason all possible underlying causes for presentation with hypoglycaemia must be considered and investigations planned accordingly Investigations for inborn errors of metabolism and endocrine disorders are most informa-tive if carried out when blood glucose levels are low
There have been extensive efforts to use data from clinical stud-ies of the human neonate to determine the significance of neonatal hypoglycaemia in terms of neurophysiological neurodevelopmental and neuroradiological sequelae However there are major difficul-ties in interpreting these clinical studies as to date these have been flawed by confounding factors such as immaturity placental insuf-ficiency and co-existing complications by heterogeneity of subjects and by failure to take into account protective mechanisms11423 The evidence from both animal and human studies suggests lsquopurersquo hypo-glycaemic brain injury is rare and for hypoglycaemic brain injury to occur there must be co-existing failure of metabolic adaptation such that alternative fuels are not available There is no evidence that lsquotransitionalrsquo hypoglycaemia in the healthy neonate is associated with acute or long term sequelae and indeed even for babies in the at-risk groups on many occasions protective factors will prevail
Diagnosis of clinically significant hypoglycaemia
lsquoNeonatal hypoglycaemiarsquo is a commonly cited diagnosis most often based on a single blood glucose level and using inaccurate methods of measurement and with disregard for the presence or absence of associated clinical signs In the many published texts and local guidelines there is no consistency of approach For this reason a multinational group of experts attempted to examine critically the evidence on which clinical recommendations should be made1 Fol-lowing detailed analysis the authors considered it impossible to define hypoglycaemia as a single blood glucose level and instead suggested operational thresholds and therapeutic goals They con-cluded that low blood glucose levels accompanied by neurological signs should be investigated and treated regardless of the blood glu-cose level They also pragmatically concluded that a blood glucose level below 10 mmollitre should be treated immediately In babies who are at risk of impaired metabolic adaptation but who have no clinical signs it is recommended that interventions to raise blood glucose level are considered if blood glucose levels are persistently below 20 mmollitre For sick and very low birthweight babies who are likely to have a requirement for intravenous glucose there should be a lsquotherapeutic goalrsquo to maintain blood glucose levels above 25 mmollitre Where there is known hyperinsulinism (a very high-risk condition characterized by high intravenous glucose
2 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
requirements to maintain normoglycaemia) an operational thresh-old and therapeutic goal of 35 mmollitre has been proposed24
Finally there must be careful consideration of the infant of the diabetic mother In extreme and rare cases there may be signifi-cant but transient hyperinsulinism and in these cases the thera-peutic goal must be 35 mmollitre More commonly babies whose mothersrsquo diabetes has been well controlled will have normal lsquotran-sitional hypoglycaemiarsquo or slightly delayed metabolic adaptation while insulin levels fall postnatally There must be careful and repeated clinical assessment including blood glucose monitoring For infants of diabetic mothers who have no evidence of signifi-cant hyperinsulinism and no abnormal clinical signs there is no evidence that the operational threshold for hyperinsulinism must be applied Indeed to do so would result in separation of large numbers of healthy babies from their mothers with the conse-quent impact upon breast feeding and resource allocation25
The operational thresholds for various groups of babies are summarized in Table 2
The guidance relating to operational thresholds is predicated upon the accurate measurement of blood glucose levels It is now well known that the commonly used reagent strips are insufficiently accurate to diagnose hypoglycaemia and monitor at-risk infants and there must be access to equipment which allows immediate and accurate determination of blood glucose levels1426ndash28
Blood glucose monitoring
An accurate method for blood glucose monitoring must be employed as described above The sample should be free flowing venous or from a warm heel such that the blood flows freely without squeezing
Blood of high haematocrit often yields low blood glucose lev-els because of dilution of glucose by red cell water However this is also clinically relevant because polycythaemia is itself a high-risk situation Therefore in polycythaemic infants both the haematocrit and blood glucose level must be monitored and both acted upon accordingly
Operational thresholds for blood glucose levels in the management of babies at risk of impaired metabolic adaptation124
Clinical condition Blood glucose level at which
to consider intervention and
therapeutic goal
all at-risk babies lt10 mmollitre
abnormal neurological
signs
intervene regardless of blood
glucose levelSystematically unwell baby therapeutic goal of 25 mmollitre
at-risk babies no abnormal
neurological signs
persistently lt20 mmollitre
Hyperinsulinism 35 mmollitre
Table 2
paeDiatRiCS anD CHilD HealtH 184 163
Only babies in at-risk groups or babies who have abnormal neurological signs should be subjected to blood glucose monitor-ing (Table 3)
It is important not to commence blood glucose monitoring too soon after birth as to do so would fail to differentiate the baby with incipient hypoglycaemia from the baby undergoing the nor-mal postnatal fall in blood glucose level It is recommended in the otherwise healthy but at-risk baby to wait until around 3 h after birth to make the first blood glucose estimation2528 In prac-tice this is usually before the second feed assuming best practice of offering a baby a breast (or if necessary formula feed) imme-diately after birth Clearly if the baby is unwell or has abnormal clinical signs in the first 3 h they will be treated according to clinical condition which will include intravenous fluids and the therapeutic goal described above would apply
Similarly the temptation to measure blood glucose level shortly (within 2 h) after intravenous glucose has been discon-tinued must be avoided In this circumstance as at birth blood glucose levels fall and then subsequently rise in response to coun-ter-regulation It is this effective rise which must be assessed by blood glucose measurement at least 2 h after a change is made (provided the baby remains clinically well)
Blood glucose levels rise after a feed and fall to a nadir before the subsequent feed As our concern is the lowest blood glucose level during the feed cycle and as this measurement may assist in determining best feed frequency it is important that pre-feed blood glucose concentration is measured There is no clinical value in measuring a post-feed blood glucose level as this may be falsely reassuring and this practice subjects babies to more frequent heel pricks or venesections than is necessary
Finally consideration must be given to when to discontinue blood glucose monitoring This will depend upon the babyrsquos clin-ical condition feeding pattern and underlying disorder or risk factors for impaired metabolic adaptation
Prevention and management of clinically significant hypoglycaemia
In babies at risk of clinically significant hypoglycaemia and who are well enough to tolerate enteral feeds milk feeds are the
At-risk babies for whom blood glucose monitoring is recommended
abnormal neurological signs
Systemically unwell eg suspected or proven infection
hypoxicndashischaemic encephalopathy
preterm (lt 37 weeks)
intrauterine growth restriction (lt 2nd centile and any baby with
signs of wasting)
infant of diabetic mother
polycythaemia
maternal beta-blocker medication
Suspected hyperinsulinism
Suspected inborn error of metabolism or endocrine disorder
Table 3
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
mainstay of prevention For babies who are able to feed orally breast feeding should be first choice and there must be maximal support for the mother to do so This is a key clinical priority for midwives and paediatricians
If there are concerns regarding adequacy of breast feeding to prevent hypoglycaemia the mother should be encouraged to commence expression of milk from very soon after birth If there is insufficient breast milk to prevent babies reaching the opera-tional thresholds described above there should be judicious use of formula milk using only the smallest amount required to keep the babyrsquos glucose in the required range Formula milk in exces-sive quantities has been demonstrated to suppress normal meta-bolic adaptation2122
In babies for whom early enteral feeds are not appropriate or not tolerated or for whom enteral feeding does not prevent blood glucose level falling below operational thresholds intravenous glucose infusion at rates around 4ndash5 mgkgmin (58ndash72 mlkgd of 10 dextrose) are usually sufficient to prevent hypoglycae-mia If blood glucose levels remain below therapeutic goals the rate of infusion may be steadily increased Excess glucose infu-sion over and above that required to maintain the therapeutic goal will stimulate insulin and there is a risk of rebound hypo-glycaemia if high rate glucose infusions are too rapidly reduced Milk feeds if tolerated should be continued if intravenous glu-cose is commenced
If infused volume of glucose solution becomes excessive in order to maintain therapeutic goals or if fluid restriction must be applied more concentrated glucose concentrations must be infused through a central venous line This is particularly rel-evant to the hyperinsulinaemic baby in whom glucose infusion rates in excess of 8ndash10 mgkgmin are required to maintain ther-apeutic goals There is a high risk of severe and brain-damaging hypoglycaemia if treatment is delayed or fails to raise blood glu-cose levels and management of these babies requires consulta-tion with or referral to a specialist centre24
If there is presentation of hypoglycaemia with abnormal clinical signs or a very low blood glucose level (less than 1 mmollitre) this mandates urgent treatment with intravenous glucose The rates of glucose infusion described above are usually sufficient to bring the blood glucose level rapidly to the therapeutic goal without a bolus of glucose being necessary In fact a bolus dose of glucose will result in a peak blood glucose level and then an insulin surge making subsequent management problematical This is minimized by the use of a lsquomini-bolusrsquo should a bolus of glucose be required ndash 200 mg glucosekg (2 mlkg of 10 dextrose)28 Indications for mini-bolus are infants presenting with fits or coma or an lsquounre-cordablersquo or zero blood glucose level A mini-bolus should always be followed with glucose infusion or an increased glucose infusion rate if a baby already receiving intravenous glucose has required a mini-bolus
The temptation to supplement enteral feeds with glucose polymers and energy supplements (eg Duocal) or to use oral glucose gels or solutions (eg Hypostop) should be avoided as this carries a risk of necrotizing enterocolitis is likely to suppress normal metabolic adaptation and will suppress the appetite of the baby for effective oral feeding
Finally there are additional medications which may be employed in specific circumstances (Table 4) More detailed descriptions are given elsewhere242728 Babies who have hypoglycaemia which
paeDiatRiCS anD CHilD HealtH 184 164
is difficult to control by the measures described above and who require these additional treatments should be cared for in a centre which has expertise in metabolic and endocrinological conditions
Summary
Much controversy and confusion has surrounded neonatal hypo-glycaemia but this usually arises as a result of failure to under-stand the processes of normal metabolic adaptation and the fact that hypoglycaemia is a presenting sign rather than a diagnosis in itself Plans for investigation and management must be based upon the most likely underlying cause of impaired metabolic adaptation and take into account the clinical condition of the baby This is counter to the current trend to propose rigid pro-tocols and algorithms and re-introduces the value of detailed clinical evaluation and decision making The mainstay of man-agement is close clinical observation of vulnerable infants and energy provision tailored to their individual needs whilst avoid-ing excessively invasive management (namely unnecessary sep-aration of mother and baby routine or excessive formula milk supplementation or intravenous glucose administration) which themselves inhibit protective metabolic responses and impede successful establishment of breast feeding
ReFeRenCeS
1 Cornblath m Hawdon Jm Williams aF et al Controversies regarding
definition of neonatal hypoglycemia Suggested operational
thresholds Pediatrics 2000 105 1141ndash1145
2 Cornblath m ichord R Hypoglycemia in the neonate Semin
Perinatol 2000 24 136ndash149
3 Vannucci RC Vannucci SJ Hypoglycaemic brain injury Semin
Neonatol 2001 6 147ndash155
4 Rozance pJ Hay WW Hypoglycaemia in newborn infants features
associated with adverse outcomes Biol Neonate 2006 90 74ndash86
5 Hawdon Jm Hypoglycaemia in newborn infants defining the
features associated with adverse outcomes ndash a challenging remit
Biol Neonate 2006 90 87ndash88
6 Williams aF neonatal hypoglycaemia clinical and legal aspects
Semin Fetal Neonatal Med 2005 10 363ndash368
7 Soothill pW nicolaides KH Campbell S prenatal asphyxia
hyperlacticaemia hypoglycaemia and erythroblastosis in growth
retarded fetuses BMJ 1987 294 1051ndash1053
Additional medication in specific conditions (if these are required there must also be referral to a specialist centre)
Medication Indication
glucagon intramuscular bolus dose of 200 μgkg
transient rise in blood glucose level eg
when difficulty re-siting intravenous infusion
Diazoxide Hyperinsulinism
Hydorcortisone pituitary or adrenal insufficiency
Table 4
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
8 Hawdon Jm Ward platt mp mcphail S Cameron H Walkinshaw Sa
prediction of impaired metabolic adaptation by antenatal Doppler
studies in small for gestational age fetuses Arch Dis Child 1992
67 787ndash792
9 Deshpande S Hawdon Jm et al adaptation to extrauterine life in
Rodeck C Whittle m eds Fetal medicine Basic Science and Clinical
practice edinburgh Churchill livingstone 1999
10 Ward platt m Deshpande S metabolic adaptation at birth Semin
Fetal Neonatal Med 2005 10 341ndash350
11 eyre Ja Stuart ag Forsyth RJ Heaviside D Bartlett K glucose
export from the brain in man evidence for a role for astrocytic
glycogen as a reservoir of glucose for neural metabolism Brain Res
1994 28 349ndash352
12 Hawdon Jm Ward platt mp aynsley-green a patterns of metabolic
adaptation for preterm and term infants in the first neonatal week
Arch Dis Child 1992 67 357ndash365
13 Hawdon Jm Ward platt mp aynsley-green a prevention and
management of neonatal hypoglycaemia Arch Dis Child Fetal
Neonatal Ed 1994 70 F60ndash64
14 Hawdon Jm Hypoglycaemia and the neonatal brain Eur J Paediatr
1999 158 S9ndash12
15 massieu l Haces ml montiel t Hernaacutendez-Fonseca K acetoacetate
protects hippocampal neurons against glutamate-mediated neuronal
damage during glycolysis inhibition Neuroscience 2003 120
365ndash378
16 yamada Ka Rensing n thio ll Ketogenic diet reduces
hypoglycaemia-induced neuronal death in young rats Neurosci Lett
2005 385 210ndash214
17 nehlig a Brain uptake and metabolism of ketone bodies in animal
models Prostaglandins Leukot Essent Fatty Acids 2004 70
265ndash275
18 Hernaacutendez mJ Vannucci RC Salcedo a Brennan RW Cerebral blood
flow and metabolism during hypoglycemia in newborn dogs
J Neurochem 1980 35 622ndash628
19 Vannucci RC nardis ee Vannucci SJ Campbell pa Cerebral
carbohydrate and energy metabolism during hypoglycaemia in
newborn dogs Am J Physiol 1981 256 H1659ndashH1666
20 anwar m Vannucci RC autoradiographic determination of regional
cerebral blood flow during hypoglycaemia in newborn dogs Pediatr
Res 1988 24 41ndash45
21 Hawdon Jm Williams aF et al Formula supplements given to
healthy breastfed preterm babies inhibit postnatal metabolic
adaptation results of a randomised controlled trial Arch Dis Child
2000 82 a30
paeDiatRiCS anD CHilD HealtH 184 16
22 de Rooy l Hawdon Jm nutritional factors that affect the postnatal
metabolic adaptation of full-term small- and large-for gestational
age infants Pediatrics 2002 109 e42
23 Hawdon Jm Hypoglycaemia and brain injury ndash when neonatal
metabolic adaptation fails in levene m ed Fetal and neonatal
neurology and neurosurgery edinburgh Churchill livingstone in
press
24 Hussain K Congenital hyperinsulinism Semin Fetal Neonatal Med
2005 10 369ndash376
25 acolet D Diabetes in pregnancy Caring for the Baby after Birth
CemaCH 2007 2
26 Hussain K Sharief n the inaccuracy of venous and capillary blood
glucose measurement using reagent strips in the newborn period
and the effect of haematocrit Early Hum Dev 2000 57 111ndash121
27 Hawdon Jm Disorders of blood glucose homeostasis in the neonate
in Rennie Jm ed Robertonrsquos textbook of neonatology 4th edn
edinburgh Churchill livingstone 2005
28 Deshpande S Ward platt mp the investigation and management
of neonatal hypoglycaemia Semin Fetal Neonatal Med 2005 10
351ndash361
Practice points
bull identify risk factors for impaired metabolic adaptation
bull Clinical monitoring including accurate blood glucose
measurement for at-risk babies
bull Feed at-risk babies soon after birth and maintain thermal
homeostasis
bull take first blood glucose level at 3ndash4 h of age
bull intervene in at-risk baby with no clinical signs if two
consecutive blood glucose measurements lt 20 mmollitre
bull intervene in any baby with blood glucose measurement
lt 10 mmollitre
bull intervene in any baby with abnormal clinical signs regardless
of blood glucose level
bull investigate for underlying cause of failure of metabolic
adaptation
bull maintain lactation and breast feeding
5 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Resuscitation of the term and premature babyJonathan Wyllie
Abstractalthough most newly born babies establish normal respiration and
circulation without help up to 1minus2 may require some resuscitation
or stabilization Babies who do not establish adequate regular normal
breathing or who have a heart rate of less than 100 beatsmin or other
problems such as prematurity may require assistance the differences in
approach to the resuscitation of such babies originate in the physiology
and pathophysiology of acute asphyxia at birth However management
of airway and breathing remain the key features of resuscitation and
where cardiac depression has occurred this is nearly always due to hy-
poxia secondary to respiratory compromise therefore most babies will
respond within 2minus3 min of effective aeration of the lungs and the need
for intubation chest compressions or drugs is rare the international
liaison Committee on Resuscitation (ilCoR) evaluated evidence in 2000
and 2005 in order to provide guidelines for resuscitation they will do
so again for 2010 this evidence is limited in terms of both quantity and
quality and controversies still exist more research is needed to ensure
that our future actions are based upon evidence rather than history this
article will review the recommended approach to resuscitation as well as
some newer evidence
Keywords guidelines neonatal newborn premature resuscitation
Background
In the UK 669 601 babies were born alive in 2006 and most made the transition to extrauterine life without problems Those babies who did not establish adequate regular normal breathing or who had a heart rate of less than 100 beatsmin may have required assistance1 Factual evidence concerning the true requirement for resuscitation at birth is sparse Up to 10 of newborns may require some assistance to begin breathing with less than 1 needing extensive resuscitation2 However just because a baby received resuscitation does not necessarily mean that it was required and rates of intervention may be altered by educa-tion34 or the personnel present at deliveries5 In a UK tertiary centre with a standard approach to resuscitation at birth up to 12 of all babies received some airway assistance with just over 1 being intubated3 In Sweden only 1 of babies over 2500 g required mask or endotracheal tube ventilation at birth of which most responded to the former4
Jonathan Wyllie MBChB FRCPCH is Consultant Neonatologist at the James
Cook University Hospital Marton Road Middlesbrough TS4 3BW UK
paeDiatRiCS anD CHilD HealtH 184 16
Sometimes it is possible to predict babies who are likely to have respiratory depression at birth and to have appropriate per-sonnel present at delivery Guidelines for attendance at deliveries will vary with institution but even when almost 40 of deliv-eries are attended there may still be a further 15 of babies who require unexpected resuscitation5 a proportion that seems to remain whatever changes are made
The physiology of babies requiring help at birth has been summarized previously167 It allows a logical approach to resus-citation (Figure 1) when evidence is lacking and may prompt further research
Resuscitation at birth
PreparationAt birth resuscitation is more likely in babies with intrapartum evidence of significant fetal compromise those less than 35 weeksrsquo gestation those delivering vaginally by the breech and in multiple births Personnel trained in newborn resuscitation should be available at every delivery1 Someone experienced in tracheal intubation and advanced resuscitation should also be easily available for normal low-risk deliveries in hospital and ideally in attendance for deliveries with an increased likelihood of needing resuscitation In the latter cases the equipment and environment can be prepared beforehand including a discussion with the parents Wash your hands put on gloves and consider what help may be needed
Cord clampingAt birth it has long been known that delay in clamping the cord will lead to less anaemia in babies and reduce subsequent iron deficiency8 However few hospitals have practised this interven-tion due to worries about hypothermia and the need to resusci-tate or stabilize babies In developed countries the advantages seemed to be outweighed by the potential disadvantages A recent randomized controlled study of delayed clamping of the cord in premature babies found that the intervention group had less late-onset sepsis and fewer intraventricular haemorrhages9 This is a low-risk strategy which needs further evaluation in order to introduce it without increasing other risk factors in pre-mature deliveries
Assessment and temperature controlAssessment and temperature control for the newborn baby should occur at all deliveries The assessment indicates the need for resuscitation Babies may vary from 23 to 40+ weeksrsquo ges-tation and in weight from 500 to 5000 g They are born naked and wet and if left cannot cope with an environmental tem-perature of less than 32degC However if the term baby is imme-diately dried put skin-to-skin with the mother and covered the delivery room temperature can be as low as 25ndash28degC Obviously the smaller the baby the greater the surface area to mass ratio and the greater the risk of hypothermia Compromised babies are particularly vulnerable10 and hypothermia will lower oxygen tension11 increase metabolic acidosis12 and inhibit surfactant production13
An effective method of maintaining the temperature of prema-ture babies less than 28 weeksrsquo gestation is wrapping them with plastic before drying and then placing them under a radiant
6 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Dry the babyRemove any wet towels and cover
Start the clock or note the time
Give 5 inflation breathsLook for a response
If no increase in heart rate look for chest movement
Re-check head positionApply Jaw thrust
Repeat inflation breathsLook for a response
If no increase in heart rate look for chest movement
Try alternative airway opening manoeuvresRepeat inflation breaths
Look for a response
If no increase in heart rate look for chest movement
If the heart rate is not detectable or slow (lt60)Start compressions
3 compressions to each breath
Reassess heart rate every 30 secondsConsider venous access and drugs
Assess colour tone breathing and heart rate
Open the airway
If not breathing
If still not breathing
If no response
If still no response
When the chest is moving
If meconium present
Baby breathing wellDo not suction the airway
Baby floppy and not breathing wellConsider inspection and suction before
inflation breaths
Head in neutral position
Inflation breathsUse a well-fitting face mask
connedted to a
pressure-limited gas supply
Each breath 2ndash3 seconds
duration at 30 cm H2O for a
term baby
Get help from a second personto support the airway andor
inspect the oropharynx under
direct vision and consider
suction andor insert an
oropharyngeal airway
Chest compressionsCompvent ratio 31
Rate 120 events per minute
Ensure the chest moves with each ventilation breath
If breathingReassess heart rate and monitor baby
If heart rate is satisfactory but increasingContinue ventilation breaths at about 30 per
minute until baby is breathing adequately
If heart rate is satisfactory but increasingContinue ventilation breaths at about 30 per
minute until baby is breathing adequately
If heart rate is increasingStop compressions
Continue ventilation breaths at about 30 per
minute until baby is breathing adequately
If the chest is not movingRecheck head position and repeat inflation
breaths If competent consider intubation
If the chest is still not movingThe airway is the problem
Figure 1 newborn life support (Courtesy of the Resuscitation Council uK)
heater14 There is a small risk of hyperthermia so the temperature must be monitored carefully
An assessment is made of the babyrsquos colour tone respira-tions and heart rate127 The most important of these is heart rate and a stethoscope is more reliable than cord pulsation15 How-ever saturation monitors may offer a more reliable assessment of both heart rate and colour16 but their interpretation requires a detailed knowledge of normal saturations at birth at differing gestations A baby who is apnoeic and floppy in the absence of neurological disease is unconscious and likely to be in terminal apnoea however this does not change the initial approach other
paeDiatRiCS anD CHilD HealtH 184 167
than the need to summon help early APGAR scores are never calculated to guide resuscitation
Airway
If a baby is in primary apnoea then with an open airway the first gasp will start to aerate the lungs and most babies will be able to lsquoresuscitatersquo themselves as shown in physiological stud-ies on animals Neutral positioning of the babyrsquos head chin lift jaw thrust oropharyngeal airways and endotracheal intubation may all be helpful in certain situations if performed correctly17
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Endotracheal intubationThe placement of an endotracheal tube has long been the gold standard of airway control and this remains true in the unconscious baby if it is correctly sized placed and fixed in a timely manner However experience is directly related to effec-tiveness in endotracheal intubation1819 and the success rate of less experienced clinicians such as a resident (STA1-3) or a fel-low (STA3-5) is lower varying between 33 and 68 Even senior neonatologists often take longer than guidelines recom-mend19 Experienced clinicians may judge correct endotracheal position visually or by an increase in heart rate with the first breaths but detection of exhaled carbon dioxide will give more rapid confirmation in larger babies12171920 and this can be par-ticularly useful for less experienced clinicians or those supervis-ing them However not all systems for the detection of exhaled carbon dioxide work in the smallest premature infants
Laryngeal masksLaryngeal masks may be effective for ventilating term newborn babies but there are few data for small premature infants There have been reports of dislodged laryngeal airways during paedi-atric arrests when chest compressions have been administered Although success of placement at first attempt by paediatri-cians is greater with a laryngeal mask than with an endotra-cheal tube21 the only and small randomized controlled trial in the delivery room favoured endotracheal intubation when per-formed by an anaesthetist22 Based mainly upon case reports the laryngeal mask can be recommended when positioning and mask ventilation and endotracheal intubation have failed to secure the airway but not as yet as a primary method of airway control
MeconiumIn 2000 Wisewell et al23 reported a large randomized controlled trial showing that tracheal intubation and suctioning of meco-nium-stained but vigorous babies at birth did not reduce the incidence or severity of meconium aspiration syndrome More recently another randomized trial has now shown that suction-ing on the perineum similarly offers no benefit24 Neither of these practices is recommended but intubation and suction of meconium from the trachea of non-vigorous babies born through meconium-stained liquor is still recommended
Breathing
In the apnoeic baby the first breaths establish the resting lung volume and aerate the fluid-filled alveoli This mechanical effect aided by surface tension within the alveoli causes the initial fall in pulmonary vascular resistance Experimentally this effect occurs even if the lungs are ventilated with nitrogen but is increased when air is used presumably due to the vasodilator effect of 21 oxygen The mechanical stretching of the lung also triggers the activation of cyclo-oxygenase beginning the production of prostacyclin Bradykinin is produced which has a further direct vasodilator effect and also possibly via prostacyclin Therefore adequate airway control and passive ventilation is vital not only because babies requiring resuscitation at birth have an almost uniformly respiratory aetiology but also in order to promote post-natal adaptation and reverse any maladaptation
paeDiatRiCS anD CHilD HealtH 184 16
In term babies peak ventilatory pressures of 20ndash30 cmH2O may be required but the minimal pressure needed to achieve an improvement in heart rate should be used or if there is no response chest wall movement Longer breaths at lower pressure may be more effective in displacing alveolar fluid and establish-ing the resting lung volume in lungs with sufficient surfactant and may improve initial oxygenation However premature new-borns are obviously physiologically and anatomically less pre-pared for delivery than infants at term Over-inflation has been implicated in histological lung damage in animal models and high tidal volumes appear to be equally damaging whether given before or immediately after administration of surfactant How-ever the same effect is not seen if these excessive tidal volumes are delivered 15 min after administration of surfactant2526 It is now thought that both excess end expiratory volume and inad-equate end-expiratory volume may cause lung damage2728 In premature infants it would therefore seem sensible to use lower pressures of 20ndash25 cmH2O12 delivered in a controlled way to prevent over-inflation and to apply positive end-expiratory pres-sure (PEEP) to prevent damage from under-inflation PEEP also improves both lung compliance and gas exchange2930 Without PEEP the airways collapse during the expiratory phase in animal models of newborn resuscitation
If animal data can be extrapolated it would also seem appro-priate to give surfactant as soon as possible to premature babies in order to ameliorate damage2526
The majority of newborn infants requiring resuscitation will re-establish regular respiration after administration of a few breaths which may be due to Headrsquos paradoxical reflex by which the inflation triggers an inspiratory effort
VentilationOnce the lungs are aerated if the newborn remains apnoeic ventilation should be continued at 30ndash60 breathsmin avoiding hyperventilation and using the minimum pressure possible to maintain a heart rate greater than 100 beatsmin
Face mask the majority of infants who require ventilation receive it via a face mask This may be attached to a bagvalve system with a spring lsquoblow offrsquo system or a lsquoT-piecersquo with a set flow and pressure It is important to realize that the bagvalve system is flow sensitive and that the harder the operator presses the greater the flow and the higher the delivered pressure In fact 60 cmH2O can be achieved with vigorous squeezing of a self-inflating bag Therefore it may be advantageous that most opera-tors are unlikely to be as effective as they suppose in creating a seal with the mask31 This is a skill that requires tuition and prac-tice31 In delivering a set pressure T-piece systems such as the Tom Thumbcopy or Neopuffcopy perform better than any bagminusvalve system but require a gas supply There is no evidence that lung compliance can be assessed using any bag system
Continuous airway pressure case series have suggested that early or delivery room use of continuous positive airway pres-sure (CPAP) in premature babies may reduce chronic lung dis-ease There have been two randomized trials of which one was a pilot study The data from the COIN trial do not show any advan-tage other than a reduction in intubation and surfactant use in the intervention group However an excess of pneumothorax
8 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
was also reported The Vermont Oxford Network and the SUP-PORT trials will provide further data but at present the delivery room use of CPAP cannot be widely recommended and should be limited to those units experienced in its use or taking part in research
Air or oxygen oxygen has been in widespread use for resuscita-tion at birth since the 1930s and even hyperbaric oxygen was seriously supported in the 1960s For many years there have been concerns about tissue damage from oxygen deprivation during and after resuscitation It became evident in the 1950s that unrestricted oxygen therapy could have serious conse-quences for future vision More recently concerns have been raised about potential adverse effects on respiratory physiology cerebral circulation and tissue damage from oxygen free radicals even during resuscitation A meta-analysis of four human studies demonstrated a reduction in mortality and no evidence of harm in infants resuscitated in air versus 100 oxygen3233 However there are several significant methodological concerns with these studies and the results should be interpreted with caution There is insufficient evidence to recommend any specific concentration of oxygen to be used for newborn resuscitation Monitoring the oxygen saturation of babies may be helpful but as yet there are no time-related normal target ranges and healthy term babies may take up to 10 min to achieve preductal oxygen saturation of greater than 95 and up to 60 min to achieve this postductally
There is therefore equipoise which would be open to an appropriate randomized controlled trial In the meantime the evidence only supports use of either 21 or 100 oxygen It is provoking to realize that if air had been in constant use since the 1930s there would be insufficient evidence for use of supple-mental oxygen
Circulation
Early resuscitation (temperature control airway breathing) provides oxygenated blood in the pulmonary arterioles which if returned to the heart causes the rate to increase34 If due to acidosis and hypoxia the circulation is ineffective then chest compressions may be needed They should be commenced when the heart rate remains below 60min despite effective airway and breathing management127 The best technique is using two hands to encircle the chest1 A ratio of three compressions to one breath is internationally accepted127 but has no evidence to support it Research has shown that neither compressions nor drugs will work in this situation without oxygenated blood so effective lung aeration and ventilation is essential A logical approach would be to fill the alveoli with air and to compress the chest until they are empty However training and teamwork require an agreed ratio which has therefore not changed since guidelines were first agreed internationally Success is assessed by an increase in heart rate which should therefore be assessed every 30 s Compressions stop when the spontaneous heart rate is greater than 60 beatsmin
In hypoxic newborn animal models successful resuscitation can restore cardiac output and blood pressure to levels above baseline within 5ndash10 min However it should be noted that there is a decline to 30 lower than basal levels within 2 h and that blood pressure is relatively spared suggesting an even greater
paeDiatRiCS anD CHilD HealtH 184 16
reduction in tissue perfusion This should be considered in the later care of any neonate who was hypoxic at birth
Drugs
Neonatal bradycardia at birth is almost always due to hypoxia plusmn acidosis and therefore drugs are rarely needed Adrenaline (epi-nephrine) is reported as being used in between 1 and 4 babies per 2000 births which is a large variation in practice Reported success is also variable and must be interpreted in light of this variation The use of drugs in extremely premature infants is con-troversial Some data suggested good outcomes for babies below 28 weeksrsquo gestation given adrenaline but these were flawed by high numbers of babies receiving resuscitative drugs some before the airway had been appropriately managed Audit data now suggest a poor outcome such that many clinicians would now council against the use of adrenaline and other drugs to resuscitate extremely premature newborn babies
Adrenaline (epinephrine)In 2003 a Cochrane review of randomized controlled trials involv-ing adrenaline use for resuscitation of neonates was unable to identify a single clinical trial35 Despite the lack of human neo-natal data animal models show the potential of adrenaline in asphyxial cardiac arrest and it is reasonable to use it when ade-quate ventilation and chest compressions have failed to increase the heart rate above 60 beatsmin Use 10ndash30 μgkg intrave-nously and preferably via an umbilical venous line The tracheal route cannot be recommended but if used it is likely that doses within this range will be ineffective and 100 μgkg might be tried However the safety of such doses has not been studied
BicarbonateThe use of bicarbonate has long been controversial but many of the concerns relate to the rapid correction of acidosis in neonates after resuscitation or the routine use of bicarbonate infusion nei-ther of which can be advocated There are no published human neonatal data to support its use although some exist from animal studies Animal data have also shown that the binding of adren-aline to receptors in the myocardium is significantly impaired by lactic acidosis and recent work on human lymphocyte beta-adrenergic receptors supports this view Whether this is also true of the more important alpha receptors is unknown In practice reversing intracardiac acidosis may improve myocardial function and assist in achieving a return of spontaneous circulation 1ndash2 mmolkg of bicarbonate may be given but this remains a contro-versial area
VolumeVolume expansion should only be given when it is suspected that the baby has suffered blood loss or the infant appears to be in shock (pale poor perfusion weak pulse) and has not responded adequately to other resuscitative measures If there is no history suggestive of blood loss shock is most likely to be due to myo-cardial dysfunction in which case fluids should be administered cautiously The most logical replacement fluid would be blood but in its absence isotonic crystalloid rather than albumin is the solution of choice given in 10 mlkg aliquots and observing the response Three randomized trials in neonates have shown
9 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
isotonic crystalloid to be as effective as albumin for the treat-ment of hypotension but none has examined either the relative or actual effectiveness in resuscitation A recent blinded randomized study comparing normal saline albumin or no volume expansion in a normovolaemic asphyxiated neonatal animal model showed that volume expansion was not beneficial and made a number of parameters worse36
NaloxoneNaloxone is not recommended as part of the initial resuscita-tion of newborns with respiratory depression Before it is given supporting ventilation should have restored the heart rate and colour The dose is 100 μgkg intravenously or intramuscularly Tracheal administration cannot be recommended Although administration of naloxone to neonates who have been exposed to maternal opioids during labour is a practice of long-standing it lacks the proper evidence of efficacy
Non-response to resuscitation
There are few more frightening situations professionally than applying the correct interventions in resuscitating or stabilizing a baby and getting no response Each stage must be adequately performed before moving onto the next and this requires regular reassessment When experienced help is needed at a newborn resuscitation it is usually the airway and ventilation that require correction If the heart rate does not increase this usually means that the lungs have not been successfully aerated In some cases however it may mean that the heart cannot respond as the cir-culation is inadequate In this situation the only way to check that the lungs have been successfully aerated is to see the chest move with ventilation or to obtain evidence of ventilation from a detector of exhaled carbon dioxide If you do not see chest movement after another five breaths the most likely cause is an obstructed airway either due to incorrect positioning or because the jaw has not been drawn forwards An oropharyngeal airway can be very helpful at this point especially in the term baby Only very occasionally is the airway blocked by mucus vernix blood or meconium but if the airway is guaranteed and there is no heart rate response or chest movement this should be sought by direct suction of the trachea even in the absence of any meconium staining of liquor Pneumothoraces can occur spontaneously after delivery but are rare at resuscitation carried out with pressure-limited devices Equally rare are diaphragmatic hernias that have not been diagnosed antenatally giving problems at resuscitation
If the chest is moving but the heart rate has not responded to resuscitation consider rare possibilities such as fetal blood loss pneumothorax or heart block (mothers with undiagnosed systemic lupus erythematosis delivered for fetal bradycardia) as possibilities With adequate ventilation there is no evidence of oxygen concentrations less than 100 being responsible for prolonged bradycardia or failure to respond although current practice would support increasing the delivered oxygen concen-tration if resuscitation had been commenced using air
Outcome
The prognosis for the full-term baby subjected to sudden acute asphyxia is usually good provided the episode does not last for
paeDiatRiCS anD CHilD HealtH 184 17
long Most babies resuscitated from primary apnoea have no sequelae secondary to the resuscitation Many babies who start to breathe again regularly within 20 min of the circulation being restored recover completely but it is rare for a baby who is still gasping after 30 min to recover
The prognosis for the preterm baby of less than about 34 weeksrsquo gestation subjected to severe acute anoxia is less predict-able This is because of the risk of secondary intraventricular haemorrhage or periventricular intracerebral haemorrhage andor infarction after even a relatively brief asphyxial episode espe-cially in the period immediately around birth
The effects of chronic hypoxia are also difficult to predict but a reasonably clear idea of the extent of the problem should be obtainable within 36ndash48 h of the original chronic asphyxial insult A mild short-lasting state of hyperexcitability usually car-ries a good prognosis even if there is seizure activity but more severe symptoms can be associated with permanent handicap This is seen especially in infants with encephalopathy requiring ventilation
REFERENCEs
1 Biarent D Bingham R Richmond S et al european Resuscitation
Council guidelines for Resuscitation 2005 Section 6 paediatric life
support Resuscitation 2005 67(suppl 1) S97ndashS133
2 international liaison Committee on Resuscitation part 7 neonatal
resuscitation Resuscitation 2005 67 293ndash303
3 Singh J Santosh S Wyllie J mellon a effects of a course in
neonatal resuscitation - evaluation of an educational intervention
on the standard of neonatal resuscitation Resuscitation 2006 68
385ndash389
4 palme-Kilander C methods of resuscitation in low-apgar-score
newborn infants - a national survey Acta Paediatr 1992 81
739ndash744
5 Kroll l twohey l Daubeney p et al Risk factors at delivery and
the need for skilled resuscitation Eur J Obstet Gynecol Reprod Biol
1994 44 175ndash177
6 Wyllie Jp Resuscitation of the newborn The Foundation Years
2007 3(4) 153ndash157
7 Richmond S ed newborn life Support Resuscitation at Birth
london Resuscitation Council 2006
8 Ceriani Cernadas Jm Carroli g pelligrine l et al the effect of timing
of cord clamping on neonatal venous hematocrit values and clinical
outcome at term a randomized controlled trial Pediatrics 2006
117 e779ndashe786
9 mercer JS Vohr BR mcgrath mm padbury JF Wallach m oh W
Delayed cord clamping in very preterm infants reduces the incidence
of intraventricular hemorrhage and late-onset sepsis a randomized
controlled trial Pediatrics 2006 117 1235ndash1242
10 Dahm lS James lS newborn temperature and calculated heat loss
in the delivery room Pediatrics 1972 49 504ndash513
11 Stephenson J Du J tk o the effect of cooling on blood gas
tensions in newborn infants J Pediatr 1970 76 848ndash852
12 gandy gm adamsons Jr K Cunningham n Silverman Wa James lS
thermal environment and acid-base homeostasis in human infants
during the first few hours of life J Clin Invest 1964 43 751ndash758
13 gluck l Kulovich mV eidelman ai et al Biochemical development
of surface activity in mammalian lung pulmonary lecithin synthesis
0 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
in the human fetus and newborn and etiology of the respiratory
distress syndrome Pediatr Res 1972 6 81ndash99
14 Vohra S Roberts RS Zhang B Janes m Schmidt B Heat loss
prevention (Help) in the delivery room a randomised controlled
trial of polyethylene occlusive skin wrapping in very preterm infants
J Pediatr 2004 145 750ndash753
15 owen CJ Wyllie Jp Determination of heart rate in babies at birth
Resuscitation 2004 60 213ndash217
16 orsquoDonnell Cp Kamlin Co Davis pg Carlin JB morley CJ Clinical
assessment of infant colour at delivery Arch Dis Child Fetal
Neonatal Ed 2007 92 F465ndashF467
17 international liaison Committee on Resuscitation part 13 neonatal
Resuscitation guidelines Circulation 2005 112(suppl 24)
iV188ndashiV195
18 leone ta Rich W Finer nn neonatal intubation Success of
pediatric trainees J Pediatr 2005 146 638ndash641
19 orsquoDonnell Cp Kamlin Co Davis pg morley CJ endotracheal
intubation attempts during neonatal resuscitation success
rates duration and adverse effects Pediatrics 2006 117
e16ndash21
20 Repetto Je Donohue pa-CpK Baker SF Kelly l nogee lm use of
capnography in the delivery room for assessment of endotracheal
tube placement J Perinatol 2001 21 284ndash287
21 gandini D Brimacombe JR neonatal resuscitation with laryngeal
mask airway in normal and low birth weight infants Anesth Analg
1999 89 642ndash643
22 esmail n Saleh m ali a laryngeal mask airway versus endotracheal
intubation for apgar score improvement in neonatal resuscitation
Egypt J Anesthiol 2002 18 115ndash121
23 Wiswell te gannon Cm Jacob J et al Delivery room management
of the apparently vigorous meconium-stained neonate results of
the multicenter international collaborative trial Pediatrics 2000
105 1ndash7
24 Vain ne Szyld eg prudent lm Wisewell te aguilar am Vivas ni
oropharyngeal and nasopharyngeal suctioning of meconium-stained
neonates before delivery of their shoulders multicentre randomised
controlled trial Lancet 2004 364 597ndash602
25 Bjorklund lJ ingimarsson J Curstedt t larsson a Robertson B
Werner o lung recruitment at birth does not improve lung function
in immature lambs receiving surfactant Acta Anaes Scand 2001 45
986ndash993
26 Bjorklund lJ ingimarsson J Curstedt t et al manual ventilation
with a few large breaths at birth compromises the therapeutic effect
of subsequent surfactant replacement in immature lambs Pediatr
Res 1997 42 348ndash355
paeDiatRiCS anD CHilD HealtH 184 17
27 taskar V John J evander e Robertson B Jonson B Surfactant
dysfunction makes lungs vulnerable to repetitive collapse and re-
expansion Am J Respir Crit Care Med 1997 155 313ndash320
28 muscedere Jg mullen JB gan K Slutsky aS tidal ventilation at low
airway pressures can augment lung injury Am J Respir Crit Care Med
1994 149 1327ndash1334
29 nilsson R grossman g Robertson B Bronchiolar epithelial lesions
induced in the premature rabbit neonate by short periods of artificial
ventilation Acta Pathol Microbiol Scand 1980 88 359ndash367
30 probyn me Hooper SB Dargaville pa et al positive end expiratory
pressure during resuscitation of premature lambs rapidly improves
blood gases without adversely affecting arterial pressure Pediatr
Res 2004 56 198ndash204
31 Wood Fe morley CJ Dawson Ja et al improved techniques
reduce face mask leak during simulated neonatal resuscitation
study 2 Arch Dis Child Fetal Neonatal Ed in press doi101136
adc2007117788
32 tan a Schulz a orsquoDonnell CpF Davis pg air versus oxygen for
resuscitation of infants at birth Cochrane Database Syst Rev 2004
(3) CD002273
33 Davis pg tan a orsquoDonnell Cp Schulze a Resuscitation of newborn
infants with 100 oxygen or air a systematic review and meta-
analysis Lancet 2004 364 1329ndash1333
34 Dawes g Fetal and neonatal physiology Chicago year Book
publisher 1968 p 141ndash159
35 Ziino aJa Davies mW Davis pg epinephrine for the resuscitation
of apparently stillborn or extremely bradycardic newborn infants
Cochrane Database Syst Rev 2003 (2) CD003849
36 Wyckoff m garcia D margraf l perlman J laptook a Randomized
trial of volume infusion during resuscitation of asphyxiated neonatal
piglets Pediatr Res 2007 61 415ndash420
Practice points
bull Resuscitation at birth is different from that at all other times
of life
bull a standard approach can be applied to most newborn
resuscitation
bull guidelines are based on a rigorous evaluation of evidence
where possible
bull evidence is sparse but evolving
bull most preterm babies require stabilization rather than
resuscitation
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Acidndashbase physiology and blood gas interpretation in the neonateSusern tan
morag Campbell
Abstractacidndashbase balance describes the complex processes that work to main-
tain a stable extracellular pH for optimal cellular function the process
of balancing the production and neutralization of tissue acid provides a
great challenge for newborn infants who have significantly higher rates
of acid production than adults Factors which help maintain a stable
acidndashbase balance include buffers the respiratory system and renal sys-
tem Both intracellular and extracellular buffers resist changes in pH
the most important extracellular buffer system for maintaining stable
pH is the bicarbonate system in response to acidosis or alkalosis the
respiratory system balances the production of acid with the clearance
of Co2 by altering respiratory rate the kidneys provide a delayed but
sustained response to pH imbalance by excreting either acidic or alkaline
urine in response to systemic acidosis and alkalosis respectively in sick
premature infants these systems have a limited capacity completely to
control pH this review discusses the physiology of the three systems
which control acidndashbase balance patterns of clinical abnormalities in
acidndashbase status and their underlying causes are discussed We present
a systematic approach to blood gas analysis and interpretation in new-
born infants
Keywords acidosis alkalosis bicarbonate bloodndashgas analysis
metabolic pH
Introduction
Blood gas analysis is a routine procedure performed on newborn babies receiving respiratory support in the neonatal intensive care The combination of invasive and non-invasive assessment of ventilation and oxygenation enables clinicians appropriately to modify respiratory care according to each individual babyrsquos rapidly changing clinical status
Understanding the fundamentals of acidndashbase balance helps us to use blood gas analysis not only to assess respiratory sta-tus but also to provide information on metabolic status and the adequacy of tissue perfusion
Susern Tan MBBS MRCP is Clinical Fellow at the Neonatal Intensive Care
Unit 6th Floor North Wing St Thomasrsquo Hospital London SE1 7EH UK
Morag Campbell MBChB MRCP is Consultant Neonatologist at the
Neonatal Intensive Care Unit 6th Floor North Wing St Thomasrsquo
Hospital London SE1 7EH UK
paeDiatRiCS anD CHilD HealtH 184 17
What is understood by acid-base balance
Acidndashbase balance refers to the complex physiological processes used by the body to maintain a stable extracellular pH1 A serum pH within the range of 735ndash745 provides the ideal environment for cellular metabolism Maintaining a stable pH is critical as the metabolic activity of proteins is pH dependent and small changes in hydrogen ion (H+) concentration can potentially alter physio-logical function
Acids are substances that yield free H+ in solution while a base accepts H+ and in solution combines with an acid to neu-tralize it In the normal metabolic state H+ are continuously pro-duced and neutralized to maintain a steady pH balance12 The rate of H+ production is two to three times higher in neonates because of their rapid growth rates and increased acid production from protein turnover and bone mineralization The challenge of maintaining a stable pH through processing and neutralizing H+ is therefore greatest in newborn infants
Using exact values of H+ concentration to assess acidndashbase status is cumbersome and it is more commonly expressed as pH defined by the equation
pH = minuslog H+
Maintaining acidndashbase balance
The balance between production and excretion of acids in the body is controlled by buffer systems which have an immediate effect and by the respiratory and the renal systems
Buffer systemsBuffer solutions resist change in pH when acid or alkali is added due to their capacity to absorb or give up H+ The three main buffer systems in the body are the bicarbonate phosphate and protein systems1ndash3 The protein and phosphate buffer systems are intracellular and act as lsquosinksrsquo for extracellular H+ which are exchanged with intracellular potassium (K+) and sodium ions (Na+) In an acute metabolic acidosis hyperkalaemia may develop due to this H+ exchange4
The bicarbonate buffer system is extracellular and consists of a mixture of carbonic acid (H2CO3) and sodium bicarbon-ate (NaHCO3) This buffer system helps maintain a stable pH by soaking up excess H+ with HCO3
minus which in solution forms carbonic acid (H2CO3) Carbonic acid is a weak acid and readily dissociates to give CO2 which is transported in dissolved form to the lungs for excretion
H+ + HCO3minus harr H2CO3 harr H2O + CO2
The bicarbonate system therefore completes the neutraliza-tion of excess H+ and a stable plasma pH is maintained The relationships between pH HCO3
minus and CO2 in this system are described by the HendersonndashHasselbalch equation15
pH = 61 + log HCO3minus003 times CO2
where 61 is the log of the dissociation coefficient of carbonic acid and 003 the solubility of CO2 in plasma Buffers are most potent when there are equal amounts of H+ and HCO3
minus in solution The
2 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
bicarbonate system is not a potent buffer however as HCO3minus
and CO2 are readily altered by the body this system plays a very powerful role in pH homeostasis15
Respiratory regulationThe respiratory system adapts within minutes to hours as part of the acute response to acidosis This system modifies pH by balancing production of H+ with ventilatory clearance of CO2
H+ directly stimulates chemoreceptors in the respiratory cen-tre of the brainstem producing an increase in respiratory rate26 The response to respiratory acidosis is very rapid as CO2 easily diffuses across the bloodndashbrain barrier however in metabolic acidosis compensation is delayed until plasma bicarbonate fully equilibrates with cerebrospinal fluid (CSF) bicarbonate There is an inverse relationship between alveolar ventilation and partial pressure of dissolved carbon dioxide (PaCO2) a reduction in alveolar ventilation raises PaCO2 and decreases pH Changes in pH therefore affect alveolar ventilation and conversely changes in alveolar ventilation cause significant changes in pH
Renal regulationThe kidneys provide a delayed but sustained response to acidndashbase imbalances by excreting either acidic or alkaline urine In full-term and preterm babies the capacity for acid excretion and bicarbonate reabsorption is reduced as glomerular filtration rates are low and tubular function immature7 Renal function matures with gestation postnatal age and glucocorticoid and thyroid hormones78 Due to their limited capacity to preserve HCO3
minus newborn infants have lower serum bicarbonate levels and are predisposed to acidosis7
Bicarbonate is not effectively reabsorbed due to its size and electrical charge Instead intraluminal HCO3
minus combines with secreted H+ in tubular luminal fluid to produce carbonic acid which dissociates to give H2O and CO2 This CO2 diffuses into tubular cells combines with intracellular H2O and forms carbonic acid which liberates HCO3
minus and H+ HCO3minus is then
recovered to the circulation by exchange for chloride ions (Clminus) through the basal cell membrane247
Renal acid secretion occurs at all sites except the loop of Henle Primary active transport accounts for 5 and secondary for the remaining 95 of total H+ excretion Secondary trans-port involves an exchange between luminal Na+ and intracel-lular H+ Both ions bind to a membrane transport protein The Na+ concentration gradient between the tubular lumen and cells enables Na+ drag into the cell which generates energy to fuel active H+ excretion into the tubular lumen1ndash47
Quantifying acidosis
Standard base excess is a calculated value derived from PaCO2 and pH It is expressed as the mmollitre of base above or below normal buffer bases required to correct the pH to 74 at a PaCO2 of 40 mmHg A negative base excess or base deficit indicates an acidosis while a positive base excess indicates a relative alkalosis15
Anion gap is the measured difference between anions and cations in the blood
Anion gap = (Na+ + k+) minus (HCO3+Clminus)
paeDiatRiCS anD CHilD HealtH 184 17
Calculation of the anion gap enables clinicians better to define the underlying cause of a metabolic acidosis9 The common causes of an increased anion gap acidosis in neonates include lactic acidosis due to tissue hypoperfusion and hypoxia it may also be seen with certain inborn errors of metabolism and in uraemia910 The anion gap can help distinguish between the rela-tively benign non-anion gap hyperchloraemic acidosis seen in premature infants and a pathological lactic acidosis due to poor end-organ perfusion1011
Strong ion theory
Stewart described a complex acidndashbase model which proposed that H+ concentration results from the dissociation of water which is influenced by PaCO2 the strong ion difference and plasma weak acids12
Strong ions are ions that dissociate at normal body pH and include Na+ K+ and Clminus Weak acids in plasma which contrib-ute include albumin inorganic phosphate and plasma proteins their concentrations do not change with pH and are therefore a constant The effect of these factors and other unmeasured tissue ions on acidndashbase status can be quantified by the calculation of the strong ion gap (SIG)112 In the neonatal unit it is perhaps more important that we consider how principles of this model may relate to acidndashbase status rather than fully to quantify the SIG Theoretically low albumin and phosphate levels which fre-quently occur in premature infants by reducing the concentra-tion of weak acids can produce a relative alkalosis while high phosphate levels in renal failure may contribute to acidosis
Tissue oxygenation
Oxygenation is closely linked to acidndashbase status as optimal cel-lular function requires oxygen to fuel aerobic metabolism and produce energy In hypoxic conditions anaerobic metabolism predominates which is energy inefficient and results in a lactic acidosis1011
Tissue oxygen availability is related to regional blood flow haemoglobin level and haemoglobin oxygen affinity Arterial blood gases measure the partial pressure of dissolved oxygen (PaO2) which represents a small component of total oxygen con-tent the majority being transported bound to haemoglobin The relationship between percentage haemoglobin saturation (SaO2) and PaO2 is described by the sigmoidal oxyhaemoglobin disso-ciation curve which enables us to relate the two measures to each other235 The affinity of haemoglobin for oxygen is altered by local tissue factors Increases in temperature H+ PaCO2 and 23-diphosphoglycerate (DPG) levels shift the oxyhaemoglobin dissociation curve to the right reducing affinity for oxygen Decreases in temperature H+ PaCO2 and 23-DPG levels shift the curve to the left increasing oxygen affinity1ndash35 In the body haemoglobin oxygen affinity continuously changes increasing in the lungs to enable efficient oxygen uptake and decreasing at tissue level to provide efficient oxygen delivery to metabolically active tissues
Avoiding both hypoxia and hyperoxia is important in the neo-natal unit as deleterious effects of hypoxia are seen in infants with pulmonary hypertension1314 while hyperoxia is associated with an increased incidence of retinopathy of prematurity1516
3 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Clinical acidndashbase imbalances
Clinical acidndashbase imbalances can be respiratory metabolic or a mixture of both These abnormalities may be corrected by the acidndashbase regulatory mechanisms in the body in an attempt to maintain normal pH (Figure 1)
Respiratory acidosisThis occurs when any disorder leads to decreased alveolar ventilation Common causes of respiratory acidosis are listed in Table 1 Reduced respiratory clearance of CO2 means more dissolved CO2 accumulates in the plasma leading to increased production of carbonic acid and H+ Through chemoreceptor stimulation respiratory acidosis rapidly alters ventilation in an attempt to reduce CO226 Chemoreceptor mediated ventila-tory increases may only partly adjust in premature infants with underlying lung disease In babies with a sustained respiratory acidosis eg in chronic lung disease then metabolic compen-sation occurs through increased renal excretion of H+ and reabsorption of HCO3
minus slowly restoring pH to around 80 of normal47
paeDiatRiCS anD CHilD HealtH 184 17
The management of PaCO2 levels in infants receiving mechan-ical ventilation has important clinical implications Premature babies have impaired cerebral autoregulation17 and adverse neurological sequelae are reported in association with high PaCO2 levels18ndash20 Ventilation strategies which advocate lsquoper-missive hypercarbiarsquo have been developed to minimize airways damage from mechanical ventilation21 Published data suggest pulmonary benefits however the safe level of PaCO2 remains to be defined in premature infants2021
Respiratory alkalosisThis occurs when more CO2 is excreted than is produced by the body Pathological conditions leading to respiratory alkalosis are rare Hyperventilation in the neonatal setting is often iatrogenic or may be due to disorders in brainstem control of breathing including hypoxicndashischaemic encephalopathy or primary central nervous system abnormalities (see Table 1)
If respiratory alkalosis is sustained it may be compensated for by reduced reabsorption of filtered bicarbonate Reported adverse associations of low PaCO2 include periventricular leuco-malacia and intraventricular haemorrhage1922
K+
H+
Overventilation
CO2 + H2O harr H2CO3 harr H+ + HCO3ndash
Bicarbonate Buffer
Intracellular Buffer
uarr H+ excretionuarr HCO3
ndash absorption
uarr buffered H+
(NH4+ H2PO4
ndash)uarr ventilation rate
RespiratoryAcidosis
MetabolicAcidosis
darr CO2and uarr pH
RespiratoryAlkalosis
MetabolicAlkalosis
darr H+ anduarr pH
darr ventilation rate
uarrCO2
and darr pH
darr H+ excretiondarr HCO3
ndash absorption
uarrH+ and
darr pH
Brain
Brain
Intracellular Buffer
H+
K+
Sepsis
HypoxiaRDS
Metabolismand growth
Diuretics
Airwayobstruction
Neuromuscularproblems
IEM
Gastric losses
+ +
ndash -
Renal BufferRespiratory Buffer
Figure 1 mechanisms for regulation of extracellular pH iem inborn errors of metabolism RDS respiratory distress syndrome
4 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Common causes of acidndashbase imbalances
pH PCO2 H2CO3 Base excess Common neonatal causes
Respiratory acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
uarr normal normal bull upper airway obstruction choanal atresia
pierre-Robin sequence
bull lung abnormalities respiratory distress
syndrome transient tachypneoa of
newborn pneumonia meconium aspiration
syndrome pulmonary hypoplasia
congenital pulmonary malformations
bull Central hypoventilation hypoxic-ischaemic
encephalopathy intracranial haemorrhage
bull neuromuscular insufficiency congenital
myopathies congenital neuropathies
bull iatrogenic inadequate ventilatory settings
Compensated lower limit
of normal
uarr uarr gt+3
metabolic acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
normal darr ltminus3 increased anion gap
bull lactic acidosis sepsis hypoperfusion
shock necrotizing enterocolitis
bull inorganic acidosis inborn errors of
metabolism renal failure
normal anion gap
bull increased gastrointestinal H2Co3 losses
ileostomy diarrhoea
bull Renal tubular acidoses
Compensated lower limit
of normal
darr darr ltminus3
Respiratory alkalosis Uncompensated gt 745 darr normal normal bull iatrogenic excessive ventilatory settings
bull Compensatory hyperventilation hypoxic-
ischaemic encephalopathy
Compensated higher limit
of normal
darr darr ltminus3
metabolic alkalosis Uncompensated gt 745 normal uarr gt+3 bull gastric losses vomiting non-replacement
of excessive nasogastric aspirates
bull thiazide and loop diuretics
bull Hypokalaemia
Compensated higher limit
of normal
uarr uarr gt+3
Table 1
Metabolic acidosisThis frequently affects infants in the neonatal unit and has many causes1011 (see Table 1) There may be overproduction of tissue acid impaired acid clearance gastrointestinal loss of bicarbonate or an exogenous increased acid load eg chloride total paren-teral nutrition (TPN) or albumin1ndash323
Calculation of the anion gap to distinguish an increased anion gap acidosis from a non-anion gap acidosis is important both for treatment and prognosis1011 Acidosis stimulates respiratory compensation but this is limited in unstable infants Similarly renal compensation with improved HCO3
minus conservation is con-strained by tubular immaturity Treatment of the acidosis should be directed at the underlying cause eg hypoxia hypotension or excess Clminus rather than by administration of base
Metabolic alkalosisThis is unusual in neonates and is most frequently seen in infants with chronic lung disease or heart failure who are receiving diuretics Diuretics cause alkalosis by increasing renal fluid and Na+ losses An active process to reabsorb Na+ occurs in tubule cells which through enhanced H+ secretion and HCO3
minus reab-sorption produce alkalosis27
paeDiatRiCS anD CHilD HealtH 184 17
Metabolic alkalosis may also occur with excessive loss of gas-tric contents eg protracted vomiting or inadequate replacement of nasogastric aspirates (see Table 1)
Interpreting blood gases
Blood gas measurements can provide important diagnostic and prognostic information and a systematic approach to blood gas analysis is described in Table 2 The clinical management of infants with abnormal gases requires a good understanding of acidndashbase physiology and tissue oxygenation and an apprecia-tion of factors which may affect the reliability of samples
Arterial blood sampling is the gold standard however indwelling arterial catheters and arterial stab samples are usually restricted to infants who are critically ill or those who require sig-nificant ongoing intervention Gases are most frequently measured in capillary or venous samples which correlate well with arterial samples for PaCO2 pH and base excess in babies and children receiving intensive care These correlations however are not valid in infants with peripheral vasoconstriction and hypotension2324
Non-invasive monitoring techniques may enable us to reduce the frequency of blood gas sampling Transcutaneous monitoring
5 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
A systematic approach to blood gas analysis
1 Collect the relevant information
bull type of gas ndash capillary or arterial
bull Current respiratory support ndash document level
bull transcutaneous Co2 and Sao2 levels
bull Clarify no significant clinical events before sampling
2 pH accept a range between 730 and 745 in newborn
babies this is lower than in older children is there an
alkalosis (pH gt 745) or an acidosis (lt 730)
3 Co2 aim for a range between 45 and 65 kpa a paCo2 level
more than 65 kpa suggests inadequate alveolar ventilation
while less than 45 kpa suggests hyperventilation Correlate
values with non-invasive measures
4 o2 Can only be assessed from arterial gases aim for pao2
between 60 and 80 kpa Correlate results with pulse
oximetry levels
5 HCo3 and base excess normal HCo3 level is between 20 and
24 mmollitre and bases excess +3 to minus3
6 anion gap look at the anion gap and lactate to help identify
the cause of an acidosis normal lactate levels should be less
than 2 mmollitre
7 Respiratory or metabolic compensation look at the pH and
assess whether it is appropriate for the Co2 level or is there
evidence of compensation
8 interpret use both the clinical history and blood gas
findings to help you identify the primary problem aim your
management at treating the underlying cause
9 Reassess if clinical management changes have been made
repeat the blood gas after an appropriate time interval to
ensure improvement
Table 2
provides a highly accurate and reliable method for measuring PaCO2 through the skin it can however be technically difficult may cause tissue damage and is of limited reliability when peripheral perfusion is reduced25 Continuous end-tidal CO2 measurements correlate well with arterial CO2 values in patients with normal ventilation and perfusion however in babies with lung disease alveolar collapse small tidal volumes and rapid respiratory rates can make these measurements unreliable26 Despite its limitations transcutaneous monitoring provides the best method for CO2 trend monitoring in the neonatal intensive care unit (NICU)25
Oxygen saturation levels can be continuously measured non-invasively using pulse oximetry While oximetry is easy to perform and accurate on occasion SaO2 levels obtained may be unreliable when tissue perfusion is poor or with movement artefact SaO2 monitoring is highly sensitive at detecting hypoxia but is limited in detecting hyperoxia as at levels more than 90 small changes in SaO2 may result in unacceptably large increases in PaO227 It is therefore essential that SaO2 alarm limits are set for all neonates receiving respiratory support to detect hypoxia and prevent hyperoxia1627
Continuous non-invasive monitoring provides invaluable information when managing complex infants in the NICU but it does not replace the need for regular blood gas analysis
paeDiatRiCS anD CHilD HealtH 184 17
ReFeRenCeS
1 Kellum Ja Determinants of blood pH in health and disease
Crit Care 2000 4 6ndash14
2 Quigley R Baum m neonatal acid base balance and disturbances
Semin Perinatol 2004 28 97ndash102
3 Brouillette Rt Waxman DH evaluation of the newbornrsquos blood gas
status Clin Chem 1997 43 215ndash221
4 Chan JC acid-base disorders and the kidney Adv Pediatr 1983 30
401ndash471
5 Siggaard-andersen o the pH-log pCo2 blood acidndashbase nomogram
revised Scand J Lab Invest 1962 14 598ndash604
6 Saetta m mortola Jp interaction of hypoxic and hypercapnic stimuli
on breathing pattern in the newborn rat J Appl Physiol 1987 62
506ndash512
7 Baum m Quigley R postnatal renal development in Seldin DW
giebisch g eds the kidney physiology and pathophysiology new
york lippincott Williams and Wilkins 2000 p 703ndash726
8 ortiz la Quan a Weinberg a et al effect of prenatal
dexamethasone on rat renal development Kidney Int 2001 59
1663ndash1669
9 gabow pa Kaehny WD Fennessey pV goodman Si gross pa
Schrier RW Diagnostic importance of an increased serum anion gap
N Engl J Med 1980 303 854ndash858
10 lorenz Jm Kleinman li markarian K oliver m Fernandez J Serum
anion gap in the differential diagnosis of metabolic acidosis in
critically ill newborns J Pediatr 1999 135 751ndash755
11 Deshpande Sa platt mp association between blood lactate and
acid-base status and mortality in ventilated babies Arch Dis Child
1997 76 F15ndash20
12 Stewart pa modern quantitative acid-base chemistry Can J Physiol
Pharmacol 1983 61 1444ndash1461
13 Dakshinamurti S pathophysiologic mechanisms of persistent
pulmonary hypertension of the newborn Pediatr Pulmonol 2005
39 492ndash503
14 mourani pm ivy DD gao D abman SH pulmonary vascular
effects of inhaled nitric oxide and oxygen tension in
bronchopulmonary dysplasia Am J Respir Crit Care Med 2004
170 1006ndash1013
15 Deulofeut R Critz a adams-Chapman i Sola a avoiding hyperoxia
in infants le 1250 g is associated with improved short- and long-
term outcomes J Perinatol 2006 26 700ndash705
16 Chow lC Wright KW Sola a Can changes in clinical practice
decrease the incidence of severe retinopathy of prematurity in very
low birth weight infants Pediatrics 2003 111 339ndash345
17 Boylan gB young K panerai RB Rennie Jm evans DH Dynamic
cerebral autoregulation in sick newborn infants Pediatr Res 2000
48 12ndash17
18 Kaiser JR gauss CH pont mm Williams DK Hypercapnia during
the first 3 days of life is associated with severe intraventricular
hemorrhage in very low birth weight infants J Perinatol 2006 26
279ndash285
19 Fabres J Carlo Wa phillips V Howard g ambalavanan n Both
extremes of arterial carbon dioxide pressure and the magnitude of
fluctuations in arterial carbon dioxide pressure are associated with
severe intraventricular hemorrhage in preterm infants Pediatrics
2007 119 299ndash305
20 thome uH Carroll W Wu tJ et al outcome of extremely preterm
infants randomized at birth to different paCo2 targets during the
first seven days of life Biol Neonate 2006 90 218ndash225
6 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
21 Carlo Wa Stark aR Wright ll et al minimal ventilation to prevent
bronchopulmonary dysplasia in extremely-low-birth-weight infants
J Pediatr 2002 141 370ndash374
22 okumura a Hayakawa F Kato t et al Hypocarbia in preterm
infants with periventricular leukomalacia the relation between
hypocarbia and mechanical ventilation Pediatrics 2001 107
469ndash475
23 peters o Ryan S matthew l Cheng K lunn J Randomised
controlled trial of acetate in preterm neonates receiving parenteral
nutrition Arch Dis Child 1997 77 F12ndash15
24 yildizda D yapiciolu H yilmaz Hl Sertdemir y Correlation of
simultaneously obtained capillary venous and arterial blood gases
of patients in a paediatric intensive care unit Arch Dis Child 2004
89 176ndash180
25 aliwalas ll noble l nesbitt K et al agreement of carbon
dioxide levels measured by arterial transcutaneous and end tidal
methods in preterm infants 28 weeks gestation J Perinatol 2005
25 26ndash29
26 Hagerty JJ Kleinman me Zurakowski D et al accuracy of a new
low-flow sidestream capnography technology in newborns a pilot
study J Perinatol 2002 22 219ndash225
paeDiatRiCS anD CHilD HealtH 184 17
27 poets CF Wilken m Seidenberg J Southall Dp von der Hardt H
Reliability of a pulse oximeter in the detection of hyperoxemia
J Pediatr 1993 122 87ndash90
Practice points
bull a stable extracellular pH is important for optimal cellular
functioning
bull abnormalities in acidndashbase balance are regulated by buffer
systems and the respiratory and renal tract
bull maintaining a stable pH is challenging for newborn babies
due to their high rates of acid production and immature
regulatory mechanisms
bull arterial or capillary blood gases provide an effective way to
monitor acidndashbase balance in newborns
bull Blood gases should be analysed in a structured manner
assessing pH and then respiratory and metabolic components
bull the treatment of acidndashbase abnormalities should be directed
at the underlying problem not merely at correcting pH
7 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Recognition and management of neonatal seizuresmalcolm levene
AbstractSeizures are the most common major manifestation of central nervous
system dysfunction in the newborn there are many causes but perina-
tal asphyxia and haemorrhagicinfarction lesions account for about 75
there is now considerable evidence that frequent but short seizures in
the neonate affect subsequent neurodevelopmental outcome Studies
using eeg or modified continuous tracing of eeg activity (aeeg or CFm)
have shown that there is often electroconvulsive dissociation this re-
fers to poor correlation between electrical seizures and clinical seizures
Commonly used anticonvulsants appear to increase electroconvulsive
dissociation effective management of neonatal seizures has proved very
disappointing and less than 50 of seizures are abolished by first-line
anticonvulsant medication (phenobarbitone or phenytoin) Drugs such
as midazolam and lidocaine may further reduce seizures but require
more evaluation the challenge is to assess new and more effective anti-
convulsants which are themselves associated with little neurotoxicity
Keywords antiepileptic drugs eeg neonatal seizures neurodegeneration
Convulsions are the most common major neurological sign seen in newborn infants and their incidence estimated from large population studies is 26 per 1000 live births1 Premature infants are over four times more likely to have convulsions than full-term infants12 Neonatal status epilepticus (continuous seizure activity lasting 30 min or more) diagnosed clinically is rare and accounts for only 5 of infants with seizures1 although this is now recognized more frequently as the result of continuous EEG monitoring3
Neonatal convulsions are described as presenting in a num-ber of different ways and various seizure types can be seen in the same baby over a number of hours The frequencies of the various patterns of seizure activity are given in Table 1 In very premature babies and to a lesser extent in term infants minor movement abnormalities may be difficult to identify as subtle seizures These include lip smacking tongue thrusting mouth-ing pedalling type movements of the lower limbs or swimming movements of the arms Apnoea can be a common manifesta-tion of subtle seizures The signs can be protean and vary from baby to baby or even in the same baby Virtually any stereotypic
Malcolm Levene MD FMedSc FRCPCH FRCH is Professor and Head of
Department of Paediatrics and Child Health at University of Leeds Leeds
and Honorary Neonatologist at Leeds General Infirmary Leeds UK
paeDiatRiCS anD CHilD HealtH 184 178
movement may be a manifestation of a seizure disorder in the newborn
Aetiology
The more carefully the fitting baby is investigated the more likely it is that a cause for the seizures will be found A number of recent papers have described the aetiology of neonatal con-vulsions after extensive investigations14 Tekgul et al4 recently studied a consecutive group of full-term infants with evidence of neonatal convulsions (recognized both clinically and on EEG) and reported their outcome Table 2 summarizes these data as well as risk of moderate or severe disability for each causative factor Perinatal asphyxia is the commonest cause for convul-sions in term infants with haemorrhagic or ischaemic lesions also being common
Overall the prognosis for the group of term babies with con-vulsions was good 72 had a favourable outcome Where asphyxia (hypoxicndashischaemic insult) is the cause of neonatal convulsions the outcome is poor in 50 The prognosis for neonatal convulsions when they were due to arterial or cere-brovenous infarction or intracranial haemorrhage was generally good Individually inborn errors are a very rare cause of neo-natal convulsions but in view of the treatable nature of some of these it is essential that these be considered and investigated appropriately5
Patterns of seizure activity in the newborn
Movement pattern Frequency ()
Clonic 50
tonic 20
Subtle 10ndash35 depending on maturity
myoclonic 5
Table 1
Cause incidence and outcome of neonatal convulsions in term infants14
Aetiological factor Incidence () Poor outcome ()
asphyxia 38ndash40 50
Cerebral arteriovenous
infarction
20 0
intracranial haemorrhage 12ndash20 13
Congenital cerebral anomaly 5ndash10 100
Hypoglycaemiahypocalcaemia 3ndash19
infection 3ndash20
inborn error of metabolism 1
unknown cause 10ndash13 0
Refers to moderate and severe neurodevelopmental abnormalitynumbers too small to make meaningful predictions
Table 2
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Controversies in the clinical management of neonatal seizures
In recent years we have learnt much more about the neurobi-ology of seizures and their effect on the developing brain The neonatal brain is in a neurophysiologically hyperexcitable state compared to the more mature brain and therefore is more prone to seizure activity This is due largely to a relative excess of GABA neuroreceptors GABA receptors are usually inhibitory but in the immature brain they have a paradoxically excitatory effect This changes at about term in primates and with progressive develop-ment they adopt a neuroinhibitory role6
The propensity to seizures in the neonatal brain makes resolv-ing the balance of risks between continuing seizure activity on the one hand against potentially adverse effects of therapy on the other a very important equation Added to this is the problem of accurately diagnosing neonatal seizures and whether commonly used anticonvulsants are successful in controlling them
These conundrums can be posed as a series of challenging questions which are discussed below
Do neonatal convulsions cause brain injuryConvulsions are a sign of neurological compromise and may indi-cate significant underlying structural brain damage or biochemi-cal disturbance which may cause further brain damage in its own right There has been considerable debate about the scale of the disability that convulsions cause the immature brain over and above that due to the underlying cause Most of our knowledge comes from studies in rodents and these have provided some tentative answers to this question
Seizures in the mature brain lead to neuronal necrosis but studies in very young rat pups whose brain development is somewhat similar to full-term infants have shown that a series of five brief seizures on five successive days does not cause struc-tural neuronal damage but does produce morphological changes in hippocampal neurones and worryingly deficits in the rat learning and visual spatial memory function in adolescent and adult life7 A single prolonged neonatal convulsion in similarly immature rats does not produce any functional effects8 Others have shown that following priming of the neonatal rat brain by short seizures as described above a further insult comprising induction of status epilepticus in the same rats at an older age causes neuronal necrosis9 This has been referred to as the lsquotwo hit hypothesisrsquo10
A more specific question is does seizure activity in an already significantly compromised brain cause additional neuropathol-ogy Wirrell et al11 studied a series of immature rat pups with the induction of an hypoxicndashischaemic (asphyxial) insult fol-lowed by either chemically-induced fits or a control sham pro-cedure In the more severely asphyxiated animals the degree of brain damage was increased significantly in those that had the additional burden of induced seizures
In summary these studies show that the immature brain is more resistant to short frequent post-seizure damage than the mature brain but despite resulting in no loss of neuronal numbers the function of the brain is permanently affected in later life In the asphyxiated brain seizures appear to have an additional adverse effect on brain damage Furthermore the immature brain that has been lsquoprimedrsquo by early seizures is more
paeDiatRiCS anD CHilD HealtH 184 179
vulnerable to status epilepticus later in life It would appear from these data that frequent seizures in the human infant should be stopped and this begs the question as to whether currently used anticonvulsants effectively control neonatal seizures
Can we rely on clinical versus EEG diagnosis of neonatal convulsionsTraditionally the diagnosis of neonatal convulsions has been made by observation and description of the frequency of abnor-mal movements EEG has been technically difficult in the hostile electrical activity of a neonatal intensive care environment and considerable expertise is required for analysis of the trace It is usually not practical to undertake traditional EEG recordings at the time the baby shows abnormal movements More recently various technological developments have allowed more direct investigation of neuronal electrical activity by either video-EEG or compressed recording of the amplitude integrated EEG (aEEG or CFM)
Rennie et al3 at Kingrsquos College Hospital London have under-taken extensive evaluation of video-EEG and have found that this technique detects many convulsions not recognized by a single channel aEEG or CFM trace Of 19 infants with evidence of convulsions on EEG only four were recognized on CFM but this may have been due to the observersrsquo lack of experi-ence with this technique In other centres that have developed appropriate expertise aEEG or CFM has proved more sensitive to the detection of seizures Video-EEG studies have also shown that many movements interpreted by experienced clinicians to be seizures are not associated with abnormal cortical activity Conversely many electrical seizures are not associated with abnormal movements This is referred to as electroconvulsive dissociation
In summary clinical observation alone to detect the fitting baby is unreliable in that it may either over-detect seizure activ-ity which is not present on EEG or under-detect clinical seizures in infants with EEG-proven convulsions The decision as to which babies to treat with antiepileptic drugs therefore becomes somewhat arbitrary
Do anticonvulsants stop neonatal seizuresAlthough neonatal seizures are common there are few random-ized controlled trials assessing the benefits of antiepileptic drugs (AEDs) in the treatment of this condition Phenobarbitone is the most widely used first-line AED and in an Australasian study 95 of neonatologists and paediatric neurologists used this drug as first-line management12 The most commonly used loading dosage is 20 mgkg but regimens of up to 40 mgkg have been recommended (Table 3)13 Four trials have evaluated the effect of phenobarbitone in abolishing neonatal seizures Two of these studies used EEG to monitor response to the drug1415 and one compared phenobarbitone with phenytoin15 In the latter study seizures were completely controlled in only 43 of babies and in the group where phenytoin was the first drug used com-plete seizure control was achieved in 45 This study switched babies from their first AED to the other if complete control was not obtained on EEG monitoring after exposure to first-line therapy In babies who had been given phenobarbitone as first-line therapy seizure control was only achieved in 57 after phenytoin was added In those given phenytoin first complete
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Dosage regimens for first- second- and third-line anticonvulsants in the neonatal period
Loading dose Second loading dose if first
unsuccessfulMaintenance dose
phenobarbitone 20 mgkg by slow iv injection 10 mgkg iv 25ndash5 mgkg od
phenytoin 20 mgkg iv over 20 min not recommended
midazolam 150ndash200 μgkg iv infusion 1 μgkgmin iv infusion increasing to 5 μgkgmin
until favourable response
lidocaine 2 mgkg iv over 10 min 6 mgkgh for 6 h iv then 4 mgkgh for 12 h then
2 mgkgh for 12 h
lorazepam 005ndash01 mgkg by slow iv injection
Diazepam 03ndash04 mgkg iv over 3ndash5 min
lidocaine should not be used if the infant has previously been treated with phenytoin
Table 3
seizure control was achieved with the adding of phenobarbitone in 62
Boylan et al14 assessed the efficacy of phenobarbitone (20ndash40 mgkg iv over 20 min) in 14 babies monitored by video-EEG in only four was there complete abolition of seizures and in the other 10 electroconvulsive seizure activity increased whereas clinical evidence of seizures reduced This has been termed elec-troclinical dissociation and anticonvulsant drug use in the new-born appears to increase this feature They also showed that the babies least likely to respond to the first-line AED are those with the most abnormal background EEG
Two studies have evaluated the use of phenobarbitone in babies who had sustained significant asphyxial insult at birth Hall et al13 compared high-dose phenobarbitone (mean 39 mgkg) versus standard dose (27 mgkg) and reported fewer convul-sions and a significant reduction of severe disability or death in the high dose group (RR 030 CI 010ndash093) A recent study from India16 of babies with hypoxicndashischaemic encephalopathy ran-domized 25 babies to phenobarbitone (20 mgkg loading dose) and compared them with 20 control babies Only 2 of 25 (4) in the phenobarbitone group developed convulsions compared with 8 of 20 (40) in the control group (p = 001) Because of the specific enrolment criteria (asphyxial insult) neither of these studies is strictly comparable to the studies by Painter et al15 and Boylan et al14 whose intention was to assess the efficacy of first-line anticonvulsant therapy on convulsions of any cause diagnosed either clinically or by EEG
Other anticonvulsants used as second- and third-line drugs have been subject to few studies in the newborn Midazolam is administered as a bolus followed by continuous infusion A recent study17 has shown that in 10 of 13 neonates given intravenous midazolam for status epilepticus control of electri-cal seizures was achieved within the first hour of treatment having been previously shown to be refractory to phenobarbi-tone treatment Some of these babies required a second bolus infusion of midazolam to obtain control of all electrographic seizures
In some parts of Europe lidocaine is used as a third-line anti-convulsant Malingre et al18 evaluated 20 infants refractory to
paeDiatRiCS anD CHilD HealtH 184 180
both phenobarbitone and midazolam and who were then given lidocaine by continuous infusion Lidocaine was effective in abolishing electroconvulsive seizures diagnosed by aEEG in 76 of the treatment courses studied No babies developed cardiac arrhythmias a previously reported complication of lidocaine in older patients As a result of pharmacokinetic studies the dosage regimen has been modified (see Table 3)
In summary phenobarbitone is effective in seizure control in less than 50 of babies and even when combined with phe-nytoin the efficacy of these drugs together remains poor More worrying is the observation that phenobarbitone tends to reduce clinically evident seizures thereby giving the clinician a false sense of security whilst having little or no effect on the num-bers of electroconvulsive disorders This has been summarized appropriately as lsquoafter all these years we still love what doesnrsquot workrsquo19 Both midazolam and lidocaine infusions appear to be effective in abolishing severe seizures in some infants resistant to phenobarbitone Lidocaine should not be given to babies previ-ously exposed to phenytoin for fear of a synergistic adverse effect on cardiac rhythm
Do antiepileptic drugs cause brain damageA riskndashbenefit analysis is needed to evaluate the efficacy of anticonvulsants in stopping neonatal seizures which is poor with standard anticonvulsants as discussed above against the risk of administering the anticonvulsant drugs themselves Phenobarbitone has been reported to have adverse effects on the developing brain including inhibition of brain growth20 neuronal toxicity21 and adverse behavioural and cognitive effects into adult life when administered to young animals22 Phenytoin shows unpredictable plasma levels and potential cardiotoxicity
Recent studies have shown an effect of AED exposure on the developing brain by causing neurodegeneration23 Phenytoin administration to immature rat pups at doses which produce serum levels similar to those achieved in human neonates was associated with widespread neuronal death as a result of apop-tosis (programmed cell death) Phenobarbitone had a similar effect when a dosage regimen similar to 40 mgkg was used and
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
this effect was maximal in the more immature brain Diazepam and clonazepam also resulted in a similar effect Midazolam and lidocaine were not tested in this study The combination of phenobarbitone or phenytoin with diazepam had a particularly profound effect on neurodegeneration
In summary recent data suggest that the commonly used AEDs for neonatal convulsions may in themselves cause neuro-degeneration due to apoptosis with lasting effects on develop-ment Many babies with neonatal convulsions are treated with at least two AEDs and this may produce more severe adverse effects than the seizures themselves
Practical management of neonatal seizures
Assimilation of these data and formulation of a rational policy is difficult when faced with a fitting neonate on an intensive care unit and pressure on the medical staff to lsquodo somethingrsquo but it is important to accept that sometimes doing nothing is preferable to using potentially dangerous drugs in a situation which does not warrant such intervention Many babies who have normal interseizure neurological clinical findings and whose seizures are relatively brief and infrequent probably do not need anticon-vulsant medication A normal or near-normal background EEG trace should reassure the clinician that anticonvulsants can be withheld
Some causes of neonatal convulsions are treatable such as meningitis hypoglycaemia hypocalcaemia and inborn errors of metabolism and each baby should be rapidly and carefully investigated for cause of the convulsions
In some babies clinical assessment of seizures is difficult ie when the baby is very sick small or paralyzed Sometimes it may be difficult to assess the significance of certain movement pat-terns Under these circumstances an EEG may prove to be very helpful In many units EEG is not available out of hours and a simple aEEG or CFM is strongly advised Modern instruments are very simple to apply and prolonged or frequent seizures should be identified with only moderate training The printout can be faxed to a more senior doctor if there is doubt as to what is shown on the trace
The balance of knowledge now is that frequent seizures cause additional damage to the developing brain and that treatment to abolish the seizures is warranted Unfortunately there is little evidence that the majority of seizures can be effectively termi-nated by current standard therapy Furthermore it appears that the more abnormal the background EEG the more difficult it is to control the seizures Nevertheless a written protocol for the management of neonatal convulsions is required on each unit Phenobarbitone and phenytoin remain the mainstay of treat-ment although their effectiveness is disappointing There is little to suggest that midazolam is more effective than lidocaine as third-line therapy but lidocaine is precluded if phenytoin has been previously used
In view of the anxiety as to the neurodegenerative effects on the immature brain of most anticonvulsants used in the neonatal period (particularly when multiple drugs are used) it is prefer-able to use only one drug to maximum dosage before introduc-ing a second In addition the duration of anticonvulsants should be minimized and the drugs stopped at the earliest opportu-nity It is my practice to stop anticonvulsants prior to discharge
paeDiatRiCS anD CHilD HealtH 184 18
from hospital if the baby is neurologically normal on clinical examination
REFEREnCES
1 Ronen gm penney S andrews W the epidemiology of clinical
neonatal seizures in newfoundland a population-based study
J Pediatr 1999 134 71ndash75
2 lanska mJ lanska DJ Baumann RJ et al a population-based study
of neonatal seizures in Fayette County Kentucky Neurology 1995
45 724ndash732
3 Rennie Jm Chorley g Boylan gB et al non-expert use of the
cerebral function monitor for neonatal seizure detection Arch Dis
Child Fetal Neonatal Ed 2004 89 F37ndashF40
4 tekgul H gauvreau K Soul J et al the current etoliologic profile
and neurodevelopmental outcome of seizures in term newborn
infants Pediatrics 2006 117 1270ndash1280
5 Surtees R Wolf n treatable neonatal epilepsy Arch Dis Child 2007
92 659ndash661
6 Ben-ari y Holmes gl effects of seizures on developmental
processes in the immature brain Lancet Neurol 2006 5 1055ndash
1063
7 Holmes gl gairsa Jl Chevassus-au-louis n et al Consequences of
neonatal seizures in the rat morphological and behavioral effects
Ann Neurol 1998 44 845ndash857
8 Stafstrom Ce Chronopoulos a thurber S et al age-dependent
cognitive and behavioural deficits following kainic-acid inducing
seizures Epilepsia 1993 34 420ndash432
9 Schmid R tandon p Stafstrom Ce et al effects of neonatal seizures
on subsequent seizure-induced brain injury Neurology 1999 53
1754ndash1761
10 Hoffmann aF Zhao Q Holmes gl Cognitive impairment following
status epilepticus and recurrent seizures during early development
support for the ldquotwo-hit hypothesisrdquo Epilepsy Behav 2004 5
873ndash877
11 Wirrell eC armstrong ea osman lD et al prolonged seizures
exacerbate perinatal hypoxic-ischemic brain damage Pediatr Res
2001 50 445ndash454
12 Carmo KB Barr p Drug treatment of neonatal seizures by
neonatologists and paediatric neurologists J Paediatr Child Health
2005 41 313ndash316
13 Hall Rt Hall FK Daily DK High-dose phenobarbital therapy in term
newborn infants with severe perinatal asphyxia a randomized
prospective study with three-year follow-up J Pediatr 1998 132
345ndash348
14 Boylan gB Rennie Jm pressler Rm et al phenobarbitone neonatal
seizures and video-eeg Arch Dis Child Fetal Neonatal Ed 2002 86
F165ndash170
15 painter mJ Scher mS Stein aD et al phenobarbital compared with
phenytoin for the treatment of neonatal seizures N Engl J Med
1999 341 485ndash489
16 Singh D Kumar p narang a a randomized controlled trial of
phenobarbital in neonates with hypoxic ischemic encephalopathy
J Matern Fetal Neonatal Med 2005 18 391ndash395
17 Castro Conde JR Borges H Domenech martinez e et al midazolam
in neonatal seizures with no response to phenobarbital Neurology
2005 64 876ndash879
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
18 malingre mm Van Rooij lgm Rademaker Cma et al Development
of an optimal lidocaine infusion strategy for neonatal seizures Eur
J Pediatr 2006 165 598ndash604
19 Sankar R painter mJ neonatal seizures after all these years we still
love what doesnrsquot work Neurology 2005 64 776ndash777
20 Diaz J Schain J Bailey Bg phenobarbital-induced brain growth
retardation in artificially reared rat pups Biol Neonate 1977 32 77ndash82
21 mattson RH phenobarbital toxicity in levy RH Dreifuss Fe
mattson RH et al eds antiepipeptic Drugs 3rd edn new york
Raven 1985 p 341ndash355
22 mikati ma Holmes gl Chronopoulos a et al phenobarbital
modifies seizure-related brain injury in the developing brain Ann
Neurol 1994 36 425ndash453
23 Bittigau p Sifringer m genz K et al antiepileptic drugs and
apoptotic neurodegeneration in the developing brain Proc Natl
Acad Sci U S A 2002 99 15089ndash15094
paeDiatRiCS anD CHilD HealtH 184 182
Practice points
bull the clinician needs to be aware that almost any repetitive
stereotype movement pattern can be a manifestation of
neonatal seizures
bull eeg is important in defining neonatal seizures
bull Frequent short-lived seizures have been shown to cause long-
term neurodevelopmental problems
bull Conventional anticonvulsant medication is ineffective in
abolishing neonatal seizures in greater than 50 of cases
bull there is evidence that exposure of the neonatal brain to
multiple anticonvulsants causes neuronal death
bull Future research is needed to evaluate more effective
anticonvulsants for treating this condition
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
Emotional support for families of sick neonatesMarina nicolaou
cristine Glazebrook
AbstractParents of sick neonates experience high levels of stress anxiety and
depression Most interventions with families of sick infants have focused
on fostering the motherndashinfant relationship through the provision of
information about infant developmental needs or through increased
motherndashinfant contact Many of these studies have reported improved
maternal well-being though there are some concerns about the scope
and practicality of large-scale interventions The few studies to have
prioritized emotional support for parents of sick neonates have pro-
duced encouraging results even interventions requiring relatively few re-
sources such as telephone support parent-to-parent support and group
support have been associated with reduced psychological morbidity for
parents The needs of parents can change throughout their infantrsquos hos-
pitalization and not all want or benefit from the provision of additional
support Thus neonatal intensive care units should aim to provide a
varied flexible and sustainable programme of support options Further
research should focus on the needs of fathers
Keywords mental health neonatal intensive care parents
The admission of an infant to neonatal care is acknowledged to be a source of considerable distress for families This review aims to explore evidence for the psychological impact on families of having an infant in neonatal intensive care and to identify evi-dence for the effectiveness of interventions to promote parental well-being It will conclude with recommendations for strategies to support parents of vulnerable infants and suggestions for fur-ther research
Psychological impact of neonatal care for parents
The majority of research examining the effect on parents of having a sick neonate has focused on families of premature or low birthweight infants Such research has found that parents with a sick neonate exhibit high levels of stress compared to normative samples and to parents of healthy full-term infants1 Singer et al2 examined the stress experienced by mothers of high-risk very low birthweight (VLBW) low-risk VLBW and term
Marina Nicolaou MPhil is a Teaching Assistant at the School of
Community Health Sciences University of Nottingham Nottingham UK
Cristine Glazebrook PhD is a Professor of Health Psychology at the School
of Community Health Sciences University of Nottingham Nottingham UK
PaeDiaTrics anD cHilD HealTH 184 196
infants Several self-report measures were used including the Brief Symptom Inventory the Parenting Stress Index (PSI) the Impact on Family Scale and the Family Inventory of Life Events and Changes (FILE) Mothers of VLBW infants had more psycho-logical distress at 1 month compared to mothers of term infants Mothers of high-risk VLBW infants also reported high psycho-logical distress at 2 years and high levels of parenting stress at 3 years Mothers have also been found to have higher stress levels compared to fathers Shaw et al3 examined the prevalence of acute stress disorder (ASD) in 40 parents whose infants were in the neonatal intensive care unit (NICU) Nearly half of the moth-ers (44) met the criteria for ASD although none of the fathers did Furthermore the severity of the symptoms (measured by the number of concurrent symptoms) was greater for the moth-ers than for the fathers3 The reasons behind this difference have been widely speculated with some believing that it is due to the mothersrsquo greater psychological involvement with the infant as evidenced by their general greater vulnerability to postpartum psychological disorder It could also reflect gender differences in coping style
Having an infant who requires intensive medical care repre-sents a significant emotional burden for families Not only is there extreme anxiety surrounding the infantrsquos health and distress for the childrsquos suffering there is also the unfamiliar and intimidating environment of the NICU to adjust to Hopper in her review of the literature identified sources of stress for parents of sick neo-nates as falling into three areas4 Situational factors included the severity of the infantrsquos illness and how parents adapted to the life crisis of having a sick infant Personal factors involved parental emotions about their roles and the instrumental and informa-tional support which were available to them The third area was classified as environmental sources of stress and included the environment of the NICU and the relationship between parents and members of staff This relationship has been examined by several studies in the nursing literature nurses are seen as ide-ally placed to provide the necessary support and information to parents with sick neonates However whilst some studies have shown that supportive and helpful hospital staff can have a posi-tive effect on parents other studies have highlighted the prob-lems and difficulties which can manifest It has been shown that parents and nurses often have very different ideas about issues eg the necessary skills and competencies needed in an NICU or the characteristics that make a lsquogood motherrsquo
Research has shown that there may be a relationship between high levels of parental stress and an increased likelihood of depression5 Postpartum depression is a psychiatric illness which appears in 10ndash15 of postpartum women Its reported preva-lence rates however have ranged from less than 10 up to 306 depending on the instruments used the population exam-ined and the timing of the research Several factors have been found to be associated with postpartum depression including poor social support and infant-related stressors6 Evidence indi-cates that postnatal depression may be underreported and this is of concern since the mental and psychological health of the mother can affect her relationship with her infant and thus the infantrsquos cognitive and emotional development5 Depressed moth-ers appear to look touch and talk to their infants less frequently and also appear to show fewer positive and more negative faces7 The vocalizations of mothers suffering with depression have also
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
been found to be less effective at promoting cognitive growth and learning in infants8
If researchers are interested in finding ways of providing sup-port for families of sick neonates then they must listen to what such families perceive their needs to be in order to avoid increas-ing anxiety and distress Furthermore the provision of appropri-ate support be it emotional informational or social will enhance parental coping abilities increase self-esteem and reduce anxiety It should be noted though that the research conducted around these issues has often taken lsquosupport needsrsquo as being synony-mous with lsquoinformation needsrsquo Such studies have examined the type the amount and quality of information that parents receive and perceive themselves as needing but have not explored in equal depth the perceived emotional support needs of families who have a sick infant In addition the needs of parents may change throughout their infantrsquos illness Ward examined the per-ceived needs of 52 parents of infants in an NICU9 Parents rated the needs of their hospitalized infant as most important along with the need to be reassured Interestingly they ranked their support needs as least important This research was conducted during the first week of the infantsrsquo hospitalization however which would explain the preoccupation of the parents with the infantrsquos health These results demonstrate that if researchers want to find ways of providing emotional support to parents of sick neonates they must be prepared not only to listen to parents but also to be flexible enough to satisfy the parentsrsquo changing needs and expectations
Interventions aimed at supporting parents
Most interventions that been evaluated in controlled studies have focused on supporting the motherndashinfant relationship and provid-ing information on infant development Many of these interven-tions have included the aim of improving the parental emotional state and thus psychological outcomes such as stress or anxi-ety have been assessed However few studies appear to include fathers This means that strategies implemented to provide emo-tional support to families of sick neonates are often derived from interventions tailored for mothers even though fathers may have different emotional needs
A wide range of interventions with mothers and infants has been evaluated in the NICU Increasing motherndashinfant contact through kangaroo care has been found to reduce maternal anxiety1011 and educational programmes delivered to fami-lies in the NICU have also been associated with reduced emo-tional difficulties in parents12ndash14 Kaaresen and colleagues implemented an intervention which consisted of eight sessions before discharge and four home visits all by trained nurses The sample included 71 premature infants in the intervention group 69 premature infants in the control group and 74 infants in the full-term control group The randomized controlled trial found that the intervention reduced parenting stress in both mothers and fathers of premature infants compared to controls to a level equivalent to parents in the term control group13 At 6 months corrected age mothers of preterm infants who had not received the intervention had total PSI scores which were 17 points higher than the mothers of infants born at term (an effect size of 057) A similar study evaluated the efficacy of an educationalndashbehavioural programmendashCreating Opportunities for
PaeDiaTrics anD cHilD HealTH 184 19
Parent Empowerment (COPE) ndash through a randomized controlled trial with 260 families of premature infants14 COPE was a four-phase educationalndashbehavioural programme which began as early as 2ndash4 d after mothers had given birth and continued until 1 week after discharge from the NICU The programme consisted of audiotaped and written infant behaviour information along with photographs which focused on common behaviours and characteristics of premature infants It also included various par-ent activities in the form of a four-phase workbook which aimed to assist mothers in the implementation of the experimental infor-mation COPE was found significantly to reduce maternal stress in the NICU as well as maternal anxiety and depressive symptoms after hospitalization In contrast a cluster randomized trial of a parenting intervention delivered to mothers of very premature infants from soon after birth showed no benefits for parenting stress1 The authors hypothesized that the intervention had not been of sufficient intensity particularly in the weeks surrounding discharge Neonatal care presents a significant barrier to parent-ing in the early weeks following a very preterm birth and so inter-ventions which focus on the developmental needs of infants and the parentndashchild relationship should particularly aim to support parents as they take on the parenting role There was also concern that the intervention had failed to reach those most at risk
Since large-scale projects can be costly to implement and may often fail to reach the families in most need it may be wiser to focus on intervention programmes which are more practical and easier to implement within a neonatal care setting Research has shown that even interventions which are based on one-off meet-ings with parents of sick neonates can be effective Jotzo and Poets examined the effect of an intervention programme aimed at reducing the severity of traumatic responses as a result of giv-ing birth prematurely15 Their programme consisted of a one-off intervention meeting along with additional psychological help throughout the hospitalization of the infant The meeting cov-ered a variety of issues including a reconstruction of the events shortly before and after the infantrsquos birth relaxation techniques discussion of coping strategies available resources and social support and support during emotional outbursts The measures used included the Impact of Event Scale (IES) and the Peritrau-matic Dissociative Experience Questionnaire At discharge the mothers who received the intervention were found to have a significantly lower traumatic impact as a result of premature birth Furthermore fewer mothers in the intervention group showed symptoms of clinically significant psychological trauma at discharge compared to mothers in the control group (36 vs 76)15 The lsquoParents Circle Programrsquo is another intervention with a similar structure16 This consisted of a 90 min session for parents with the aim of enhancing the developing relationship between parents and infants and to offer parents support A total of 104 parents (59 mothers and 45 fathers) and 44 members of hospital staff were asked to evaluate the programme and their results were analysed using content analysis Families reported gaining perspective on their situation feeling supported becom-ing aware of cues and optimizing interactions and becoming aware of available resources Parents and staff alike felt that participating in the intervention helped parents overcome the difficulties associated with the early time of their infantrsquos hos-pitalization Additional studies have also found positive results with fairly minimal interventions including discussion groups
7 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
in the NICU music during kangaroo care and pairing mothers of sick neonates with trained mothers who had been through similar experiences
Parent support programmes
Parent support programmes (PSPs) which are based in NICUs can provide parents with the opportunity to talk to parents who have been in similar situations and also to discuss their emo-tions with professionals who can help them cope with their situa-tion111718 The parent-to-parent support programme for mothers of preterm infants evaluated by Preyde and Ardal included edu-cational parental support group meetings and individual par-ent-to-parent support (primarily telephone support)19 Measures used included the Parental Stressor Scale NICU the State and the Trait Anxiety Inventories and the Beck Depression Inven-tory After 4 months of participation mothers in the intervention group reported lower levels of stress state anxiety and depres-sion compared to control group mothers The authors speculated however that the participants who were able to meet face to face with other parents were those who benefited the most Hurst conducted a comprehensive survey of an NICU-based PSP This PSP was provided in a variety of formats including a weekly parent support group hospital visitation and 24-h telephone sup-port20 Of the 477 participants 303 families used the PSP dur-ing a 2-year evaluation period with 78 using only one form of support and 18 using two forms Of a sub-sample of 48 parents asked to complete an evaluation of the PSP 92 stated that they would recommend such a programme to other parents Furthermore the majority of parents felt that it made them feel supported and helped them deal with their emotions20 This is an indication that such programmes can be very successful in sup-porting parents throughout their infantrsquos hospitalization It also shows that it can be beneficial to give parents several options and formats when it comes to such support services It is impor-tant to consider though that both the Hurst and the Preyde and Ardal studies found that some participants did not find the sup-port programmes helpful even reporting that they had caused them increased stress and anxiety Therefore it should not be assumed that support programmes will suit every individual and will provide the required support for all parents1920 NICUs need to be flexible enough to provide parents with a range of forms of support to choose from
The increased understanding of the strains that parents of sick neonates have to deal with has also led to efforts to improve customary practices in NICUs Family-centred care focuses on infants and their needs and attempts to redefine the relationship between parents and caregivers These practices strive to provide parents with support during their infantrsquos illness by focusing on freely sharing information and on the collaboration between parents and hospital staff Family-centred care has been found to be associated with several beneficial outcomes including improved parental satisfaction increased parental comfort staff satisfaction and decreased parental stress18 Research is already examining these practices and questioning how these can be improved further Such research reflects the increasing effort focused on lsquohumanizingrsquo the environment in NICUs in order to make parents feel more comfortable about spending time with their infants
PaeDiaTrics anD cHilD HealTH 184 19
Conclusion
Surprisingly few interventions have prioritized the provision of emotional support for parents of sick neonates or accounted for the changing needs and wishes of parents over the course of their infantrsquos care Large-scale supportive education-based inter-ventions have been shown to be effective in reducing parental distress However the feasibility and sustainability of such pro-grammes should also be considered Programmes which require significant additional resources can be expensive and there are also issues of training and quality control Interventions which require significant input from parents may also place additional burdens on families making them potentially less accessible to those most at risk Arguably the aim should be to explore ways of providing acceptable and effective informational support which could be complemented by emotional support from health professionals and from other parents in the unit Increasingly studies are exploring the use of computers and multimedia as an engaging flexible and cost-effective method of targeting indi-vidual needs and providing support and information Such com-puter-based and interactive multimedia interventions have been found to be successful with a range of patient groups and could therefore be examined as a complementary method of providing informational support to families with sick neonates
REfEREnCEs
1 Glazebrook c Marlow n israel c et al randomised trial of a
parenting intervention during neonatal intensive care Arch Dis Child
Fetal Neonatal Ed 2007 92 F438ndash443
2 singer lT salvator a Guo s collin M lilien l Baley J Maternal
psychological distress and parenting stress after the birth of a very
low-birth-weight infant JAMA 1999 281 799ndash805
3 shaw rJ Deblois T ikuta l Ginzburg K Fleisher B Koopman c
acute stress disorder among parents of infants in the neonatal
intensive care nursery Psychosomatics 2006 47 206ndash212
4 Hopper a sources of stress for parents of a sick neonate a
literature review Pediatr Nurs 2000 30 29ndash32
5 Davis l edwards H Mohay H wollin J The impact of very
premature birth on the psychological health of mothers Early Hum
Dev 2003 73 61ndash70
6 Bernazzani O saucier J-F David H Borgeat F Psychosocial
predictors of depressive symptomatology level in postpartum
women J Affect Disord 1997 46 39ndash49
7 Field T infants of depressed mothers Infant Behav Dev 1995 18
1ndash13
8 Kaplan Ps Bachorowski J-a Zarlengo-strouse P child-directed
speech produced by mothers with symptoms of depression fails
to promote associative learning in 4-month-old infants Child Dev
1999 70 560ndash570
9 ward K Perceived needs of parents of critically ill infants in
a neonatal intensive care unit (nicU) Pediatr Nurs 2001 27
281ndash286
10 lai Hl chen cJ Peng Tc et al randomized controlled trial of music
during kangaroo care on maternal state anxiety and preterm infantsrsquo
responses Int J Nurs Stud 2006 43 139ndash146
8 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
11 Tallandini Ma scalembra c Kangaroo mother care and mother-
premature infant dyadic interaction Infant Ment Health J 2006 27
251ndash275
12 Ohgi s Fukuda M akiyama T Gima H effect of an early intervention
programme on low birthweight infants with cerebral injuries
J Paediatr Child Health 2004 40 689ndash695
13 Kaaresen Pi ronning Ja Ulvund se Dahl lB a randomized
controlled trial of the effectiveness of an early-intervention program
in reducing parenting stress after preterm birth Pediatrics 2006
118 e9ndash19
14 Melnyk BM Feinstein nF alpert-Gillis l et al reducing premature
infantsrsquo length of stay and improving parentsrsquo mental health
outcomes with the creating opportunities for parent empowerment
(cOPe) neonatal intensive care unit program a randomized
controlled trial Pediatrics 2006 118 e1414ndash1427
15 Jotzo M Poets cF Helping parents cope with the trauma of
premature birth an evaluation of a trauma-preventive psychological
intervention Pediatrics 2005 115 915ndash919
16 Pearson J andersen K evaluation of a program to promote positive
parenting in the neonatal intensive care unit Neonatal Netw 2001
20 43ndash48
17 roman l lindsay J Boger r et al Parent-to-parent support
initiated in the neonatal intensive care unit Res Nurs Health 1995
18 385ndash394
18 Meyer ec coll cTG lester BM Boukydis cFZ McDonough sM Oh w
Family-based intervention improves maternal psychological well-
being and feeding interaction of preterm infants Pediatrics 1994
93 241ndash246
PaeDiaTrics anD cHilD HealTH 184 19
19 Preyde M ardal F effectiveness of a parent ldquobuddyrdquo program for
mothers of very preterm infants in a neonatal intensive care unit
CMAJ 2003 168 969ndash973
20 Hurst i One size does not fit all Parentsrsquo evaluations of a support
program in a newborn intensive care nursery J Perinat Neonatal
Nurs 2006 20 252ndash261
Practice points
bull Parents of sick neonates experience significant distress and
exhibit higher levels of stress anxiety and depression than
parents of healthy infants
bull educational support emotional support and increased
motherndashinfant contact have been shown to promote maternal
well-being
bull emotional support for fathers has been largely neglected in
the research literature
bull Parents benefit from a choice of supportive facilities which
could include face-to-face sessions with health professionals
telephone support hospital visitation parent-to-parent
support and unit-based group support meetings
bull Parentsrsquo support needs can change during their infantrsquos
hospitalization and not all parents want or benefit from the
provision of additional information and emotional support in
the neonatal unit
9 copy 2008 elsevier ltd all rights reserved
Personal Practice
When should enteral feeds be started in preterm infantsnicholas D embleton
AbstractPaediatricians are regularly faced with the question of when best to start
enteral feeds in preterm infants this is important as longer term out-
come may be compromised by sub-optimal nutrition in early life clinical
factors that may affect the decision to start and the risk and benefits
are discussed
Keywords breast milk feeding nutrition parenteral nutrition
Key points in the history
Alice is lsquonutritionally vulnerablersquo and whilst this may not be immediately apparent it will affect her long term outcome Her energy stores are extremely limited and consist primarily of pro-tein She has less than 5 fat and little energy associated with stored glycogen She is losing about 1 gkgd protein equivalent so she needs at least that and a minimum of 50ndash60 kcalkg of energy just to maintain the status quo let alone grow
Her weight is on the 25th centile Review of any antenatal his-tory may reveal whether fetal growth was normal Fetal growth retardation can occur with a weight greater than 10th centile The presence of antenatal absent or reversed end diastolic flow in the umbilical artery indicates poor gut blood flow This increases the risk of necrotizing enterocolitis (NEC) and might suggest a more cautious approach to starting feeds1
She has no important cardiovascular problems but if she were hypotensive gut blood flow may be low There is no umbilical
Nicholas D Embleton BSC (Hons) MBBS (Hons) MD FRCPCH is Consultant in
Neonatal Medicine at Newcastle Neonatal Service Royal Victoria
Infirmary Newcastle upon Tyne NE1 4LP UK
Should you start feeds at a day of age
alice was born following spontaneous labour at 30 weeksrsquo
gestation she weighed 1300 g and is now 18 h old she was
briefly ventilated and then extubated to continuous positive
airway pressure 12 h ago in 35 oxygen she has had caffeine
citrate but still has intermittent episodes of self-correcting
apnoea she was commenced on iv 10 dextrose but this was
replaced by a parenteral amino acid solution (referred to as
lsquotPnrsquo) along with intralipid at 0900 this morning serum glucose
is 11 mmoll and blood pressure is 42 systolic
PaeDiatrics anD cHilD HealtH 184 20
arterial catheter in situ but there is no good evidence that this should delay the decision to start feeds Her glucose is high but this is quite common in a baby like this Could this be a sign of sepsis Caffeine does not affect the incidence of NEC2 The great-est risk factor for NEC in this case is prematurity
What else might be found on examination
Up until 24 h ago she was swallowing large amounts of amniotic fluid What will have changed since then
General examination should confirm peripheral perfusion lsquogestaltrsquo view (does she look lsquowellrsquo) and cardiovascular status lsquoBowel soundsrsquo are not usually helpful
The most important variable likely to affect gut perfusion is the arterial duct Precordial lsquoheaversquo and a loud murmur are sug-gestive but it is possible to have a significant ductal shunt in a baby with a normal examination Cardiac ultrasound will con-firm this diagnosis It might be better to treat a large shunt first with indometacin and to delay starting feeds for a further 24 h
It is not possible to assess gut perfusion clinically but normal perfusion elsewhere (adequate urine output usually indicates adequate renal perfusion) would be reassuring Most preterm babies have a few abdominal lsquoloopsrsquo visible but a distended abdomen with many palpable loops suggests ileus This might be secondary to sepsis or poor gut blood flow Preterm babies do not pass much meconium in the first 24ndash48 h
Balance of risks between starting and withholding feeds
Alice requires 35ndash4 gkgd of protein and 120 kcalkgd to grow3 This will initially be provided parenterally Delaying feeds increases the risk of gut villous atrophy and prolongs the need for lsquototal parenteral nutrition (TPN)rsquo TPN requires intravenous access and so increases the risk of sepsis and when prolonged use is required combined with the lack of enteral feeding may result in hepatic impairment
Delaying feeds may allow a gut that has been chronically under-perfused to re-establish more normal perfusion although normal gut endocrine function digestive enzyme upregulation and motility require a source of intraluminal nutrients1 A recent study suggested benefit from delaying the introduction of feeds4 but methodologi-cal problems exist5 Although a Cochrane meta-analysis suggested no benefit only two studies were included6 A large UK-based trial is examining the effect of early or late feeding in preterm infants who were born growth retarded following identification of antena-tal absent or reversed end diastolic flow in the umbilical artery7
When starting feeds what volume should be used
There are no good data to guide this decision We start with 24 mlkg (1 mlkgh) and then increase by this amount each day Most babies achieve full enteral feeds (ge150 mlkgd) by a week of age Feeding guidelines improve the outcome8 Measure-ment or assessment of gastric aspirates is not consistently useful in predicting subsequent feeding intolerance or development of NEC Aspirate volumes equivalent to or sometimes greater than the amount given in the preceding 1ndash2 h are usually normal Most aspirates have a greenish colour Thick bloody or intensely bile-stained aspirates require detailed assessment
0 copy 2008 elsevier ltd all rights reserved
Personal Practice
What else affects decisions and outcome
Feeding success is affected by sepsis and NEC Scrupulous atten-tion should be paid to hand washing and intravenous access and blood sampling should be minimized There is no good evidence to support the routine use of pro-kinetic agents or H2 blockers
The most important clinical intervention affecting the occur-rence of NEC is the use of breast milk9 All efforts should be directed at persuading parents of the benefits and supporting the process Some clinicians delay starting feeds for a further 24 h whilst expressed breast milk becomes available Donor breast milk might be equally efficacious10
RefeRenceS
1 Dorling J Kempley s leaf a Feeding growth restricted preterm
infants with abnormal antenatal Doppler results Arch Dis Child Fetal
Neonatal Ed 2005 90 F359ndash363
2 schmidt B roberts rs Davis P et al caffeine therapy for apnea of
prematurity N Engl J Med 2006 354 2112ndash2121
PaeDiatrics anD cHilD HealtH 184 20
3 embleton nD Pang n cooke rJ Postnatal malnutrition and growth
retardation an inevitable consequence of current recommendations
in preterm infants Pediatrics 2001 107 270ndash273
4 Berseth cl Bisquera Ja Paje VU Prolonging small feeding volumes
early in life decreases the incidence of necrotizing enterocolitis in
very low birth weight infants Pediatrics 2003 111 529ndash534
5 Menon G Boyle eM embleton nD et al introduction of enteral
feeds in preterm infants Pediatrics 2004 114 327ndash328
6 Kennedy Ka tyson Je chamnanvanikij s early versus delayed
initiation of progressive enteral feedings for parenterally fed low
birth weight or preterm infants Cochrane Database Syst Rev 2000
cD001970
7 wwwnpeuoxacukadept
8 Patole sK de Klerk n impact of standardised feeding regimens on
incidence of neonatal necrotising enterocolitis a systematic review
and meta-analysis of observational studies Arch Dis Child Fetal
Neonatal Ed 2005 90 F147ndash151
9 lucas a cole tJ Breast milk and neonatal necrotising enterocolitis
Lancet 1990 336 1519ndash1523
10 Boyd ca Quigley Ma Brocklehurst P Donor breast milk versus
infant formula for preterm infants systematic review and meta-
analysis Arch Dis Child Fetal Neonatal Ed 2007 92 F169ndash175
1 copy 2008 elsevier ltd all rights reserved
self-assessment
Case 1A term male infant born to consanguineous parents is assessed at 24 h of age due to poor feeding profuse yellow watery diar-rhoea and irritability He weighed 32 kg at birth and delivery was uneventful There was no polyhydramnios He has been breastfed since birth On examination he is pale with a non-tender but distended abdomen and reduced bowel sounds His weight is 275 kg and he looks dehydrated Examination is otherwise normal
Initial investigations (normal values in parentheses) showed
sodium 149 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 65 mmollitre (25ndash75)
creatinine 147 μmollitre (40ndash110)
chloride 119 mmollitre (95ndash105)
haemoglobin 172 gdl (140ndash200)
White blood cell count 80 times 109litre (100ndash260)
Platelet count 302 times 109litre (150ndash400)
arterial blood gas
ph 720 (730ndash745)
PcO2 23 kPa (46ndash60)
Bicarbonate 68 mmollitre (220ndash260)
Base excess minus186 mmollitre (minus20 to +20)
lactate 59 mmollitre (06ndash24)
An abdominal X-ray shows distended bowel loops with no intramural thickening or pneumoperitoneum (Figure 1)
He was given nil by mouth and received intravenous fluids and antibiotics His dehydration improved but the metabolic acidosis and diarrhoea persisted despite receiving no enteral feeds and the commencement of total parenteral nutrition Blood and stool cultures were negative
1 Which of the following best describes these results Choose ONE answer ONLY from the followingA Hypernatraemia hyperchloraemic metabolic acidosis
with increased anion gapB Hypernatraemia hyperchloraemic metabolic acidosis
with normal anion gap
Manish Sadarangani BM BCh MA MRCPCH is Clinical Research Fellow
at the Department of Paediatrics University of Oxford Centre for
Clinical Vaccinology and Tropical Medicine Churchill Hospital
Oxford OX3 7LJ UK
Shabna Rajapaksa MB BChir MA MRCPCH is Specialist Registrar in
Paediatrics at the Paediatric Intensive Care Unit John Radcliffe
Hospital Oxford OX3 9DU UK
Nicholas Mann MD FRCP FRCPCH DCH is Consultant Paediatrician at the
Department of Paediatrics Royal Berkshire Hospital Reading RG1
5AN UK
self-assessment
C Hypernatraemic dehydration and compensated metabolic acidosis
D Acute renal failureE Renal tubular acidosis
2 What is the likely diagnosis Choose ONE answer ONLY from the followingA Hirschsprung disease ndash long segmentB Cystic fibrosis with meconium ileusC Microvillus inclusion diseaseD Cowrsquos milk protein intoleranceE Lactose intolerance
3 What is the investigation of choice Choose ONE answer ONLY from the followingA Rectal biopsy with staining for acetylcholine receptorsB Immunoreactive trypsinC Gastrointestinal endoscopy and biopsyD Stool microscopy and cultureE Stool reducing substances
Case 2A 4-year-old boy presents with a 3 d history of jaundice and a florid rash He has had orange urine and there is no change in his stool colour His family originate from Kosovo and have lived in the UK for the last 8 years He has never left the UK There is no history of blood transfusion or sex-ual abuse The grandmother was recently diagnosed with hepatitis B
On examination he is well apyrexial and mildly jaundiced with cervical and axillary lymphadenopathy He has an exten-sive papular rash over the face extremities and trunk (Figure 2) There is 3 cm hepatomegaly with no splenomegaly or ascites Examination is otherwise normal
Figure 1 abdominal X-ray of baby
Paediatrics and child health 184 202 copy 2008 elsevier ltd all rights reserved
self-assessment
Initial investigations are as follows
haemoglobin 110 gdl (113ndash135)
White blood cell count 108 times 109litre (50ndash150)
Platelet count 278 times 109litre (150ndash400)
inr 10 (08ndash12)
aPt ratio 10 (08ndash13)
sodium 140 mmollitre (135ndash145)
Potassium 42 mmollitre (35ndash50)
Urea 56 mmollitre (25ndash75)
creatinine 65 μmollitre (45ndash120)
total bilirubin 66 μmollitre (0ndash15)
conjugated bilirubin 23 μmollitre (0ndash10)
alanine aminotransferase (alt) 2033 iUlitre (0ndash35)
alkaline phosphatase 987 iUlitre (71ndash234)
Gamma-glutamyl transferase (GGt) 870 iUlitre (0ndash51)
1 What is the name of this rash Choose ONE answer ONLY from the followingA Erythema multiformeB Erythema migransC GianottiminusCrosti syndromeD EczemaE Dermatitis herpetiformis
2 What is the most likely diagnosis Choose ONE Answer ONLY from the followingA Autoimmune hepatitisB Hepatitis BC Hepatitis DD Wilson diseaseE Alpha-1 antitrypsin deficiency
3 What is the best means of management Choose ONE answer ONLY from the followingA Isolation until the jaundice disappearsB ImmunosuppressionC Copper chelating agents and genetic counsellingD Patient and family education with consideration of
antiviral agentsE Liver transplantation
Case 3A 10-month-old boy presents with 3 weeks of vomiting and constipation ndash he is passing hard stools every 2ndash3 days He has fallen from the 9th to below the 04th centile in the last 6 weeks He passed meconium within the first 24 h of life On examina-tion he looks pale and there are some dysmorphic features ndash a short nose long philtrum and wide mouth He has normal heart sounds with a grade 3 ejection systolic murmur loudest at the upper right sternal edge Examination is otherwise normal
Initial investigations are as follows
haemoglobin 91 gdl (113ndash141)
total white blood cell count 124 times 109litre (60ndash170)
Platelet count 407 times 109litre (150ndash400)
sodium 144 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 78 mmollitre (25ndash75)
creatinine 78 μmollitre (45ndash120)
albumin 52 glitre (35ndash50)
corrected calcium 384 mmollitre (238ndash263)
Phosphate 167 mmollitre (099ndash157)
1 What is the most likely diagnosis Choose ONE answer ONLY from the followingA HyperparathyroidismB Acute leukaemiaC Williams syndromeD Hypervitaminosis DE Familial hypocalciuric hypercalcaemia
2 Which investigation would be most useful in establishing the diagnosis Choose ONE answer ONLY from the followingA Intact parathyroid hormone assayB Blood filmC Fluorescent in-situ hybridization for 7q1123 deletionD 25-hydroxyvitamin D assayE Urine calciumcreatinine ratio
3 Which of the following treatments would not be suitable for this patient Choose ONE answer ONLY from the followingA Low calcium dietB Normal saline infusionC FurosemideD CorticosteroidsE Bisphosphonates
Case 4A 10-week-old girl presents with a 2-day history of poor feed-ing Her mother has been concerned about weakness since birth She only has a flicker of movement in the arms none in the legs and has a weak cry She has been passing urine and opening her bowels normally She was born at full term by normal delivery and did not require any resuscitation at birth Normal fetal movements were felt antenatally and there was no polyhydramnios She is the first child of non- consanguineous parents and there is no significant family his-tory On examination she is alert and fixing and following appropriately She has a weak cry and a weak suck There is reduced central and peripheral tone with marked head lag
Figure 2 rash found on examination
Paediatrics and child health 184 203 copy 2008 elsevier ltd all rights reserved
self-assessment
Muscle power is grade 3 out of 5 in the arms and legs There is no muscle or tongue fasciculation and she has absent reflexes throughout The remainder of the examination is normal
Electromyogram shows irregular polyphasic motor unit potentials with marked instability consistent with a dener-vating and re-innervating process (Figure 3)
1 Which of the following additional investigations may be helpful Choose ONE answer ONLY from the followingA Nerve conduction studiesB Creatine kinase assayC Muscle biopsyD SMN1 gene analysisE All of the above
2 What is the most likely cause of this childrsquos symptoms Choose ONE answer ONLY from the followingA Congenital myotonic dystrophyB Duchenne muscular dystrophyC PraderminusWilli syndromeD Spinal muscular atrophyE Mitochondrial myopathy
3 What is the mode of inheritance of this disease Choose ONE answer ONLY from the followingA X-linked recessiveB Autosomal recessiveC Autosomal dominantD MitochondrialE Sporadic
Case 5A 13-year-old girl presents with a 3-week history of fever up to 40degC night sweats and headache She has a reduced appetite with some weight loss She has no other specific symptoms She was on holiday in China 7 months ago On examination she looks well and has a temperature of 387degC There is no lymphadenopathy and no rashes Examination is entirely normal
Results of investigations are as follows
haemoglobin 126 gdl (120ndash160)
total white blood cell count 132 times 109litre (43ndash108)
neutrophil count 115 times 109litre (25ndash75)
Platelet count 244 times 109litre (150ndash400)
Blood film neutrophilia with left shift
erythrocyte sedimentation rate 63 mmh (1ndash20)
c-reactive protein 219 mglitre (0ndash5)
Blood culture Streptococcus intermedius
from anaerobic bottle only
csf culture negative
Magnetic resonance imaging (MRI) of the brain shows acute frontal sinusitis with a large intracranial frontal extra-dural empyema (Figure 4)
1 Which of the following would be appropriate management Choose ONE answer ONLY from the followingA A 12-week course of intravenous antibioticsB Drainage of the frontal sinus followed by 2 weeks of
intravenous antibioticsC Drainage of the empyema followed by 2 weeks of
intravenous antibioticsD Drainage of the empyema and the frontal sinus
followed by 2 weeks of oral antibiotics
1151
1152
1153
1154
1155
1156
1157
1158
1159
1200
50ms 1mV
Figure 3 electromyogram recording from the patient Figure 4 Parasagittal section from mri scan of patient
Paediatrics and child health 184 204 copy 2008 elsevier ltd all rights reserved
self-assessment
E Drainage of the empyema and the frontal sinus followed by 8 weeks of intravenous antibiotics
2 Streptococcus intermedius is a potential pathogen in which of the following infections Choose ONE answer ONLY from the followingA Liver abscessB Urinary tract infectionC MeningitisD Thoracic empyemaE Pneumonia
3 Which of the following statements regarding lsquopyrexia of unknown originrsquo in children is false Choose ONE answer ONLY from the followingA Malignancy is the underlying pathology in 5ndash15 of
casesB An aetiology will be found in over 90 of casesC The most common cause is infectionD A rheumatological cause is found in 10ndash20 of casesE Familial Mediterranean fever can occur in children of
non-Mediterranean ethnicity
Answers
Case 11 AThe anion gap is a useful tool to differentiate the causes of a metabolic acidosis It is calculated by the equation
Anion gap = [Na K ] [Cl HCO ]3+ + minus minus+ minus +
It represents the effect of unmeasured anions on the plasma pH and is normally 10ndash18 mmollitre
2 CMicrovillus inclusion disease is a severe autosomal recessive enteropathy that is typically apparent within hours or days after birth It is the second most common cause of protracted diarrhoea in the newborn after infectious causes It is characterized by severe yellow watery diarrhoea and malabsorption due to hypoplasia andor atrophy of the villi of the small intestine secondary to an inherited defect in the brush border membrane This results in severe dehydration malnutrition and metabolic acidosis due to bicarbonate loss from the gut
3 CDiagnosis of microvillus inclusion disease is made on small bowel biopsy Electron microscopy findings are of intracellular brush border inclusions and densely packed apical cytoplasmic vesicular bodies indicating microvillous atrophy There is no cure Treatment is supportive with total parenteral nutrition and consideration of small bowel transplantation
Further reAding
Goulet O ruemmele f causes and management of intestinal failure
in children Gastroenterology 2006 130(suppl 1) s16ndash28
rhoads Jm Vogler rc lacey sr et al microvillus inclusion disease
In vitro jejunal electrolyte transport Gastroenterology 1991
100 811ndash817
Case 21 CGianottindashCrosti syndrome is a distinct self-limiting rash commonly associated with viral infections in children between 2 and 6 years of age It presents as multiple pink to redminusbrown papules or papulovesicles which may be pruritic and can become confluent Gianotti and Crosti initially described the exanthema as associated with hepatitis B virus and they termed it papular acrodermatitis of childhood It can occur in several viral diseases eg hepatitis A B and C coxsackie viruses and cytomegalovirus
2 BHepatitis is a syndrome characterized by inflammation or injury of liver cells which may develop into cell necrosis and subsequently fibrosis andor cirrhosis Biochemically there are raised liver enzymes The degree of transaminase elevation does not correlate with the severity of the disease process Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of viral hepatitis
3 DHepatitis B infection is transmitted via blood sexually or vertically Infection may be acute or chronic Diagnostic markers are the presence of surface antigen (HBsAg) and HBV DNA The presence of e antigen (HBeAg) indicates high infectivity Infected newborns have a 95 risk of becoming carriers this risk decreases with infection acquired later in childhood Approximately 15ndash25 of HBV carriers will die from cirrhosis or hepatocellular carcinoma Extrahepatic findings are more common in older children and include membranous glomerulonephritis and GianottiminusCrosti syndrome Fulminant hepatic failure occurs in severe cases resulting in persistent jaundice encephalopathy and coagulopathy Management includes counselling family members monitoring for ongoing liver disease and consideration of antiviral therapy
Further reAding
Brandt O abeck d Gianotti r Burgdorf W Gianotti crosti
syndrome J Am Acad Dermatol 2006 54 136ndash145
slowik mK Jhaveri r hepatitis B and c viruses in infants and
young children Semin Pediatr Infect Dis 2005 16 296ndash305
Case 31 CHypercalcaemia is uncommon in infancy The most common symptoms in this age group are irritability vomiting and constipation It may be a manifestation of Williams syndrome vitamin D or calcium excess as well as disorders associated with reduced bone formation such as hypophosphatasia or increased bone resorption such as malignancy Occasionally
Paediatrics and child health 184 205 copy 2008 elsevier ltd all rights reserved
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-
SympoSium neonatology
at this crucial time411 Clearly during this catabolic phase of immediate postnatal nutrition prior to the establishment of suck-ling feeds provision of energy for vital organ function is at the expense of growth and fuel storage
The postnatal metabolic transition is characterized by low cir-culating blood glucose concentrations compared to those of older infants and children often for a number of days12 This is almost always of no pathological significance for a number of reasons including differences in the function and metabolic requirements of the brain and importantly the production and utilization of alter-native fuels lactate and ketone bodies which are in plentiful supply in the neonate341213ndash20 An important finding from clinical studies and of clinical relevance to those caring for mothers and babies is that in all groups of infants studied to date those who are breast fed have higher circulating ketone body levels than those who are formula fed even after correcting for blood glucose levels102122
There are circumstances however when hypoglycaemia is severe and prolonged and conditions when alternative fuel pro-duction is also impaired or fails In these circumstances low blood glucose levels do acquire clinical significance The key metabolic processes and the risk factors for impaired metabolic adaptation are summarized in Table 1
Metabolic changes at birth ndash key hormones and metabolic processes and risk factors for impaired metabolic adaptation
Postnatal metabolic
changes
Risk factors
Hormones
insulin falls neonatal hyperinsulinism ndash infant of
diabetic mother or idiopathic
glucagon surge possibly blunted by iv glucose or
formula feeds
Catecholamine surge maternal beta-blocker medication
(Cortisol ndash weak effect) (pituitary or adrenal insufficiency)
Metabolic processes
glygogenolysis preterm intrauterine growth
restriction (iugR) ndash reduced stores
perinatal hypoxia-ischaemia ndash stores
utilized
Hyperinsulinism
maternal beta-blocker medication
glycogen storage disorders
gluconeogenesis Hyperinsulinism
maternal beta-blocker medication
Hepatic dysfunction
Very rare inborn errors of metabolism
lipolysis preterm iugR ndash reduced stores
Hyperinsulinism
maternal beta-blocker medication
Ketogenesis Defects of beta-oxidation of fatty
acids
Hepatic dysfunction
Table 1
paeDiatRiCS anD CHilD HealtH 184 16
Impaired metabolic adaptation
Risk factors for impaired metabolic adaptation vary and may be related to any of the following reduced body fuel stores failure of the normal endocrine changes at birth systemic illnesses which impede function of the liver where the key metabolic processes occur or rarely inborn errors of metabolism (see Table 1)
It is well recognized that significant hypoglycaemia will result in a reduced level of consciousness andor fits However it is always important to be alert for detect and treat an underlying pathology which could be causing both the hypoglycaemia and the abnormal signs Often abnormal signs and hypoglycaemia are co-morbidities eg a primary neurological problem causes both abnormal neurological signs and hypoglycaemia secondary to poor feeding For this reason all possible underlying causes for presentation with hypoglycaemia must be considered and investigations planned accordingly Investigations for inborn errors of metabolism and endocrine disorders are most informa-tive if carried out when blood glucose levels are low
There have been extensive efforts to use data from clinical stud-ies of the human neonate to determine the significance of neonatal hypoglycaemia in terms of neurophysiological neurodevelopmental and neuroradiological sequelae However there are major difficul-ties in interpreting these clinical studies as to date these have been flawed by confounding factors such as immaturity placental insuf-ficiency and co-existing complications by heterogeneity of subjects and by failure to take into account protective mechanisms11423 The evidence from both animal and human studies suggests lsquopurersquo hypo-glycaemic brain injury is rare and for hypoglycaemic brain injury to occur there must be co-existing failure of metabolic adaptation such that alternative fuels are not available There is no evidence that lsquotransitionalrsquo hypoglycaemia in the healthy neonate is associated with acute or long term sequelae and indeed even for babies in the at-risk groups on many occasions protective factors will prevail
Diagnosis of clinically significant hypoglycaemia
lsquoNeonatal hypoglycaemiarsquo is a commonly cited diagnosis most often based on a single blood glucose level and using inaccurate methods of measurement and with disregard for the presence or absence of associated clinical signs In the many published texts and local guidelines there is no consistency of approach For this reason a multinational group of experts attempted to examine critically the evidence on which clinical recommendations should be made1 Fol-lowing detailed analysis the authors considered it impossible to define hypoglycaemia as a single blood glucose level and instead suggested operational thresholds and therapeutic goals They con-cluded that low blood glucose levels accompanied by neurological signs should be investigated and treated regardless of the blood glu-cose level They also pragmatically concluded that a blood glucose level below 10 mmollitre should be treated immediately In babies who are at risk of impaired metabolic adaptation but who have no clinical signs it is recommended that interventions to raise blood glucose level are considered if blood glucose levels are persistently below 20 mmollitre For sick and very low birthweight babies who are likely to have a requirement for intravenous glucose there should be a lsquotherapeutic goalrsquo to maintain blood glucose levels above 25 mmollitre Where there is known hyperinsulinism (a very high-risk condition characterized by high intravenous glucose
2 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
requirements to maintain normoglycaemia) an operational thresh-old and therapeutic goal of 35 mmollitre has been proposed24
Finally there must be careful consideration of the infant of the diabetic mother In extreme and rare cases there may be signifi-cant but transient hyperinsulinism and in these cases the thera-peutic goal must be 35 mmollitre More commonly babies whose mothersrsquo diabetes has been well controlled will have normal lsquotran-sitional hypoglycaemiarsquo or slightly delayed metabolic adaptation while insulin levels fall postnatally There must be careful and repeated clinical assessment including blood glucose monitoring For infants of diabetic mothers who have no evidence of signifi-cant hyperinsulinism and no abnormal clinical signs there is no evidence that the operational threshold for hyperinsulinism must be applied Indeed to do so would result in separation of large numbers of healthy babies from their mothers with the conse-quent impact upon breast feeding and resource allocation25
The operational thresholds for various groups of babies are summarized in Table 2
The guidance relating to operational thresholds is predicated upon the accurate measurement of blood glucose levels It is now well known that the commonly used reagent strips are insufficiently accurate to diagnose hypoglycaemia and monitor at-risk infants and there must be access to equipment which allows immediate and accurate determination of blood glucose levels1426ndash28
Blood glucose monitoring
An accurate method for blood glucose monitoring must be employed as described above The sample should be free flowing venous or from a warm heel such that the blood flows freely without squeezing
Blood of high haematocrit often yields low blood glucose lev-els because of dilution of glucose by red cell water However this is also clinically relevant because polycythaemia is itself a high-risk situation Therefore in polycythaemic infants both the haematocrit and blood glucose level must be monitored and both acted upon accordingly
Operational thresholds for blood glucose levels in the management of babies at risk of impaired metabolic adaptation124
Clinical condition Blood glucose level at which
to consider intervention and
therapeutic goal
all at-risk babies lt10 mmollitre
abnormal neurological
signs
intervene regardless of blood
glucose levelSystematically unwell baby therapeutic goal of 25 mmollitre
at-risk babies no abnormal
neurological signs
persistently lt20 mmollitre
Hyperinsulinism 35 mmollitre
Table 2
paeDiatRiCS anD CHilD HealtH 184 163
Only babies in at-risk groups or babies who have abnormal neurological signs should be subjected to blood glucose monitor-ing (Table 3)
It is important not to commence blood glucose monitoring too soon after birth as to do so would fail to differentiate the baby with incipient hypoglycaemia from the baby undergoing the nor-mal postnatal fall in blood glucose level It is recommended in the otherwise healthy but at-risk baby to wait until around 3 h after birth to make the first blood glucose estimation2528 In prac-tice this is usually before the second feed assuming best practice of offering a baby a breast (or if necessary formula feed) imme-diately after birth Clearly if the baby is unwell or has abnormal clinical signs in the first 3 h they will be treated according to clinical condition which will include intravenous fluids and the therapeutic goal described above would apply
Similarly the temptation to measure blood glucose level shortly (within 2 h) after intravenous glucose has been discon-tinued must be avoided In this circumstance as at birth blood glucose levels fall and then subsequently rise in response to coun-ter-regulation It is this effective rise which must be assessed by blood glucose measurement at least 2 h after a change is made (provided the baby remains clinically well)
Blood glucose levels rise after a feed and fall to a nadir before the subsequent feed As our concern is the lowest blood glucose level during the feed cycle and as this measurement may assist in determining best feed frequency it is important that pre-feed blood glucose concentration is measured There is no clinical value in measuring a post-feed blood glucose level as this may be falsely reassuring and this practice subjects babies to more frequent heel pricks or venesections than is necessary
Finally consideration must be given to when to discontinue blood glucose monitoring This will depend upon the babyrsquos clin-ical condition feeding pattern and underlying disorder or risk factors for impaired metabolic adaptation
Prevention and management of clinically significant hypoglycaemia
In babies at risk of clinically significant hypoglycaemia and who are well enough to tolerate enteral feeds milk feeds are the
At-risk babies for whom blood glucose monitoring is recommended
abnormal neurological signs
Systemically unwell eg suspected or proven infection
hypoxicndashischaemic encephalopathy
preterm (lt 37 weeks)
intrauterine growth restriction (lt 2nd centile and any baby with
signs of wasting)
infant of diabetic mother
polycythaemia
maternal beta-blocker medication
Suspected hyperinsulinism
Suspected inborn error of metabolism or endocrine disorder
Table 3
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
mainstay of prevention For babies who are able to feed orally breast feeding should be first choice and there must be maximal support for the mother to do so This is a key clinical priority for midwives and paediatricians
If there are concerns regarding adequacy of breast feeding to prevent hypoglycaemia the mother should be encouraged to commence expression of milk from very soon after birth If there is insufficient breast milk to prevent babies reaching the opera-tional thresholds described above there should be judicious use of formula milk using only the smallest amount required to keep the babyrsquos glucose in the required range Formula milk in exces-sive quantities has been demonstrated to suppress normal meta-bolic adaptation2122
In babies for whom early enteral feeds are not appropriate or not tolerated or for whom enteral feeding does not prevent blood glucose level falling below operational thresholds intravenous glucose infusion at rates around 4ndash5 mgkgmin (58ndash72 mlkgd of 10 dextrose) are usually sufficient to prevent hypoglycae-mia If blood glucose levels remain below therapeutic goals the rate of infusion may be steadily increased Excess glucose infu-sion over and above that required to maintain the therapeutic goal will stimulate insulin and there is a risk of rebound hypo-glycaemia if high rate glucose infusions are too rapidly reduced Milk feeds if tolerated should be continued if intravenous glu-cose is commenced
If infused volume of glucose solution becomes excessive in order to maintain therapeutic goals or if fluid restriction must be applied more concentrated glucose concentrations must be infused through a central venous line This is particularly rel-evant to the hyperinsulinaemic baby in whom glucose infusion rates in excess of 8ndash10 mgkgmin are required to maintain ther-apeutic goals There is a high risk of severe and brain-damaging hypoglycaemia if treatment is delayed or fails to raise blood glu-cose levels and management of these babies requires consulta-tion with or referral to a specialist centre24
If there is presentation of hypoglycaemia with abnormal clinical signs or a very low blood glucose level (less than 1 mmollitre) this mandates urgent treatment with intravenous glucose The rates of glucose infusion described above are usually sufficient to bring the blood glucose level rapidly to the therapeutic goal without a bolus of glucose being necessary In fact a bolus dose of glucose will result in a peak blood glucose level and then an insulin surge making subsequent management problematical This is minimized by the use of a lsquomini-bolusrsquo should a bolus of glucose be required ndash 200 mg glucosekg (2 mlkg of 10 dextrose)28 Indications for mini-bolus are infants presenting with fits or coma or an lsquounre-cordablersquo or zero blood glucose level A mini-bolus should always be followed with glucose infusion or an increased glucose infusion rate if a baby already receiving intravenous glucose has required a mini-bolus
The temptation to supplement enteral feeds with glucose polymers and energy supplements (eg Duocal) or to use oral glucose gels or solutions (eg Hypostop) should be avoided as this carries a risk of necrotizing enterocolitis is likely to suppress normal metabolic adaptation and will suppress the appetite of the baby for effective oral feeding
Finally there are additional medications which may be employed in specific circumstances (Table 4) More detailed descriptions are given elsewhere242728 Babies who have hypoglycaemia which
paeDiatRiCS anD CHilD HealtH 184 164
is difficult to control by the measures described above and who require these additional treatments should be cared for in a centre which has expertise in metabolic and endocrinological conditions
Summary
Much controversy and confusion has surrounded neonatal hypo-glycaemia but this usually arises as a result of failure to under-stand the processes of normal metabolic adaptation and the fact that hypoglycaemia is a presenting sign rather than a diagnosis in itself Plans for investigation and management must be based upon the most likely underlying cause of impaired metabolic adaptation and take into account the clinical condition of the baby This is counter to the current trend to propose rigid pro-tocols and algorithms and re-introduces the value of detailed clinical evaluation and decision making The mainstay of man-agement is close clinical observation of vulnerable infants and energy provision tailored to their individual needs whilst avoid-ing excessively invasive management (namely unnecessary sep-aration of mother and baby routine or excessive formula milk supplementation or intravenous glucose administration) which themselves inhibit protective metabolic responses and impede successful establishment of breast feeding
ReFeRenCeS
1 Cornblath m Hawdon Jm Williams aF et al Controversies regarding
definition of neonatal hypoglycemia Suggested operational
thresholds Pediatrics 2000 105 1141ndash1145
2 Cornblath m ichord R Hypoglycemia in the neonate Semin
Perinatol 2000 24 136ndash149
3 Vannucci RC Vannucci SJ Hypoglycaemic brain injury Semin
Neonatol 2001 6 147ndash155
4 Rozance pJ Hay WW Hypoglycaemia in newborn infants features
associated with adverse outcomes Biol Neonate 2006 90 74ndash86
5 Hawdon Jm Hypoglycaemia in newborn infants defining the
features associated with adverse outcomes ndash a challenging remit
Biol Neonate 2006 90 87ndash88
6 Williams aF neonatal hypoglycaemia clinical and legal aspects
Semin Fetal Neonatal Med 2005 10 363ndash368
7 Soothill pW nicolaides KH Campbell S prenatal asphyxia
hyperlacticaemia hypoglycaemia and erythroblastosis in growth
retarded fetuses BMJ 1987 294 1051ndash1053
Additional medication in specific conditions (if these are required there must also be referral to a specialist centre)
Medication Indication
glucagon intramuscular bolus dose of 200 μgkg
transient rise in blood glucose level eg
when difficulty re-siting intravenous infusion
Diazoxide Hyperinsulinism
Hydorcortisone pituitary or adrenal insufficiency
Table 4
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
8 Hawdon Jm Ward platt mp mcphail S Cameron H Walkinshaw Sa
prediction of impaired metabolic adaptation by antenatal Doppler
studies in small for gestational age fetuses Arch Dis Child 1992
67 787ndash792
9 Deshpande S Hawdon Jm et al adaptation to extrauterine life in
Rodeck C Whittle m eds Fetal medicine Basic Science and Clinical
practice edinburgh Churchill livingstone 1999
10 Ward platt m Deshpande S metabolic adaptation at birth Semin
Fetal Neonatal Med 2005 10 341ndash350
11 eyre Ja Stuart ag Forsyth RJ Heaviside D Bartlett K glucose
export from the brain in man evidence for a role for astrocytic
glycogen as a reservoir of glucose for neural metabolism Brain Res
1994 28 349ndash352
12 Hawdon Jm Ward platt mp aynsley-green a patterns of metabolic
adaptation for preterm and term infants in the first neonatal week
Arch Dis Child 1992 67 357ndash365
13 Hawdon Jm Ward platt mp aynsley-green a prevention and
management of neonatal hypoglycaemia Arch Dis Child Fetal
Neonatal Ed 1994 70 F60ndash64
14 Hawdon Jm Hypoglycaemia and the neonatal brain Eur J Paediatr
1999 158 S9ndash12
15 massieu l Haces ml montiel t Hernaacutendez-Fonseca K acetoacetate
protects hippocampal neurons against glutamate-mediated neuronal
damage during glycolysis inhibition Neuroscience 2003 120
365ndash378
16 yamada Ka Rensing n thio ll Ketogenic diet reduces
hypoglycaemia-induced neuronal death in young rats Neurosci Lett
2005 385 210ndash214
17 nehlig a Brain uptake and metabolism of ketone bodies in animal
models Prostaglandins Leukot Essent Fatty Acids 2004 70
265ndash275
18 Hernaacutendez mJ Vannucci RC Salcedo a Brennan RW Cerebral blood
flow and metabolism during hypoglycemia in newborn dogs
J Neurochem 1980 35 622ndash628
19 Vannucci RC nardis ee Vannucci SJ Campbell pa Cerebral
carbohydrate and energy metabolism during hypoglycaemia in
newborn dogs Am J Physiol 1981 256 H1659ndashH1666
20 anwar m Vannucci RC autoradiographic determination of regional
cerebral blood flow during hypoglycaemia in newborn dogs Pediatr
Res 1988 24 41ndash45
21 Hawdon Jm Williams aF et al Formula supplements given to
healthy breastfed preterm babies inhibit postnatal metabolic
adaptation results of a randomised controlled trial Arch Dis Child
2000 82 a30
paeDiatRiCS anD CHilD HealtH 184 16
22 de Rooy l Hawdon Jm nutritional factors that affect the postnatal
metabolic adaptation of full-term small- and large-for gestational
age infants Pediatrics 2002 109 e42
23 Hawdon Jm Hypoglycaemia and brain injury ndash when neonatal
metabolic adaptation fails in levene m ed Fetal and neonatal
neurology and neurosurgery edinburgh Churchill livingstone in
press
24 Hussain K Congenital hyperinsulinism Semin Fetal Neonatal Med
2005 10 369ndash376
25 acolet D Diabetes in pregnancy Caring for the Baby after Birth
CemaCH 2007 2
26 Hussain K Sharief n the inaccuracy of venous and capillary blood
glucose measurement using reagent strips in the newborn period
and the effect of haematocrit Early Hum Dev 2000 57 111ndash121
27 Hawdon Jm Disorders of blood glucose homeostasis in the neonate
in Rennie Jm ed Robertonrsquos textbook of neonatology 4th edn
edinburgh Churchill livingstone 2005
28 Deshpande S Ward platt mp the investigation and management
of neonatal hypoglycaemia Semin Fetal Neonatal Med 2005 10
351ndash361
Practice points
bull identify risk factors for impaired metabolic adaptation
bull Clinical monitoring including accurate blood glucose
measurement for at-risk babies
bull Feed at-risk babies soon after birth and maintain thermal
homeostasis
bull take first blood glucose level at 3ndash4 h of age
bull intervene in at-risk baby with no clinical signs if two
consecutive blood glucose measurements lt 20 mmollitre
bull intervene in any baby with blood glucose measurement
lt 10 mmollitre
bull intervene in any baby with abnormal clinical signs regardless
of blood glucose level
bull investigate for underlying cause of failure of metabolic
adaptation
bull maintain lactation and breast feeding
5 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Resuscitation of the term and premature babyJonathan Wyllie
Abstractalthough most newly born babies establish normal respiration and
circulation without help up to 1minus2 may require some resuscitation
or stabilization Babies who do not establish adequate regular normal
breathing or who have a heart rate of less than 100 beatsmin or other
problems such as prematurity may require assistance the differences in
approach to the resuscitation of such babies originate in the physiology
and pathophysiology of acute asphyxia at birth However management
of airway and breathing remain the key features of resuscitation and
where cardiac depression has occurred this is nearly always due to hy-
poxia secondary to respiratory compromise therefore most babies will
respond within 2minus3 min of effective aeration of the lungs and the need
for intubation chest compressions or drugs is rare the international
liaison Committee on Resuscitation (ilCoR) evaluated evidence in 2000
and 2005 in order to provide guidelines for resuscitation they will do
so again for 2010 this evidence is limited in terms of both quantity and
quality and controversies still exist more research is needed to ensure
that our future actions are based upon evidence rather than history this
article will review the recommended approach to resuscitation as well as
some newer evidence
Keywords guidelines neonatal newborn premature resuscitation
Background
In the UK 669 601 babies were born alive in 2006 and most made the transition to extrauterine life without problems Those babies who did not establish adequate regular normal breathing or who had a heart rate of less than 100 beatsmin may have required assistance1 Factual evidence concerning the true requirement for resuscitation at birth is sparse Up to 10 of newborns may require some assistance to begin breathing with less than 1 needing extensive resuscitation2 However just because a baby received resuscitation does not necessarily mean that it was required and rates of intervention may be altered by educa-tion34 or the personnel present at deliveries5 In a UK tertiary centre with a standard approach to resuscitation at birth up to 12 of all babies received some airway assistance with just over 1 being intubated3 In Sweden only 1 of babies over 2500 g required mask or endotracheal tube ventilation at birth of which most responded to the former4
Jonathan Wyllie MBChB FRCPCH is Consultant Neonatologist at the James
Cook University Hospital Marton Road Middlesbrough TS4 3BW UK
paeDiatRiCS anD CHilD HealtH 184 16
Sometimes it is possible to predict babies who are likely to have respiratory depression at birth and to have appropriate per-sonnel present at delivery Guidelines for attendance at deliveries will vary with institution but even when almost 40 of deliv-eries are attended there may still be a further 15 of babies who require unexpected resuscitation5 a proportion that seems to remain whatever changes are made
The physiology of babies requiring help at birth has been summarized previously167 It allows a logical approach to resus-citation (Figure 1) when evidence is lacking and may prompt further research
Resuscitation at birth
PreparationAt birth resuscitation is more likely in babies with intrapartum evidence of significant fetal compromise those less than 35 weeksrsquo gestation those delivering vaginally by the breech and in multiple births Personnel trained in newborn resuscitation should be available at every delivery1 Someone experienced in tracheal intubation and advanced resuscitation should also be easily available for normal low-risk deliveries in hospital and ideally in attendance for deliveries with an increased likelihood of needing resuscitation In the latter cases the equipment and environment can be prepared beforehand including a discussion with the parents Wash your hands put on gloves and consider what help may be needed
Cord clampingAt birth it has long been known that delay in clamping the cord will lead to less anaemia in babies and reduce subsequent iron deficiency8 However few hospitals have practised this interven-tion due to worries about hypothermia and the need to resusci-tate or stabilize babies In developed countries the advantages seemed to be outweighed by the potential disadvantages A recent randomized controlled study of delayed clamping of the cord in premature babies found that the intervention group had less late-onset sepsis and fewer intraventricular haemorrhages9 This is a low-risk strategy which needs further evaluation in order to introduce it without increasing other risk factors in pre-mature deliveries
Assessment and temperature controlAssessment and temperature control for the newborn baby should occur at all deliveries The assessment indicates the need for resuscitation Babies may vary from 23 to 40+ weeksrsquo ges-tation and in weight from 500 to 5000 g They are born naked and wet and if left cannot cope with an environmental tem-perature of less than 32degC However if the term baby is imme-diately dried put skin-to-skin with the mother and covered the delivery room temperature can be as low as 25ndash28degC Obviously the smaller the baby the greater the surface area to mass ratio and the greater the risk of hypothermia Compromised babies are particularly vulnerable10 and hypothermia will lower oxygen tension11 increase metabolic acidosis12 and inhibit surfactant production13
An effective method of maintaining the temperature of prema-ture babies less than 28 weeksrsquo gestation is wrapping them with plastic before drying and then placing them under a radiant
6 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Dry the babyRemove any wet towels and cover
Start the clock or note the time
Give 5 inflation breathsLook for a response
If no increase in heart rate look for chest movement
Re-check head positionApply Jaw thrust
Repeat inflation breathsLook for a response
If no increase in heart rate look for chest movement
Try alternative airway opening manoeuvresRepeat inflation breaths
Look for a response
If no increase in heart rate look for chest movement
If the heart rate is not detectable or slow (lt60)Start compressions
3 compressions to each breath
Reassess heart rate every 30 secondsConsider venous access and drugs
Assess colour tone breathing and heart rate
Open the airway
If not breathing
If still not breathing
If no response
If still no response
When the chest is moving
If meconium present
Baby breathing wellDo not suction the airway
Baby floppy and not breathing wellConsider inspection and suction before
inflation breaths
Head in neutral position
Inflation breathsUse a well-fitting face mask
connedted to a
pressure-limited gas supply
Each breath 2ndash3 seconds
duration at 30 cm H2O for a
term baby
Get help from a second personto support the airway andor
inspect the oropharynx under
direct vision and consider
suction andor insert an
oropharyngeal airway
Chest compressionsCompvent ratio 31
Rate 120 events per minute
Ensure the chest moves with each ventilation breath
If breathingReassess heart rate and monitor baby
If heart rate is satisfactory but increasingContinue ventilation breaths at about 30 per
minute until baby is breathing adequately
If heart rate is satisfactory but increasingContinue ventilation breaths at about 30 per
minute until baby is breathing adequately
If heart rate is increasingStop compressions
Continue ventilation breaths at about 30 per
minute until baby is breathing adequately
If the chest is not movingRecheck head position and repeat inflation
breaths If competent consider intubation
If the chest is still not movingThe airway is the problem
Figure 1 newborn life support (Courtesy of the Resuscitation Council uK)
heater14 There is a small risk of hyperthermia so the temperature must be monitored carefully
An assessment is made of the babyrsquos colour tone respira-tions and heart rate127 The most important of these is heart rate and a stethoscope is more reliable than cord pulsation15 How-ever saturation monitors may offer a more reliable assessment of both heart rate and colour16 but their interpretation requires a detailed knowledge of normal saturations at birth at differing gestations A baby who is apnoeic and floppy in the absence of neurological disease is unconscious and likely to be in terminal apnoea however this does not change the initial approach other
paeDiatRiCS anD CHilD HealtH 184 167
than the need to summon help early APGAR scores are never calculated to guide resuscitation
Airway
If a baby is in primary apnoea then with an open airway the first gasp will start to aerate the lungs and most babies will be able to lsquoresuscitatersquo themselves as shown in physiological stud-ies on animals Neutral positioning of the babyrsquos head chin lift jaw thrust oropharyngeal airways and endotracheal intubation may all be helpful in certain situations if performed correctly17
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Endotracheal intubationThe placement of an endotracheal tube has long been the gold standard of airway control and this remains true in the unconscious baby if it is correctly sized placed and fixed in a timely manner However experience is directly related to effec-tiveness in endotracheal intubation1819 and the success rate of less experienced clinicians such as a resident (STA1-3) or a fel-low (STA3-5) is lower varying between 33 and 68 Even senior neonatologists often take longer than guidelines recom-mend19 Experienced clinicians may judge correct endotracheal position visually or by an increase in heart rate with the first breaths but detection of exhaled carbon dioxide will give more rapid confirmation in larger babies12171920 and this can be par-ticularly useful for less experienced clinicians or those supervis-ing them However not all systems for the detection of exhaled carbon dioxide work in the smallest premature infants
Laryngeal masksLaryngeal masks may be effective for ventilating term newborn babies but there are few data for small premature infants There have been reports of dislodged laryngeal airways during paedi-atric arrests when chest compressions have been administered Although success of placement at first attempt by paediatri-cians is greater with a laryngeal mask than with an endotra-cheal tube21 the only and small randomized controlled trial in the delivery room favoured endotracheal intubation when per-formed by an anaesthetist22 Based mainly upon case reports the laryngeal mask can be recommended when positioning and mask ventilation and endotracheal intubation have failed to secure the airway but not as yet as a primary method of airway control
MeconiumIn 2000 Wisewell et al23 reported a large randomized controlled trial showing that tracheal intubation and suctioning of meco-nium-stained but vigorous babies at birth did not reduce the incidence or severity of meconium aspiration syndrome More recently another randomized trial has now shown that suction-ing on the perineum similarly offers no benefit24 Neither of these practices is recommended but intubation and suction of meconium from the trachea of non-vigorous babies born through meconium-stained liquor is still recommended
Breathing
In the apnoeic baby the first breaths establish the resting lung volume and aerate the fluid-filled alveoli This mechanical effect aided by surface tension within the alveoli causes the initial fall in pulmonary vascular resistance Experimentally this effect occurs even if the lungs are ventilated with nitrogen but is increased when air is used presumably due to the vasodilator effect of 21 oxygen The mechanical stretching of the lung also triggers the activation of cyclo-oxygenase beginning the production of prostacyclin Bradykinin is produced which has a further direct vasodilator effect and also possibly via prostacyclin Therefore adequate airway control and passive ventilation is vital not only because babies requiring resuscitation at birth have an almost uniformly respiratory aetiology but also in order to promote post-natal adaptation and reverse any maladaptation
paeDiatRiCS anD CHilD HealtH 184 16
In term babies peak ventilatory pressures of 20ndash30 cmH2O may be required but the minimal pressure needed to achieve an improvement in heart rate should be used or if there is no response chest wall movement Longer breaths at lower pressure may be more effective in displacing alveolar fluid and establish-ing the resting lung volume in lungs with sufficient surfactant and may improve initial oxygenation However premature new-borns are obviously physiologically and anatomically less pre-pared for delivery than infants at term Over-inflation has been implicated in histological lung damage in animal models and high tidal volumes appear to be equally damaging whether given before or immediately after administration of surfactant How-ever the same effect is not seen if these excessive tidal volumes are delivered 15 min after administration of surfactant2526 It is now thought that both excess end expiratory volume and inad-equate end-expiratory volume may cause lung damage2728 In premature infants it would therefore seem sensible to use lower pressures of 20ndash25 cmH2O12 delivered in a controlled way to prevent over-inflation and to apply positive end-expiratory pres-sure (PEEP) to prevent damage from under-inflation PEEP also improves both lung compliance and gas exchange2930 Without PEEP the airways collapse during the expiratory phase in animal models of newborn resuscitation
If animal data can be extrapolated it would also seem appro-priate to give surfactant as soon as possible to premature babies in order to ameliorate damage2526
The majority of newborn infants requiring resuscitation will re-establish regular respiration after administration of a few breaths which may be due to Headrsquos paradoxical reflex by which the inflation triggers an inspiratory effort
VentilationOnce the lungs are aerated if the newborn remains apnoeic ventilation should be continued at 30ndash60 breathsmin avoiding hyperventilation and using the minimum pressure possible to maintain a heart rate greater than 100 beatsmin
Face mask the majority of infants who require ventilation receive it via a face mask This may be attached to a bagvalve system with a spring lsquoblow offrsquo system or a lsquoT-piecersquo with a set flow and pressure It is important to realize that the bagvalve system is flow sensitive and that the harder the operator presses the greater the flow and the higher the delivered pressure In fact 60 cmH2O can be achieved with vigorous squeezing of a self-inflating bag Therefore it may be advantageous that most opera-tors are unlikely to be as effective as they suppose in creating a seal with the mask31 This is a skill that requires tuition and prac-tice31 In delivering a set pressure T-piece systems such as the Tom Thumbcopy or Neopuffcopy perform better than any bagminusvalve system but require a gas supply There is no evidence that lung compliance can be assessed using any bag system
Continuous airway pressure case series have suggested that early or delivery room use of continuous positive airway pres-sure (CPAP) in premature babies may reduce chronic lung dis-ease There have been two randomized trials of which one was a pilot study The data from the COIN trial do not show any advan-tage other than a reduction in intubation and surfactant use in the intervention group However an excess of pneumothorax
8 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
was also reported The Vermont Oxford Network and the SUP-PORT trials will provide further data but at present the delivery room use of CPAP cannot be widely recommended and should be limited to those units experienced in its use or taking part in research
Air or oxygen oxygen has been in widespread use for resuscita-tion at birth since the 1930s and even hyperbaric oxygen was seriously supported in the 1960s For many years there have been concerns about tissue damage from oxygen deprivation during and after resuscitation It became evident in the 1950s that unrestricted oxygen therapy could have serious conse-quences for future vision More recently concerns have been raised about potential adverse effects on respiratory physiology cerebral circulation and tissue damage from oxygen free radicals even during resuscitation A meta-analysis of four human studies demonstrated a reduction in mortality and no evidence of harm in infants resuscitated in air versus 100 oxygen3233 However there are several significant methodological concerns with these studies and the results should be interpreted with caution There is insufficient evidence to recommend any specific concentration of oxygen to be used for newborn resuscitation Monitoring the oxygen saturation of babies may be helpful but as yet there are no time-related normal target ranges and healthy term babies may take up to 10 min to achieve preductal oxygen saturation of greater than 95 and up to 60 min to achieve this postductally
There is therefore equipoise which would be open to an appropriate randomized controlled trial In the meantime the evidence only supports use of either 21 or 100 oxygen It is provoking to realize that if air had been in constant use since the 1930s there would be insufficient evidence for use of supple-mental oxygen
Circulation
Early resuscitation (temperature control airway breathing) provides oxygenated blood in the pulmonary arterioles which if returned to the heart causes the rate to increase34 If due to acidosis and hypoxia the circulation is ineffective then chest compressions may be needed They should be commenced when the heart rate remains below 60min despite effective airway and breathing management127 The best technique is using two hands to encircle the chest1 A ratio of three compressions to one breath is internationally accepted127 but has no evidence to support it Research has shown that neither compressions nor drugs will work in this situation without oxygenated blood so effective lung aeration and ventilation is essential A logical approach would be to fill the alveoli with air and to compress the chest until they are empty However training and teamwork require an agreed ratio which has therefore not changed since guidelines were first agreed internationally Success is assessed by an increase in heart rate which should therefore be assessed every 30 s Compressions stop when the spontaneous heart rate is greater than 60 beatsmin
In hypoxic newborn animal models successful resuscitation can restore cardiac output and blood pressure to levels above baseline within 5ndash10 min However it should be noted that there is a decline to 30 lower than basal levels within 2 h and that blood pressure is relatively spared suggesting an even greater
paeDiatRiCS anD CHilD HealtH 184 16
reduction in tissue perfusion This should be considered in the later care of any neonate who was hypoxic at birth
Drugs
Neonatal bradycardia at birth is almost always due to hypoxia plusmn acidosis and therefore drugs are rarely needed Adrenaline (epi-nephrine) is reported as being used in between 1 and 4 babies per 2000 births which is a large variation in practice Reported success is also variable and must be interpreted in light of this variation The use of drugs in extremely premature infants is con-troversial Some data suggested good outcomes for babies below 28 weeksrsquo gestation given adrenaline but these were flawed by high numbers of babies receiving resuscitative drugs some before the airway had been appropriately managed Audit data now suggest a poor outcome such that many clinicians would now council against the use of adrenaline and other drugs to resuscitate extremely premature newborn babies
Adrenaline (epinephrine)In 2003 a Cochrane review of randomized controlled trials involv-ing adrenaline use for resuscitation of neonates was unable to identify a single clinical trial35 Despite the lack of human neo-natal data animal models show the potential of adrenaline in asphyxial cardiac arrest and it is reasonable to use it when ade-quate ventilation and chest compressions have failed to increase the heart rate above 60 beatsmin Use 10ndash30 μgkg intrave-nously and preferably via an umbilical venous line The tracheal route cannot be recommended but if used it is likely that doses within this range will be ineffective and 100 μgkg might be tried However the safety of such doses has not been studied
BicarbonateThe use of bicarbonate has long been controversial but many of the concerns relate to the rapid correction of acidosis in neonates after resuscitation or the routine use of bicarbonate infusion nei-ther of which can be advocated There are no published human neonatal data to support its use although some exist from animal studies Animal data have also shown that the binding of adren-aline to receptors in the myocardium is significantly impaired by lactic acidosis and recent work on human lymphocyte beta-adrenergic receptors supports this view Whether this is also true of the more important alpha receptors is unknown In practice reversing intracardiac acidosis may improve myocardial function and assist in achieving a return of spontaneous circulation 1ndash2 mmolkg of bicarbonate may be given but this remains a contro-versial area
VolumeVolume expansion should only be given when it is suspected that the baby has suffered blood loss or the infant appears to be in shock (pale poor perfusion weak pulse) and has not responded adequately to other resuscitative measures If there is no history suggestive of blood loss shock is most likely to be due to myo-cardial dysfunction in which case fluids should be administered cautiously The most logical replacement fluid would be blood but in its absence isotonic crystalloid rather than albumin is the solution of choice given in 10 mlkg aliquots and observing the response Three randomized trials in neonates have shown
9 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
isotonic crystalloid to be as effective as albumin for the treat-ment of hypotension but none has examined either the relative or actual effectiveness in resuscitation A recent blinded randomized study comparing normal saline albumin or no volume expansion in a normovolaemic asphyxiated neonatal animal model showed that volume expansion was not beneficial and made a number of parameters worse36
NaloxoneNaloxone is not recommended as part of the initial resuscita-tion of newborns with respiratory depression Before it is given supporting ventilation should have restored the heart rate and colour The dose is 100 μgkg intravenously or intramuscularly Tracheal administration cannot be recommended Although administration of naloxone to neonates who have been exposed to maternal opioids during labour is a practice of long-standing it lacks the proper evidence of efficacy
Non-response to resuscitation
There are few more frightening situations professionally than applying the correct interventions in resuscitating or stabilizing a baby and getting no response Each stage must be adequately performed before moving onto the next and this requires regular reassessment When experienced help is needed at a newborn resuscitation it is usually the airway and ventilation that require correction If the heart rate does not increase this usually means that the lungs have not been successfully aerated In some cases however it may mean that the heart cannot respond as the cir-culation is inadequate In this situation the only way to check that the lungs have been successfully aerated is to see the chest move with ventilation or to obtain evidence of ventilation from a detector of exhaled carbon dioxide If you do not see chest movement after another five breaths the most likely cause is an obstructed airway either due to incorrect positioning or because the jaw has not been drawn forwards An oropharyngeal airway can be very helpful at this point especially in the term baby Only very occasionally is the airway blocked by mucus vernix blood or meconium but if the airway is guaranteed and there is no heart rate response or chest movement this should be sought by direct suction of the trachea even in the absence of any meconium staining of liquor Pneumothoraces can occur spontaneously after delivery but are rare at resuscitation carried out with pressure-limited devices Equally rare are diaphragmatic hernias that have not been diagnosed antenatally giving problems at resuscitation
If the chest is moving but the heart rate has not responded to resuscitation consider rare possibilities such as fetal blood loss pneumothorax or heart block (mothers with undiagnosed systemic lupus erythematosis delivered for fetal bradycardia) as possibilities With adequate ventilation there is no evidence of oxygen concentrations less than 100 being responsible for prolonged bradycardia or failure to respond although current practice would support increasing the delivered oxygen concen-tration if resuscitation had been commenced using air
Outcome
The prognosis for the full-term baby subjected to sudden acute asphyxia is usually good provided the episode does not last for
paeDiatRiCS anD CHilD HealtH 184 17
long Most babies resuscitated from primary apnoea have no sequelae secondary to the resuscitation Many babies who start to breathe again regularly within 20 min of the circulation being restored recover completely but it is rare for a baby who is still gasping after 30 min to recover
The prognosis for the preterm baby of less than about 34 weeksrsquo gestation subjected to severe acute anoxia is less predict-able This is because of the risk of secondary intraventricular haemorrhage or periventricular intracerebral haemorrhage andor infarction after even a relatively brief asphyxial episode espe-cially in the period immediately around birth
The effects of chronic hypoxia are also difficult to predict but a reasonably clear idea of the extent of the problem should be obtainable within 36ndash48 h of the original chronic asphyxial insult A mild short-lasting state of hyperexcitability usually car-ries a good prognosis even if there is seizure activity but more severe symptoms can be associated with permanent handicap This is seen especially in infants with encephalopathy requiring ventilation
REFERENCEs
1 Biarent D Bingham R Richmond S et al european Resuscitation
Council guidelines for Resuscitation 2005 Section 6 paediatric life
support Resuscitation 2005 67(suppl 1) S97ndashS133
2 international liaison Committee on Resuscitation part 7 neonatal
resuscitation Resuscitation 2005 67 293ndash303
3 Singh J Santosh S Wyllie J mellon a effects of a course in
neonatal resuscitation - evaluation of an educational intervention
on the standard of neonatal resuscitation Resuscitation 2006 68
385ndash389
4 palme-Kilander C methods of resuscitation in low-apgar-score
newborn infants - a national survey Acta Paediatr 1992 81
739ndash744
5 Kroll l twohey l Daubeney p et al Risk factors at delivery and
the need for skilled resuscitation Eur J Obstet Gynecol Reprod Biol
1994 44 175ndash177
6 Wyllie Jp Resuscitation of the newborn The Foundation Years
2007 3(4) 153ndash157
7 Richmond S ed newborn life Support Resuscitation at Birth
london Resuscitation Council 2006
8 Ceriani Cernadas Jm Carroli g pelligrine l et al the effect of timing
of cord clamping on neonatal venous hematocrit values and clinical
outcome at term a randomized controlled trial Pediatrics 2006
117 e779ndashe786
9 mercer JS Vohr BR mcgrath mm padbury JF Wallach m oh W
Delayed cord clamping in very preterm infants reduces the incidence
of intraventricular hemorrhage and late-onset sepsis a randomized
controlled trial Pediatrics 2006 117 1235ndash1242
10 Dahm lS James lS newborn temperature and calculated heat loss
in the delivery room Pediatrics 1972 49 504ndash513
11 Stephenson J Du J tk o the effect of cooling on blood gas
tensions in newborn infants J Pediatr 1970 76 848ndash852
12 gandy gm adamsons Jr K Cunningham n Silverman Wa James lS
thermal environment and acid-base homeostasis in human infants
during the first few hours of life J Clin Invest 1964 43 751ndash758
13 gluck l Kulovich mV eidelman ai et al Biochemical development
of surface activity in mammalian lung pulmonary lecithin synthesis
0 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
in the human fetus and newborn and etiology of the respiratory
distress syndrome Pediatr Res 1972 6 81ndash99
14 Vohra S Roberts RS Zhang B Janes m Schmidt B Heat loss
prevention (Help) in the delivery room a randomised controlled
trial of polyethylene occlusive skin wrapping in very preterm infants
J Pediatr 2004 145 750ndash753
15 owen CJ Wyllie Jp Determination of heart rate in babies at birth
Resuscitation 2004 60 213ndash217
16 orsquoDonnell Cp Kamlin Co Davis pg Carlin JB morley CJ Clinical
assessment of infant colour at delivery Arch Dis Child Fetal
Neonatal Ed 2007 92 F465ndashF467
17 international liaison Committee on Resuscitation part 13 neonatal
Resuscitation guidelines Circulation 2005 112(suppl 24)
iV188ndashiV195
18 leone ta Rich W Finer nn neonatal intubation Success of
pediatric trainees J Pediatr 2005 146 638ndash641
19 orsquoDonnell Cp Kamlin Co Davis pg morley CJ endotracheal
intubation attempts during neonatal resuscitation success
rates duration and adverse effects Pediatrics 2006 117
e16ndash21
20 Repetto Je Donohue pa-CpK Baker SF Kelly l nogee lm use of
capnography in the delivery room for assessment of endotracheal
tube placement J Perinatol 2001 21 284ndash287
21 gandini D Brimacombe JR neonatal resuscitation with laryngeal
mask airway in normal and low birth weight infants Anesth Analg
1999 89 642ndash643
22 esmail n Saleh m ali a laryngeal mask airway versus endotracheal
intubation for apgar score improvement in neonatal resuscitation
Egypt J Anesthiol 2002 18 115ndash121
23 Wiswell te gannon Cm Jacob J et al Delivery room management
of the apparently vigorous meconium-stained neonate results of
the multicenter international collaborative trial Pediatrics 2000
105 1ndash7
24 Vain ne Szyld eg prudent lm Wisewell te aguilar am Vivas ni
oropharyngeal and nasopharyngeal suctioning of meconium-stained
neonates before delivery of their shoulders multicentre randomised
controlled trial Lancet 2004 364 597ndash602
25 Bjorklund lJ ingimarsson J Curstedt t larsson a Robertson B
Werner o lung recruitment at birth does not improve lung function
in immature lambs receiving surfactant Acta Anaes Scand 2001 45
986ndash993
26 Bjorklund lJ ingimarsson J Curstedt t et al manual ventilation
with a few large breaths at birth compromises the therapeutic effect
of subsequent surfactant replacement in immature lambs Pediatr
Res 1997 42 348ndash355
paeDiatRiCS anD CHilD HealtH 184 17
27 taskar V John J evander e Robertson B Jonson B Surfactant
dysfunction makes lungs vulnerable to repetitive collapse and re-
expansion Am J Respir Crit Care Med 1997 155 313ndash320
28 muscedere Jg mullen JB gan K Slutsky aS tidal ventilation at low
airway pressures can augment lung injury Am J Respir Crit Care Med
1994 149 1327ndash1334
29 nilsson R grossman g Robertson B Bronchiolar epithelial lesions
induced in the premature rabbit neonate by short periods of artificial
ventilation Acta Pathol Microbiol Scand 1980 88 359ndash367
30 probyn me Hooper SB Dargaville pa et al positive end expiratory
pressure during resuscitation of premature lambs rapidly improves
blood gases without adversely affecting arterial pressure Pediatr
Res 2004 56 198ndash204
31 Wood Fe morley CJ Dawson Ja et al improved techniques
reduce face mask leak during simulated neonatal resuscitation
study 2 Arch Dis Child Fetal Neonatal Ed in press doi101136
adc2007117788
32 tan a Schulz a orsquoDonnell CpF Davis pg air versus oxygen for
resuscitation of infants at birth Cochrane Database Syst Rev 2004
(3) CD002273
33 Davis pg tan a orsquoDonnell Cp Schulze a Resuscitation of newborn
infants with 100 oxygen or air a systematic review and meta-
analysis Lancet 2004 364 1329ndash1333
34 Dawes g Fetal and neonatal physiology Chicago year Book
publisher 1968 p 141ndash159
35 Ziino aJa Davies mW Davis pg epinephrine for the resuscitation
of apparently stillborn or extremely bradycardic newborn infants
Cochrane Database Syst Rev 2003 (2) CD003849
36 Wyckoff m garcia D margraf l perlman J laptook a Randomized
trial of volume infusion during resuscitation of asphyxiated neonatal
piglets Pediatr Res 2007 61 415ndash420
Practice points
bull Resuscitation at birth is different from that at all other times
of life
bull a standard approach can be applied to most newborn
resuscitation
bull guidelines are based on a rigorous evaluation of evidence
where possible
bull evidence is sparse but evolving
bull most preterm babies require stabilization rather than
resuscitation
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Acidndashbase physiology and blood gas interpretation in the neonateSusern tan
morag Campbell
Abstractacidndashbase balance describes the complex processes that work to main-
tain a stable extracellular pH for optimal cellular function the process
of balancing the production and neutralization of tissue acid provides a
great challenge for newborn infants who have significantly higher rates
of acid production than adults Factors which help maintain a stable
acidndashbase balance include buffers the respiratory system and renal sys-
tem Both intracellular and extracellular buffers resist changes in pH
the most important extracellular buffer system for maintaining stable
pH is the bicarbonate system in response to acidosis or alkalosis the
respiratory system balances the production of acid with the clearance
of Co2 by altering respiratory rate the kidneys provide a delayed but
sustained response to pH imbalance by excreting either acidic or alkaline
urine in response to systemic acidosis and alkalosis respectively in sick
premature infants these systems have a limited capacity completely to
control pH this review discusses the physiology of the three systems
which control acidndashbase balance patterns of clinical abnormalities in
acidndashbase status and their underlying causes are discussed We present
a systematic approach to blood gas analysis and interpretation in new-
born infants
Keywords acidosis alkalosis bicarbonate bloodndashgas analysis
metabolic pH
Introduction
Blood gas analysis is a routine procedure performed on newborn babies receiving respiratory support in the neonatal intensive care The combination of invasive and non-invasive assessment of ventilation and oxygenation enables clinicians appropriately to modify respiratory care according to each individual babyrsquos rapidly changing clinical status
Understanding the fundamentals of acidndashbase balance helps us to use blood gas analysis not only to assess respiratory sta-tus but also to provide information on metabolic status and the adequacy of tissue perfusion
Susern Tan MBBS MRCP is Clinical Fellow at the Neonatal Intensive Care
Unit 6th Floor North Wing St Thomasrsquo Hospital London SE1 7EH UK
Morag Campbell MBChB MRCP is Consultant Neonatologist at the
Neonatal Intensive Care Unit 6th Floor North Wing St Thomasrsquo
Hospital London SE1 7EH UK
paeDiatRiCS anD CHilD HealtH 184 17
What is understood by acid-base balance
Acidndashbase balance refers to the complex physiological processes used by the body to maintain a stable extracellular pH1 A serum pH within the range of 735ndash745 provides the ideal environment for cellular metabolism Maintaining a stable pH is critical as the metabolic activity of proteins is pH dependent and small changes in hydrogen ion (H+) concentration can potentially alter physio-logical function
Acids are substances that yield free H+ in solution while a base accepts H+ and in solution combines with an acid to neu-tralize it In the normal metabolic state H+ are continuously pro-duced and neutralized to maintain a steady pH balance12 The rate of H+ production is two to three times higher in neonates because of their rapid growth rates and increased acid production from protein turnover and bone mineralization The challenge of maintaining a stable pH through processing and neutralizing H+ is therefore greatest in newborn infants
Using exact values of H+ concentration to assess acidndashbase status is cumbersome and it is more commonly expressed as pH defined by the equation
pH = minuslog H+
Maintaining acidndashbase balance
The balance between production and excretion of acids in the body is controlled by buffer systems which have an immediate effect and by the respiratory and the renal systems
Buffer systemsBuffer solutions resist change in pH when acid or alkali is added due to their capacity to absorb or give up H+ The three main buffer systems in the body are the bicarbonate phosphate and protein systems1ndash3 The protein and phosphate buffer systems are intracellular and act as lsquosinksrsquo for extracellular H+ which are exchanged with intracellular potassium (K+) and sodium ions (Na+) In an acute metabolic acidosis hyperkalaemia may develop due to this H+ exchange4
The bicarbonate buffer system is extracellular and consists of a mixture of carbonic acid (H2CO3) and sodium bicarbon-ate (NaHCO3) This buffer system helps maintain a stable pH by soaking up excess H+ with HCO3
minus which in solution forms carbonic acid (H2CO3) Carbonic acid is a weak acid and readily dissociates to give CO2 which is transported in dissolved form to the lungs for excretion
H+ + HCO3minus harr H2CO3 harr H2O + CO2
The bicarbonate system therefore completes the neutraliza-tion of excess H+ and a stable plasma pH is maintained The relationships between pH HCO3
minus and CO2 in this system are described by the HendersonndashHasselbalch equation15
pH = 61 + log HCO3minus003 times CO2
where 61 is the log of the dissociation coefficient of carbonic acid and 003 the solubility of CO2 in plasma Buffers are most potent when there are equal amounts of H+ and HCO3
minus in solution The
2 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
bicarbonate system is not a potent buffer however as HCO3minus
and CO2 are readily altered by the body this system plays a very powerful role in pH homeostasis15
Respiratory regulationThe respiratory system adapts within minutes to hours as part of the acute response to acidosis This system modifies pH by balancing production of H+ with ventilatory clearance of CO2
H+ directly stimulates chemoreceptors in the respiratory cen-tre of the brainstem producing an increase in respiratory rate26 The response to respiratory acidosis is very rapid as CO2 easily diffuses across the bloodndashbrain barrier however in metabolic acidosis compensation is delayed until plasma bicarbonate fully equilibrates with cerebrospinal fluid (CSF) bicarbonate There is an inverse relationship between alveolar ventilation and partial pressure of dissolved carbon dioxide (PaCO2) a reduction in alveolar ventilation raises PaCO2 and decreases pH Changes in pH therefore affect alveolar ventilation and conversely changes in alveolar ventilation cause significant changes in pH
Renal regulationThe kidneys provide a delayed but sustained response to acidndashbase imbalances by excreting either acidic or alkaline urine In full-term and preterm babies the capacity for acid excretion and bicarbonate reabsorption is reduced as glomerular filtration rates are low and tubular function immature7 Renal function matures with gestation postnatal age and glucocorticoid and thyroid hormones78 Due to their limited capacity to preserve HCO3
minus newborn infants have lower serum bicarbonate levels and are predisposed to acidosis7
Bicarbonate is not effectively reabsorbed due to its size and electrical charge Instead intraluminal HCO3
minus combines with secreted H+ in tubular luminal fluid to produce carbonic acid which dissociates to give H2O and CO2 This CO2 diffuses into tubular cells combines with intracellular H2O and forms carbonic acid which liberates HCO3
minus and H+ HCO3minus is then
recovered to the circulation by exchange for chloride ions (Clminus) through the basal cell membrane247
Renal acid secretion occurs at all sites except the loop of Henle Primary active transport accounts for 5 and secondary for the remaining 95 of total H+ excretion Secondary trans-port involves an exchange between luminal Na+ and intracel-lular H+ Both ions bind to a membrane transport protein The Na+ concentration gradient between the tubular lumen and cells enables Na+ drag into the cell which generates energy to fuel active H+ excretion into the tubular lumen1ndash47
Quantifying acidosis
Standard base excess is a calculated value derived from PaCO2 and pH It is expressed as the mmollitre of base above or below normal buffer bases required to correct the pH to 74 at a PaCO2 of 40 mmHg A negative base excess or base deficit indicates an acidosis while a positive base excess indicates a relative alkalosis15
Anion gap is the measured difference between anions and cations in the blood
Anion gap = (Na+ + k+) minus (HCO3+Clminus)
paeDiatRiCS anD CHilD HealtH 184 17
Calculation of the anion gap enables clinicians better to define the underlying cause of a metabolic acidosis9 The common causes of an increased anion gap acidosis in neonates include lactic acidosis due to tissue hypoperfusion and hypoxia it may also be seen with certain inborn errors of metabolism and in uraemia910 The anion gap can help distinguish between the rela-tively benign non-anion gap hyperchloraemic acidosis seen in premature infants and a pathological lactic acidosis due to poor end-organ perfusion1011
Strong ion theory
Stewart described a complex acidndashbase model which proposed that H+ concentration results from the dissociation of water which is influenced by PaCO2 the strong ion difference and plasma weak acids12
Strong ions are ions that dissociate at normal body pH and include Na+ K+ and Clminus Weak acids in plasma which contrib-ute include albumin inorganic phosphate and plasma proteins their concentrations do not change with pH and are therefore a constant The effect of these factors and other unmeasured tissue ions on acidndashbase status can be quantified by the calculation of the strong ion gap (SIG)112 In the neonatal unit it is perhaps more important that we consider how principles of this model may relate to acidndashbase status rather than fully to quantify the SIG Theoretically low albumin and phosphate levels which fre-quently occur in premature infants by reducing the concentra-tion of weak acids can produce a relative alkalosis while high phosphate levels in renal failure may contribute to acidosis
Tissue oxygenation
Oxygenation is closely linked to acidndashbase status as optimal cel-lular function requires oxygen to fuel aerobic metabolism and produce energy In hypoxic conditions anaerobic metabolism predominates which is energy inefficient and results in a lactic acidosis1011
Tissue oxygen availability is related to regional blood flow haemoglobin level and haemoglobin oxygen affinity Arterial blood gases measure the partial pressure of dissolved oxygen (PaO2) which represents a small component of total oxygen con-tent the majority being transported bound to haemoglobin The relationship between percentage haemoglobin saturation (SaO2) and PaO2 is described by the sigmoidal oxyhaemoglobin disso-ciation curve which enables us to relate the two measures to each other235 The affinity of haemoglobin for oxygen is altered by local tissue factors Increases in temperature H+ PaCO2 and 23-diphosphoglycerate (DPG) levels shift the oxyhaemoglobin dissociation curve to the right reducing affinity for oxygen Decreases in temperature H+ PaCO2 and 23-DPG levels shift the curve to the left increasing oxygen affinity1ndash35 In the body haemoglobin oxygen affinity continuously changes increasing in the lungs to enable efficient oxygen uptake and decreasing at tissue level to provide efficient oxygen delivery to metabolically active tissues
Avoiding both hypoxia and hyperoxia is important in the neo-natal unit as deleterious effects of hypoxia are seen in infants with pulmonary hypertension1314 while hyperoxia is associated with an increased incidence of retinopathy of prematurity1516
3 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Clinical acidndashbase imbalances
Clinical acidndashbase imbalances can be respiratory metabolic or a mixture of both These abnormalities may be corrected by the acidndashbase regulatory mechanisms in the body in an attempt to maintain normal pH (Figure 1)
Respiratory acidosisThis occurs when any disorder leads to decreased alveolar ventilation Common causes of respiratory acidosis are listed in Table 1 Reduced respiratory clearance of CO2 means more dissolved CO2 accumulates in the plasma leading to increased production of carbonic acid and H+ Through chemoreceptor stimulation respiratory acidosis rapidly alters ventilation in an attempt to reduce CO226 Chemoreceptor mediated ventila-tory increases may only partly adjust in premature infants with underlying lung disease In babies with a sustained respiratory acidosis eg in chronic lung disease then metabolic compen-sation occurs through increased renal excretion of H+ and reabsorption of HCO3
minus slowly restoring pH to around 80 of normal47
paeDiatRiCS anD CHilD HealtH 184 17
The management of PaCO2 levels in infants receiving mechan-ical ventilation has important clinical implications Premature babies have impaired cerebral autoregulation17 and adverse neurological sequelae are reported in association with high PaCO2 levels18ndash20 Ventilation strategies which advocate lsquoper-missive hypercarbiarsquo have been developed to minimize airways damage from mechanical ventilation21 Published data suggest pulmonary benefits however the safe level of PaCO2 remains to be defined in premature infants2021
Respiratory alkalosisThis occurs when more CO2 is excreted than is produced by the body Pathological conditions leading to respiratory alkalosis are rare Hyperventilation in the neonatal setting is often iatrogenic or may be due to disorders in brainstem control of breathing including hypoxicndashischaemic encephalopathy or primary central nervous system abnormalities (see Table 1)
If respiratory alkalosis is sustained it may be compensated for by reduced reabsorption of filtered bicarbonate Reported adverse associations of low PaCO2 include periventricular leuco-malacia and intraventricular haemorrhage1922
K+
H+
Overventilation
CO2 + H2O harr H2CO3 harr H+ + HCO3ndash
Bicarbonate Buffer
Intracellular Buffer
uarr H+ excretionuarr HCO3
ndash absorption
uarr buffered H+
(NH4+ H2PO4
ndash)uarr ventilation rate
RespiratoryAcidosis
MetabolicAcidosis
darr CO2and uarr pH
RespiratoryAlkalosis
MetabolicAlkalosis
darr H+ anduarr pH
darr ventilation rate
uarrCO2
and darr pH
darr H+ excretiondarr HCO3
ndash absorption
uarrH+ and
darr pH
Brain
Brain
Intracellular Buffer
H+
K+
Sepsis
HypoxiaRDS
Metabolismand growth
Diuretics
Airwayobstruction
Neuromuscularproblems
IEM
Gastric losses
+ +
ndash -
Renal BufferRespiratory Buffer
Figure 1 mechanisms for regulation of extracellular pH iem inborn errors of metabolism RDS respiratory distress syndrome
4 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Common causes of acidndashbase imbalances
pH PCO2 H2CO3 Base excess Common neonatal causes
Respiratory acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
uarr normal normal bull upper airway obstruction choanal atresia
pierre-Robin sequence
bull lung abnormalities respiratory distress
syndrome transient tachypneoa of
newborn pneumonia meconium aspiration
syndrome pulmonary hypoplasia
congenital pulmonary malformations
bull Central hypoventilation hypoxic-ischaemic
encephalopathy intracranial haemorrhage
bull neuromuscular insufficiency congenital
myopathies congenital neuropathies
bull iatrogenic inadequate ventilatory settings
Compensated lower limit
of normal
uarr uarr gt+3
metabolic acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
normal darr ltminus3 increased anion gap
bull lactic acidosis sepsis hypoperfusion
shock necrotizing enterocolitis
bull inorganic acidosis inborn errors of
metabolism renal failure
normal anion gap
bull increased gastrointestinal H2Co3 losses
ileostomy diarrhoea
bull Renal tubular acidoses
Compensated lower limit
of normal
darr darr ltminus3
Respiratory alkalosis Uncompensated gt 745 darr normal normal bull iatrogenic excessive ventilatory settings
bull Compensatory hyperventilation hypoxic-
ischaemic encephalopathy
Compensated higher limit
of normal
darr darr ltminus3
metabolic alkalosis Uncompensated gt 745 normal uarr gt+3 bull gastric losses vomiting non-replacement
of excessive nasogastric aspirates
bull thiazide and loop diuretics
bull Hypokalaemia
Compensated higher limit
of normal
uarr uarr gt+3
Table 1
Metabolic acidosisThis frequently affects infants in the neonatal unit and has many causes1011 (see Table 1) There may be overproduction of tissue acid impaired acid clearance gastrointestinal loss of bicarbonate or an exogenous increased acid load eg chloride total paren-teral nutrition (TPN) or albumin1ndash323
Calculation of the anion gap to distinguish an increased anion gap acidosis from a non-anion gap acidosis is important both for treatment and prognosis1011 Acidosis stimulates respiratory compensation but this is limited in unstable infants Similarly renal compensation with improved HCO3
minus conservation is con-strained by tubular immaturity Treatment of the acidosis should be directed at the underlying cause eg hypoxia hypotension or excess Clminus rather than by administration of base
Metabolic alkalosisThis is unusual in neonates and is most frequently seen in infants with chronic lung disease or heart failure who are receiving diuretics Diuretics cause alkalosis by increasing renal fluid and Na+ losses An active process to reabsorb Na+ occurs in tubule cells which through enhanced H+ secretion and HCO3
minus reab-sorption produce alkalosis27
paeDiatRiCS anD CHilD HealtH 184 17
Metabolic alkalosis may also occur with excessive loss of gas-tric contents eg protracted vomiting or inadequate replacement of nasogastric aspirates (see Table 1)
Interpreting blood gases
Blood gas measurements can provide important diagnostic and prognostic information and a systematic approach to blood gas analysis is described in Table 2 The clinical management of infants with abnormal gases requires a good understanding of acidndashbase physiology and tissue oxygenation and an apprecia-tion of factors which may affect the reliability of samples
Arterial blood sampling is the gold standard however indwelling arterial catheters and arterial stab samples are usually restricted to infants who are critically ill or those who require sig-nificant ongoing intervention Gases are most frequently measured in capillary or venous samples which correlate well with arterial samples for PaCO2 pH and base excess in babies and children receiving intensive care These correlations however are not valid in infants with peripheral vasoconstriction and hypotension2324
Non-invasive monitoring techniques may enable us to reduce the frequency of blood gas sampling Transcutaneous monitoring
5 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
A systematic approach to blood gas analysis
1 Collect the relevant information
bull type of gas ndash capillary or arterial
bull Current respiratory support ndash document level
bull transcutaneous Co2 and Sao2 levels
bull Clarify no significant clinical events before sampling
2 pH accept a range between 730 and 745 in newborn
babies this is lower than in older children is there an
alkalosis (pH gt 745) or an acidosis (lt 730)
3 Co2 aim for a range between 45 and 65 kpa a paCo2 level
more than 65 kpa suggests inadequate alveolar ventilation
while less than 45 kpa suggests hyperventilation Correlate
values with non-invasive measures
4 o2 Can only be assessed from arterial gases aim for pao2
between 60 and 80 kpa Correlate results with pulse
oximetry levels
5 HCo3 and base excess normal HCo3 level is between 20 and
24 mmollitre and bases excess +3 to minus3
6 anion gap look at the anion gap and lactate to help identify
the cause of an acidosis normal lactate levels should be less
than 2 mmollitre
7 Respiratory or metabolic compensation look at the pH and
assess whether it is appropriate for the Co2 level or is there
evidence of compensation
8 interpret use both the clinical history and blood gas
findings to help you identify the primary problem aim your
management at treating the underlying cause
9 Reassess if clinical management changes have been made
repeat the blood gas after an appropriate time interval to
ensure improvement
Table 2
provides a highly accurate and reliable method for measuring PaCO2 through the skin it can however be technically difficult may cause tissue damage and is of limited reliability when peripheral perfusion is reduced25 Continuous end-tidal CO2 measurements correlate well with arterial CO2 values in patients with normal ventilation and perfusion however in babies with lung disease alveolar collapse small tidal volumes and rapid respiratory rates can make these measurements unreliable26 Despite its limitations transcutaneous monitoring provides the best method for CO2 trend monitoring in the neonatal intensive care unit (NICU)25
Oxygen saturation levels can be continuously measured non-invasively using pulse oximetry While oximetry is easy to perform and accurate on occasion SaO2 levels obtained may be unreliable when tissue perfusion is poor or with movement artefact SaO2 monitoring is highly sensitive at detecting hypoxia but is limited in detecting hyperoxia as at levels more than 90 small changes in SaO2 may result in unacceptably large increases in PaO227 It is therefore essential that SaO2 alarm limits are set for all neonates receiving respiratory support to detect hypoxia and prevent hyperoxia1627
Continuous non-invasive monitoring provides invaluable information when managing complex infants in the NICU but it does not replace the need for regular blood gas analysis
paeDiatRiCS anD CHilD HealtH 184 17
ReFeRenCeS
1 Kellum Ja Determinants of blood pH in health and disease
Crit Care 2000 4 6ndash14
2 Quigley R Baum m neonatal acid base balance and disturbances
Semin Perinatol 2004 28 97ndash102
3 Brouillette Rt Waxman DH evaluation of the newbornrsquos blood gas
status Clin Chem 1997 43 215ndash221
4 Chan JC acid-base disorders and the kidney Adv Pediatr 1983 30
401ndash471
5 Siggaard-andersen o the pH-log pCo2 blood acidndashbase nomogram
revised Scand J Lab Invest 1962 14 598ndash604
6 Saetta m mortola Jp interaction of hypoxic and hypercapnic stimuli
on breathing pattern in the newborn rat J Appl Physiol 1987 62
506ndash512
7 Baum m Quigley R postnatal renal development in Seldin DW
giebisch g eds the kidney physiology and pathophysiology new
york lippincott Williams and Wilkins 2000 p 703ndash726
8 ortiz la Quan a Weinberg a et al effect of prenatal
dexamethasone on rat renal development Kidney Int 2001 59
1663ndash1669
9 gabow pa Kaehny WD Fennessey pV goodman Si gross pa
Schrier RW Diagnostic importance of an increased serum anion gap
N Engl J Med 1980 303 854ndash858
10 lorenz Jm Kleinman li markarian K oliver m Fernandez J Serum
anion gap in the differential diagnosis of metabolic acidosis in
critically ill newborns J Pediatr 1999 135 751ndash755
11 Deshpande Sa platt mp association between blood lactate and
acid-base status and mortality in ventilated babies Arch Dis Child
1997 76 F15ndash20
12 Stewart pa modern quantitative acid-base chemistry Can J Physiol
Pharmacol 1983 61 1444ndash1461
13 Dakshinamurti S pathophysiologic mechanisms of persistent
pulmonary hypertension of the newborn Pediatr Pulmonol 2005
39 492ndash503
14 mourani pm ivy DD gao D abman SH pulmonary vascular
effects of inhaled nitric oxide and oxygen tension in
bronchopulmonary dysplasia Am J Respir Crit Care Med 2004
170 1006ndash1013
15 Deulofeut R Critz a adams-Chapman i Sola a avoiding hyperoxia
in infants le 1250 g is associated with improved short- and long-
term outcomes J Perinatol 2006 26 700ndash705
16 Chow lC Wright KW Sola a Can changes in clinical practice
decrease the incidence of severe retinopathy of prematurity in very
low birth weight infants Pediatrics 2003 111 339ndash345
17 Boylan gB young K panerai RB Rennie Jm evans DH Dynamic
cerebral autoregulation in sick newborn infants Pediatr Res 2000
48 12ndash17
18 Kaiser JR gauss CH pont mm Williams DK Hypercapnia during
the first 3 days of life is associated with severe intraventricular
hemorrhage in very low birth weight infants J Perinatol 2006 26
279ndash285
19 Fabres J Carlo Wa phillips V Howard g ambalavanan n Both
extremes of arterial carbon dioxide pressure and the magnitude of
fluctuations in arterial carbon dioxide pressure are associated with
severe intraventricular hemorrhage in preterm infants Pediatrics
2007 119 299ndash305
20 thome uH Carroll W Wu tJ et al outcome of extremely preterm
infants randomized at birth to different paCo2 targets during the
first seven days of life Biol Neonate 2006 90 218ndash225
6 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
21 Carlo Wa Stark aR Wright ll et al minimal ventilation to prevent
bronchopulmonary dysplasia in extremely-low-birth-weight infants
J Pediatr 2002 141 370ndash374
22 okumura a Hayakawa F Kato t et al Hypocarbia in preterm
infants with periventricular leukomalacia the relation between
hypocarbia and mechanical ventilation Pediatrics 2001 107
469ndash475
23 peters o Ryan S matthew l Cheng K lunn J Randomised
controlled trial of acetate in preterm neonates receiving parenteral
nutrition Arch Dis Child 1997 77 F12ndash15
24 yildizda D yapiciolu H yilmaz Hl Sertdemir y Correlation of
simultaneously obtained capillary venous and arterial blood gases
of patients in a paediatric intensive care unit Arch Dis Child 2004
89 176ndash180
25 aliwalas ll noble l nesbitt K et al agreement of carbon
dioxide levels measured by arterial transcutaneous and end tidal
methods in preterm infants 28 weeks gestation J Perinatol 2005
25 26ndash29
26 Hagerty JJ Kleinman me Zurakowski D et al accuracy of a new
low-flow sidestream capnography technology in newborns a pilot
study J Perinatol 2002 22 219ndash225
paeDiatRiCS anD CHilD HealtH 184 17
27 poets CF Wilken m Seidenberg J Southall Dp von der Hardt H
Reliability of a pulse oximeter in the detection of hyperoxemia
J Pediatr 1993 122 87ndash90
Practice points
bull a stable extracellular pH is important for optimal cellular
functioning
bull abnormalities in acidndashbase balance are regulated by buffer
systems and the respiratory and renal tract
bull maintaining a stable pH is challenging for newborn babies
due to their high rates of acid production and immature
regulatory mechanisms
bull arterial or capillary blood gases provide an effective way to
monitor acidndashbase balance in newborns
bull Blood gases should be analysed in a structured manner
assessing pH and then respiratory and metabolic components
bull the treatment of acidndashbase abnormalities should be directed
at the underlying problem not merely at correcting pH
7 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Recognition and management of neonatal seizuresmalcolm levene
AbstractSeizures are the most common major manifestation of central nervous
system dysfunction in the newborn there are many causes but perina-
tal asphyxia and haemorrhagicinfarction lesions account for about 75
there is now considerable evidence that frequent but short seizures in
the neonate affect subsequent neurodevelopmental outcome Studies
using eeg or modified continuous tracing of eeg activity (aeeg or CFm)
have shown that there is often electroconvulsive dissociation this re-
fers to poor correlation between electrical seizures and clinical seizures
Commonly used anticonvulsants appear to increase electroconvulsive
dissociation effective management of neonatal seizures has proved very
disappointing and less than 50 of seizures are abolished by first-line
anticonvulsant medication (phenobarbitone or phenytoin) Drugs such
as midazolam and lidocaine may further reduce seizures but require
more evaluation the challenge is to assess new and more effective anti-
convulsants which are themselves associated with little neurotoxicity
Keywords antiepileptic drugs eeg neonatal seizures neurodegeneration
Convulsions are the most common major neurological sign seen in newborn infants and their incidence estimated from large population studies is 26 per 1000 live births1 Premature infants are over four times more likely to have convulsions than full-term infants12 Neonatal status epilepticus (continuous seizure activity lasting 30 min or more) diagnosed clinically is rare and accounts for only 5 of infants with seizures1 although this is now recognized more frequently as the result of continuous EEG monitoring3
Neonatal convulsions are described as presenting in a num-ber of different ways and various seizure types can be seen in the same baby over a number of hours The frequencies of the various patterns of seizure activity are given in Table 1 In very premature babies and to a lesser extent in term infants minor movement abnormalities may be difficult to identify as subtle seizures These include lip smacking tongue thrusting mouth-ing pedalling type movements of the lower limbs or swimming movements of the arms Apnoea can be a common manifesta-tion of subtle seizures The signs can be protean and vary from baby to baby or even in the same baby Virtually any stereotypic
Malcolm Levene MD FMedSc FRCPCH FRCH is Professor and Head of
Department of Paediatrics and Child Health at University of Leeds Leeds
and Honorary Neonatologist at Leeds General Infirmary Leeds UK
paeDiatRiCS anD CHilD HealtH 184 178
movement may be a manifestation of a seizure disorder in the newborn
Aetiology
The more carefully the fitting baby is investigated the more likely it is that a cause for the seizures will be found A number of recent papers have described the aetiology of neonatal con-vulsions after extensive investigations14 Tekgul et al4 recently studied a consecutive group of full-term infants with evidence of neonatal convulsions (recognized both clinically and on EEG) and reported their outcome Table 2 summarizes these data as well as risk of moderate or severe disability for each causative factor Perinatal asphyxia is the commonest cause for convul-sions in term infants with haemorrhagic or ischaemic lesions also being common
Overall the prognosis for the group of term babies with con-vulsions was good 72 had a favourable outcome Where asphyxia (hypoxicndashischaemic insult) is the cause of neonatal convulsions the outcome is poor in 50 The prognosis for neonatal convulsions when they were due to arterial or cere-brovenous infarction or intracranial haemorrhage was generally good Individually inborn errors are a very rare cause of neo-natal convulsions but in view of the treatable nature of some of these it is essential that these be considered and investigated appropriately5
Patterns of seizure activity in the newborn
Movement pattern Frequency ()
Clonic 50
tonic 20
Subtle 10ndash35 depending on maturity
myoclonic 5
Table 1
Cause incidence and outcome of neonatal convulsions in term infants14
Aetiological factor Incidence () Poor outcome ()
asphyxia 38ndash40 50
Cerebral arteriovenous
infarction
20 0
intracranial haemorrhage 12ndash20 13
Congenital cerebral anomaly 5ndash10 100
Hypoglycaemiahypocalcaemia 3ndash19
infection 3ndash20
inborn error of metabolism 1
unknown cause 10ndash13 0
Refers to moderate and severe neurodevelopmental abnormalitynumbers too small to make meaningful predictions
Table 2
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Controversies in the clinical management of neonatal seizures
In recent years we have learnt much more about the neurobi-ology of seizures and their effect on the developing brain The neonatal brain is in a neurophysiologically hyperexcitable state compared to the more mature brain and therefore is more prone to seizure activity This is due largely to a relative excess of GABA neuroreceptors GABA receptors are usually inhibitory but in the immature brain they have a paradoxically excitatory effect This changes at about term in primates and with progressive develop-ment they adopt a neuroinhibitory role6
The propensity to seizures in the neonatal brain makes resolv-ing the balance of risks between continuing seizure activity on the one hand against potentially adverse effects of therapy on the other a very important equation Added to this is the problem of accurately diagnosing neonatal seizures and whether commonly used anticonvulsants are successful in controlling them
These conundrums can be posed as a series of challenging questions which are discussed below
Do neonatal convulsions cause brain injuryConvulsions are a sign of neurological compromise and may indi-cate significant underlying structural brain damage or biochemi-cal disturbance which may cause further brain damage in its own right There has been considerable debate about the scale of the disability that convulsions cause the immature brain over and above that due to the underlying cause Most of our knowledge comes from studies in rodents and these have provided some tentative answers to this question
Seizures in the mature brain lead to neuronal necrosis but studies in very young rat pups whose brain development is somewhat similar to full-term infants have shown that a series of five brief seizures on five successive days does not cause struc-tural neuronal damage but does produce morphological changes in hippocampal neurones and worryingly deficits in the rat learning and visual spatial memory function in adolescent and adult life7 A single prolonged neonatal convulsion in similarly immature rats does not produce any functional effects8 Others have shown that following priming of the neonatal rat brain by short seizures as described above a further insult comprising induction of status epilepticus in the same rats at an older age causes neuronal necrosis9 This has been referred to as the lsquotwo hit hypothesisrsquo10
A more specific question is does seizure activity in an already significantly compromised brain cause additional neuropathol-ogy Wirrell et al11 studied a series of immature rat pups with the induction of an hypoxicndashischaemic (asphyxial) insult fol-lowed by either chemically-induced fits or a control sham pro-cedure In the more severely asphyxiated animals the degree of brain damage was increased significantly in those that had the additional burden of induced seizures
In summary these studies show that the immature brain is more resistant to short frequent post-seizure damage than the mature brain but despite resulting in no loss of neuronal numbers the function of the brain is permanently affected in later life In the asphyxiated brain seizures appear to have an additional adverse effect on brain damage Furthermore the immature brain that has been lsquoprimedrsquo by early seizures is more
paeDiatRiCS anD CHilD HealtH 184 179
vulnerable to status epilepticus later in life It would appear from these data that frequent seizures in the human infant should be stopped and this begs the question as to whether currently used anticonvulsants effectively control neonatal seizures
Can we rely on clinical versus EEG diagnosis of neonatal convulsionsTraditionally the diagnosis of neonatal convulsions has been made by observation and description of the frequency of abnor-mal movements EEG has been technically difficult in the hostile electrical activity of a neonatal intensive care environment and considerable expertise is required for analysis of the trace It is usually not practical to undertake traditional EEG recordings at the time the baby shows abnormal movements More recently various technological developments have allowed more direct investigation of neuronal electrical activity by either video-EEG or compressed recording of the amplitude integrated EEG (aEEG or CFM)
Rennie et al3 at Kingrsquos College Hospital London have under-taken extensive evaluation of video-EEG and have found that this technique detects many convulsions not recognized by a single channel aEEG or CFM trace Of 19 infants with evidence of convulsions on EEG only four were recognized on CFM but this may have been due to the observersrsquo lack of experi-ence with this technique In other centres that have developed appropriate expertise aEEG or CFM has proved more sensitive to the detection of seizures Video-EEG studies have also shown that many movements interpreted by experienced clinicians to be seizures are not associated with abnormal cortical activity Conversely many electrical seizures are not associated with abnormal movements This is referred to as electroconvulsive dissociation
In summary clinical observation alone to detect the fitting baby is unreliable in that it may either over-detect seizure activ-ity which is not present on EEG or under-detect clinical seizures in infants with EEG-proven convulsions The decision as to which babies to treat with antiepileptic drugs therefore becomes somewhat arbitrary
Do anticonvulsants stop neonatal seizuresAlthough neonatal seizures are common there are few random-ized controlled trials assessing the benefits of antiepileptic drugs (AEDs) in the treatment of this condition Phenobarbitone is the most widely used first-line AED and in an Australasian study 95 of neonatologists and paediatric neurologists used this drug as first-line management12 The most commonly used loading dosage is 20 mgkg but regimens of up to 40 mgkg have been recommended (Table 3)13 Four trials have evaluated the effect of phenobarbitone in abolishing neonatal seizures Two of these studies used EEG to monitor response to the drug1415 and one compared phenobarbitone with phenytoin15 In the latter study seizures were completely controlled in only 43 of babies and in the group where phenytoin was the first drug used com-plete seizure control was achieved in 45 This study switched babies from their first AED to the other if complete control was not obtained on EEG monitoring after exposure to first-line therapy In babies who had been given phenobarbitone as first-line therapy seizure control was only achieved in 57 after phenytoin was added In those given phenytoin first complete
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Dosage regimens for first- second- and third-line anticonvulsants in the neonatal period
Loading dose Second loading dose if first
unsuccessfulMaintenance dose
phenobarbitone 20 mgkg by slow iv injection 10 mgkg iv 25ndash5 mgkg od
phenytoin 20 mgkg iv over 20 min not recommended
midazolam 150ndash200 μgkg iv infusion 1 μgkgmin iv infusion increasing to 5 μgkgmin
until favourable response
lidocaine 2 mgkg iv over 10 min 6 mgkgh for 6 h iv then 4 mgkgh for 12 h then
2 mgkgh for 12 h
lorazepam 005ndash01 mgkg by slow iv injection
Diazepam 03ndash04 mgkg iv over 3ndash5 min
lidocaine should not be used if the infant has previously been treated with phenytoin
Table 3
seizure control was achieved with the adding of phenobarbitone in 62
Boylan et al14 assessed the efficacy of phenobarbitone (20ndash40 mgkg iv over 20 min) in 14 babies monitored by video-EEG in only four was there complete abolition of seizures and in the other 10 electroconvulsive seizure activity increased whereas clinical evidence of seizures reduced This has been termed elec-troclinical dissociation and anticonvulsant drug use in the new-born appears to increase this feature They also showed that the babies least likely to respond to the first-line AED are those with the most abnormal background EEG
Two studies have evaluated the use of phenobarbitone in babies who had sustained significant asphyxial insult at birth Hall et al13 compared high-dose phenobarbitone (mean 39 mgkg) versus standard dose (27 mgkg) and reported fewer convul-sions and a significant reduction of severe disability or death in the high dose group (RR 030 CI 010ndash093) A recent study from India16 of babies with hypoxicndashischaemic encephalopathy ran-domized 25 babies to phenobarbitone (20 mgkg loading dose) and compared them with 20 control babies Only 2 of 25 (4) in the phenobarbitone group developed convulsions compared with 8 of 20 (40) in the control group (p = 001) Because of the specific enrolment criteria (asphyxial insult) neither of these studies is strictly comparable to the studies by Painter et al15 and Boylan et al14 whose intention was to assess the efficacy of first-line anticonvulsant therapy on convulsions of any cause diagnosed either clinically or by EEG
Other anticonvulsants used as second- and third-line drugs have been subject to few studies in the newborn Midazolam is administered as a bolus followed by continuous infusion A recent study17 has shown that in 10 of 13 neonates given intravenous midazolam for status epilepticus control of electri-cal seizures was achieved within the first hour of treatment having been previously shown to be refractory to phenobarbi-tone treatment Some of these babies required a second bolus infusion of midazolam to obtain control of all electrographic seizures
In some parts of Europe lidocaine is used as a third-line anti-convulsant Malingre et al18 evaluated 20 infants refractory to
paeDiatRiCS anD CHilD HealtH 184 180
both phenobarbitone and midazolam and who were then given lidocaine by continuous infusion Lidocaine was effective in abolishing electroconvulsive seizures diagnosed by aEEG in 76 of the treatment courses studied No babies developed cardiac arrhythmias a previously reported complication of lidocaine in older patients As a result of pharmacokinetic studies the dosage regimen has been modified (see Table 3)
In summary phenobarbitone is effective in seizure control in less than 50 of babies and even when combined with phe-nytoin the efficacy of these drugs together remains poor More worrying is the observation that phenobarbitone tends to reduce clinically evident seizures thereby giving the clinician a false sense of security whilst having little or no effect on the num-bers of electroconvulsive disorders This has been summarized appropriately as lsquoafter all these years we still love what doesnrsquot workrsquo19 Both midazolam and lidocaine infusions appear to be effective in abolishing severe seizures in some infants resistant to phenobarbitone Lidocaine should not be given to babies previ-ously exposed to phenytoin for fear of a synergistic adverse effect on cardiac rhythm
Do antiepileptic drugs cause brain damageA riskndashbenefit analysis is needed to evaluate the efficacy of anticonvulsants in stopping neonatal seizures which is poor with standard anticonvulsants as discussed above against the risk of administering the anticonvulsant drugs themselves Phenobarbitone has been reported to have adverse effects on the developing brain including inhibition of brain growth20 neuronal toxicity21 and adverse behavioural and cognitive effects into adult life when administered to young animals22 Phenytoin shows unpredictable plasma levels and potential cardiotoxicity
Recent studies have shown an effect of AED exposure on the developing brain by causing neurodegeneration23 Phenytoin administration to immature rat pups at doses which produce serum levels similar to those achieved in human neonates was associated with widespread neuronal death as a result of apop-tosis (programmed cell death) Phenobarbitone had a similar effect when a dosage regimen similar to 40 mgkg was used and
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
this effect was maximal in the more immature brain Diazepam and clonazepam also resulted in a similar effect Midazolam and lidocaine were not tested in this study The combination of phenobarbitone or phenytoin with diazepam had a particularly profound effect on neurodegeneration
In summary recent data suggest that the commonly used AEDs for neonatal convulsions may in themselves cause neuro-degeneration due to apoptosis with lasting effects on develop-ment Many babies with neonatal convulsions are treated with at least two AEDs and this may produce more severe adverse effects than the seizures themselves
Practical management of neonatal seizures
Assimilation of these data and formulation of a rational policy is difficult when faced with a fitting neonate on an intensive care unit and pressure on the medical staff to lsquodo somethingrsquo but it is important to accept that sometimes doing nothing is preferable to using potentially dangerous drugs in a situation which does not warrant such intervention Many babies who have normal interseizure neurological clinical findings and whose seizures are relatively brief and infrequent probably do not need anticon-vulsant medication A normal or near-normal background EEG trace should reassure the clinician that anticonvulsants can be withheld
Some causes of neonatal convulsions are treatable such as meningitis hypoglycaemia hypocalcaemia and inborn errors of metabolism and each baby should be rapidly and carefully investigated for cause of the convulsions
In some babies clinical assessment of seizures is difficult ie when the baby is very sick small or paralyzed Sometimes it may be difficult to assess the significance of certain movement pat-terns Under these circumstances an EEG may prove to be very helpful In many units EEG is not available out of hours and a simple aEEG or CFM is strongly advised Modern instruments are very simple to apply and prolonged or frequent seizures should be identified with only moderate training The printout can be faxed to a more senior doctor if there is doubt as to what is shown on the trace
The balance of knowledge now is that frequent seizures cause additional damage to the developing brain and that treatment to abolish the seizures is warranted Unfortunately there is little evidence that the majority of seizures can be effectively termi-nated by current standard therapy Furthermore it appears that the more abnormal the background EEG the more difficult it is to control the seizures Nevertheless a written protocol for the management of neonatal convulsions is required on each unit Phenobarbitone and phenytoin remain the mainstay of treat-ment although their effectiveness is disappointing There is little to suggest that midazolam is more effective than lidocaine as third-line therapy but lidocaine is precluded if phenytoin has been previously used
In view of the anxiety as to the neurodegenerative effects on the immature brain of most anticonvulsants used in the neonatal period (particularly when multiple drugs are used) it is prefer-able to use only one drug to maximum dosage before introduc-ing a second In addition the duration of anticonvulsants should be minimized and the drugs stopped at the earliest opportu-nity It is my practice to stop anticonvulsants prior to discharge
paeDiatRiCS anD CHilD HealtH 184 18
from hospital if the baby is neurologically normal on clinical examination
REFEREnCES
1 Ronen gm penney S andrews W the epidemiology of clinical
neonatal seizures in newfoundland a population-based study
J Pediatr 1999 134 71ndash75
2 lanska mJ lanska DJ Baumann RJ et al a population-based study
of neonatal seizures in Fayette County Kentucky Neurology 1995
45 724ndash732
3 Rennie Jm Chorley g Boylan gB et al non-expert use of the
cerebral function monitor for neonatal seizure detection Arch Dis
Child Fetal Neonatal Ed 2004 89 F37ndashF40
4 tekgul H gauvreau K Soul J et al the current etoliologic profile
and neurodevelopmental outcome of seizures in term newborn
infants Pediatrics 2006 117 1270ndash1280
5 Surtees R Wolf n treatable neonatal epilepsy Arch Dis Child 2007
92 659ndash661
6 Ben-ari y Holmes gl effects of seizures on developmental
processes in the immature brain Lancet Neurol 2006 5 1055ndash
1063
7 Holmes gl gairsa Jl Chevassus-au-louis n et al Consequences of
neonatal seizures in the rat morphological and behavioral effects
Ann Neurol 1998 44 845ndash857
8 Stafstrom Ce Chronopoulos a thurber S et al age-dependent
cognitive and behavioural deficits following kainic-acid inducing
seizures Epilepsia 1993 34 420ndash432
9 Schmid R tandon p Stafstrom Ce et al effects of neonatal seizures
on subsequent seizure-induced brain injury Neurology 1999 53
1754ndash1761
10 Hoffmann aF Zhao Q Holmes gl Cognitive impairment following
status epilepticus and recurrent seizures during early development
support for the ldquotwo-hit hypothesisrdquo Epilepsy Behav 2004 5
873ndash877
11 Wirrell eC armstrong ea osman lD et al prolonged seizures
exacerbate perinatal hypoxic-ischemic brain damage Pediatr Res
2001 50 445ndash454
12 Carmo KB Barr p Drug treatment of neonatal seizures by
neonatologists and paediatric neurologists J Paediatr Child Health
2005 41 313ndash316
13 Hall Rt Hall FK Daily DK High-dose phenobarbital therapy in term
newborn infants with severe perinatal asphyxia a randomized
prospective study with three-year follow-up J Pediatr 1998 132
345ndash348
14 Boylan gB Rennie Jm pressler Rm et al phenobarbitone neonatal
seizures and video-eeg Arch Dis Child Fetal Neonatal Ed 2002 86
F165ndash170
15 painter mJ Scher mS Stein aD et al phenobarbital compared with
phenytoin for the treatment of neonatal seizures N Engl J Med
1999 341 485ndash489
16 Singh D Kumar p narang a a randomized controlled trial of
phenobarbital in neonates with hypoxic ischemic encephalopathy
J Matern Fetal Neonatal Med 2005 18 391ndash395
17 Castro Conde JR Borges H Domenech martinez e et al midazolam
in neonatal seizures with no response to phenobarbital Neurology
2005 64 876ndash879
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
18 malingre mm Van Rooij lgm Rademaker Cma et al Development
of an optimal lidocaine infusion strategy for neonatal seizures Eur
J Pediatr 2006 165 598ndash604
19 Sankar R painter mJ neonatal seizures after all these years we still
love what doesnrsquot work Neurology 2005 64 776ndash777
20 Diaz J Schain J Bailey Bg phenobarbital-induced brain growth
retardation in artificially reared rat pups Biol Neonate 1977 32 77ndash82
21 mattson RH phenobarbital toxicity in levy RH Dreifuss Fe
mattson RH et al eds antiepipeptic Drugs 3rd edn new york
Raven 1985 p 341ndash355
22 mikati ma Holmes gl Chronopoulos a et al phenobarbital
modifies seizure-related brain injury in the developing brain Ann
Neurol 1994 36 425ndash453
23 Bittigau p Sifringer m genz K et al antiepileptic drugs and
apoptotic neurodegeneration in the developing brain Proc Natl
Acad Sci U S A 2002 99 15089ndash15094
paeDiatRiCS anD CHilD HealtH 184 182
Practice points
bull the clinician needs to be aware that almost any repetitive
stereotype movement pattern can be a manifestation of
neonatal seizures
bull eeg is important in defining neonatal seizures
bull Frequent short-lived seizures have been shown to cause long-
term neurodevelopmental problems
bull Conventional anticonvulsant medication is ineffective in
abolishing neonatal seizures in greater than 50 of cases
bull there is evidence that exposure of the neonatal brain to
multiple anticonvulsants causes neuronal death
bull Future research is needed to evaluate more effective
anticonvulsants for treating this condition
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
Emotional support for families of sick neonatesMarina nicolaou
cristine Glazebrook
AbstractParents of sick neonates experience high levels of stress anxiety and
depression Most interventions with families of sick infants have focused
on fostering the motherndashinfant relationship through the provision of
information about infant developmental needs or through increased
motherndashinfant contact Many of these studies have reported improved
maternal well-being though there are some concerns about the scope
and practicality of large-scale interventions The few studies to have
prioritized emotional support for parents of sick neonates have pro-
duced encouraging results even interventions requiring relatively few re-
sources such as telephone support parent-to-parent support and group
support have been associated with reduced psychological morbidity for
parents The needs of parents can change throughout their infantrsquos hos-
pitalization and not all want or benefit from the provision of additional
support Thus neonatal intensive care units should aim to provide a
varied flexible and sustainable programme of support options Further
research should focus on the needs of fathers
Keywords mental health neonatal intensive care parents
The admission of an infant to neonatal care is acknowledged to be a source of considerable distress for families This review aims to explore evidence for the psychological impact on families of having an infant in neonatal intensive care and to identify evi-dence for the effectiveness of interventions to promote parental well-being It will conclude with recommendations for strategies to support parents of vulnerable infants and suggestions for fur-ther research
Psychological impact of neonatal care for parents
The majority of research examining the effect on parents of having a sick neonate has focused on families of premature or low birthweight infants Such research has found that parents with a sick neonate exhibit high levels of stress compared to normative samples and to parents of healthy full-term infants1 Singer et al2 examined the stress experienced by mothers of high-risk very low birthweight (VLBW) low-risk VLBW and term
Marina Nicolaou MPhil is a Teaching Assistant at the School of
Community Health Sciences University of Nottingham Nottingham UK
Cristine Glazebrook PhD is a Professor of Health Psychology at the School
of Community Health Sciences University of Nottingham Nottingham UK
PaeDiaTrics anD cHilD HealTH 184 196
infants Several self-report measures were used including the Brief Symptom Inventory the Parenting Stress Index (PSI) the Impact on Family Scale and the Family Inventory of Life Events and Changes (FILE) Mothers of VLBW infants had more psycho-logical distress at 1 month compared to mothers of term infants Mothers of high-risk VLBW infants also reported high psycho-logical distress at 2 years and high levels of parenting stress at 3 years Mothers have also been found to have higher stress levels compared to fathers Shaw et al3 examined the prevalence of acute stress disorder (ASD) in 40 parents whose infants were in the neonatal intensive care unit (NICU) Nearly half of the moth-ers (44) met the criteria for ASD although none of the fathers did Furthermore the severity of the symptoms (measured by the number of concurrent symptoms) was greater for the moth-ers than for the fathers3 The reasons behind this difference have been widely speculated with some believing that it is due to the mothersrsquo greater psychological involvement with the infant as evidenced by their general greater vulnerability to postpartum psychological disorder It could also reflect gender differences in coping style
Having an infant who requires intensive medical care repre-sents a significant emotional burden for families Not only is there extreme anxiety surrounding the infantrsquos health and distress for the childrsquos suffering there is also the unfamiliar and intimidating environment of the NICU to adjust to Hopper in her review of the literature identified sources of stress for parents of sick neo-nates as falling into three areas4 Situational factors included the severity of the infantrsquos illness and how parents adapted to the life crisis of having a sick infant Personal factors involved parental emotions about their roles and the instrumental and informa-tional support which were available to them The third area was classified as environmental sources of stress and included the environment of the NICU and the relationship between parents and members of staff This relationship has been examined by several studies in the nursing literature nurses are seen as ide-ally placed to provide the necessary support and information to parents with sick neonates However whilst some studies have shown that supportive and helpful hospital staff can have a posi-tive effect on parents other studies have highlighted the prob-lems and difficulties which can manifest It has been shown that parents and nurses often have very different ideas about issues eg the necessary skills and competencies needed in an NICU or the characteristics that make a lsquogood motherrsquo
Research has shown that there may be a relationship between high levels of parental stress and an increased likelihood of depression5 Postpartum depression is a psychiatric illness which appears in 10ndash15 of postpartum women Its reported preva-lence rates however have ranged from less than 10 up to 306 depending on the instruments used the population exam-ined and the timing of the research Several factors have been found to be associated with postpartum depression including poor social support and infant-related stressors6 Evidence indi-cates that postnatal depression may be underreported and this is of concern since the mental and psychological health of the mother can affect her relationship with her infant and thus the infantrsquos cognitive and emotional development5 Depressed moth-ers appear to look touch and talk to their infants less frequently and also appear to show fewer positive and more negative faces7 The vocalizations of mothers suffering with depression have also
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
been found to be less effective at promoting cognitive growth and learning in infants8
If researchers are interested in finding ways of providing sup-port for families of sick neonates then they must listen to what such families perceive their needs to be in order to avoid increas-ing anxiety and distress Furthermore the provision of appropri-ate support be it emotional informational or social will enhance parental coping abilities increase self-esteem and reduce anxiety It should be noted though that the research conducted around these issues has often taken lsquosupport needsrsquo as being synony-mous with lsquoinformation needsrsquo Such studies have examined the type the amount and quality of information that parents receive and perceive themselves as needing but have not explored in equal depth the perceived emotional support needs of families who have a sick infant In addition the needs of parents may change throughout their infantrsquos illness Ward examined the per-ceived needs of 52 parents of infants in an NICU9 Parents rated the needs of their hospitalized infant as most important along with the need to be reassured Interestingly they ranked their support needs as least important This research was conducted during the first week of the infantsrsquo hospitalization however which would explain the preoccupation of the parents with the infantrsquos health These results demonstrate that if researchers want to find ways of providing emotional support to parents of sick neonates they must be prepared not only to listen to parents but also to be flexible enough to satisfy the parentsrsquo changing needs and expectations
Interventions aimed at supporting parents
Most interventions that been evaluated in controlled studies have focused on supporting the motherndashinfant relationship and provid-ing information on infant development Many of these interven-tions have included the aim of improving the parental emotional state and thus psychological outcomes such as stress or anxi-ety have been assessed However few studies appear to include fathers This means that strategies implemented to provide emo-tional support to families of sick neonates are often derived from interventions tailored for mothers even though fathers may have different emotional needs
A wide range of interventions with mothers and infants has been evaluated in the NICU Increasing motherndashinfant contact through kangaroo care has been found to reduce maternal anxiety1011 and educational programmes delivered to fami-lies in the NICU have also been associated with reduced emo-tional difficulties in parents12ndash14 Kaaresen and colleagues implemented an intervention which consisted of eight sessions before discharge and four home visits all by trained nurses The sample included 71 premature infants in the intervention group 69 premature infants in the control group and 74 infants in the full-term control group The randomized controlled trial found that the intervention reduced parenting stress in both mothers and fathers of premature infants compared to controls to a level equivalent to parents in the term control group13 At 6 months corrected age mothers of preterm infants who had not received the intervention had total PSI scores which were 17 points higher than the mothers of infants born at term (an effect size of 057) A similar study evaluated the efficacy of an educationalndashbehavioural programmendashCreating Opportunities for
PaeDiaTrics anD cHilD HealTH 184 19
Parent Empowerment (COPE) ndash through a randomized controlled trial with 260 families of premature infants14 COPE was a four-phase educationalndashbehavioural programme which began as early as 2ndash4 d after mothers had given birth and continued until 1 week after discharge from the NICU The programme consisted of audiotaped and written infant behaviour information along with photographs which focused on common behaviours and characteristics of premature infants It also included various par-ent activities in the form of a four-phase workbook which aimed to assist mothers in the implementation of the experimental infor-mation COPE was found significantly to reduce maternal stress in the NICU as well as maternal anxiety and depressive symptoms after hospitalization In contrast a cluster randomized trial of a parenting intervention delivered to mothers of very premature infants from soon after birth showed no benefits for parenting stress1 The authors hypothesized that the intervention had not been of sufficient intensity particularly in the weeks surrounding discharge Neonatal care presents a significant barrier to parent-ing in the early weeks following a very preterm birth and so inter-ventions which focus on the developmental needs of infants and the parentndashchild relationship should particularly aim to support parents as they take on the parenting role There was also concern that the intervention had failed to reach those most at risk
Since large-scale projects can be costly to implement and may often fail to reach the families in most need it may be wiser to focus on intervention programmes which are more practical and easier to implement within a neonatal care setting Research has shown that even interventions which are based on one-off meet-ings with parents of sick neonates can be effective Jotzo and Poets examined the effect of an intervention programme aimed at reducing the severity of traumatic responses as a result of giv-ing birth prematurely15 Their programme consisted of a one-off intervention meeting along with additional psychological help throughout the hospitalization of the infant The meeting cov-ered a variety of issues including a reconstruction of the events shortly before and after the infantrsquos birth relaxation techniques discussion of coping strategies available resources and social support and support during emotional outbursts The measures used included the Impact of Event Scale (IES) and the Peritrau-matic Dissociative Experience Questionnaire At discharge the mothers who received the intervention were found to have a significantly lower traumatic impact as a result of premature birth Furthermore fewer mothers in the intervention group showed symptoms of clinically significant psychological trauma at discharge compared to mothers in the control group (36 vs 76)15 The lsquoParents Circle Programrsquo is another intervention with a similar structure16 This consisted of a 90 min session for parents with the aim of enhancing the developing relationship between parents and infants and to offer parents support A total of 104 parents (59 mothers and 45 fathers) and 44 members of hospital staff were asked to evaluate the programme and their results were analysed using content analysis Families reported gaining perspective on their situation feeling supported becom-ing aware of cues and optimizing interactions and becoming aware of available resources Parents and staff alike felt that participating in the intervention helped parents overcome the difficulties associated with the early time of their infantrsquos hos-pitalization Additional studies have also found positive results with fairly minimal interventions including discussion groups
7 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
in the NICU music during kangaroo care and pairing mothers of sick neonates with trained mothers who had been through similar experiences
Parent support programmes
Parent support programmes (PSPs) which are based in NICUs can provide parents with the opportunity to talk to parents who have been in similar situations and also to discuss their emo-tions with professionals who can help them cope with their situa-tion111718 The parent-to-parent support programme for mothers of preterm infants evaluated by Preyde and Ardal included edu-cational parental support group meetings and individual par-ent-to-parent support (primarily telephone support)19 Measures used included the Parental Stressor Scale NICU the State and the Trait Anxiety Inventories and the Beck Depression Inven-tory After 4 months of participation mothers in the intervention group reported lower levels of stress state anxiety and depres-sion compared to control group mothers The authors speculated however that the participants who were able to meet face to face with other parents were those who benefited the most Hurst conducted a comprehensive survey of an NICU-based PSP This PSP was provided in a variety of formats including a weekly parent support group hospital visitation and 24-h telephone sup-port20 Of the 477 participants 303 families used the PSP dur-ing a 2-year evaluation period with 78 using only one form of support and 18 using two forms Of a sub-sample of 48 parents asked to complete an evaluation of the PSP 92 stated that they would recommend such a programme to other parents Furthermore the majority of parents felt that it made them feel supported and helped them deal with their emotions20 This is an indication that such programmes can be very successful in sup-porting parents throughout their infantrsquos hospitalization It also shows that it can be beneficial to give parents several options and formats when it comes to such support services It is impor-tant to consider though that both the Hurst and the Preyde and Ardal studies found that some participants did not find the sup-port programmes helpful even reporting that they had caused them increased stress and anxiety Therefore it should not be assumed that support programmes will suit every individual and will provide the required support for all parents1920 NICUs need to be flexible enough to provide parents with a range of forms of support to choose from
The increased understanding of the strains that parents of sick neonates have to deal with has also led to efforts to improve customary practices in NICUs Family-centred care focuses on infants and their needs and attempts to redefine the relationship between parents and caregivers These practices strive to provide parents with support during their infantrsquos illness by focusing on freely sharing information and on the collaboration between parents and hospital staff Family-centred care has been found to be associated with several beneficial outcomes including improved parental satisfaction increased parental comfort staff satisfaction and decreased parental stress18 Research is already examining these practices and questioning how these can be improved further Such research reflects the increasing effort focused on lsquohumanizingrsquo the environment in NICUs in order to make parents feel more comfortable about spending time with their infants
PaeDiaTrics anD cHilD HealTH 184 19
Conclusion
Surprisingly few interventions have prioritized the provision of emotional support for parents of sick neonates or accounted for the changing needs and wishes of parents over the course of their infantrsquos care Large-scale supportive education-based inter-ventions have been shown to be effective in reducing parental distress However the feasibility and sustainability of such pro-grammes should also be considered Programmes which require significant additional resources can be expensive and there are also issues of training and quality control Interventions which require significant input from parents may also place additional burdens on families making them potentially less accessible to those most at risk Arguably the aim should be to explore ways of providing acceptable and effective informational support which could be complemented by emotional support from health professionals and from other parents in the unit Increasingly studies are exploring the use of computers and multimedia as an engaging flexible and cost-effective method of targeting indi-vidual needs and providing support and information Such com-puter-based and interactive multimedia interventions have been found to be successful with a range of patient groups and could therefore be examined as a complementary method of providing informational support to families with sick neonates
REfEREnCEs
1 Glazebrook c Marlow n israel c et al randomised trial of a
parenting intervention during neonatal intensive care Arch Dis Child
Fetal Neonatal Ed 2007 92 F438ndash443
2 singer lT salvator a Guo s collin M lilien l Baley J Maternal
psychological distress and parenting stress after the birth of a very
low-birth-weight infant JAMA 1999 281 799ndash805
3 shaw rJ Deblois T ikuta l Ginzburg K Fleisher B Koopman c
acute stress disorder among parents of infants in the neonatal
intensive care nursery Psychosomatics 2006 47 206ndash212
4 Hopper a sources of stress for parents of a sick neonate a
literature review Pediatr Nurs 2000 30 29ndash32
5 Davis l edwards H Mohay H wollin J The impact of very
premature birth on the psychological health of mothers Early Hum
Dev 2003 73 61ndash70
6 Bernazzani O saucier J-F David H Borgeat F Psychosocial
predictors of depressive symptomatology level in postpartum
women J Affect Disord 1997 46 39ndash49
7 Field T infants of depressed mothers Infant Behav Dev 1995 18
1ndash13
8 Kaplan Ps Bachorowski J-a Zarlengo-strouse P child-directed
speech produced by mothers with symptoms of depression fails
to promote associative learning in 4-month-old infants Child Dev
1999 70 560ndash570
9 ward K Perceived needs of parents of critically ill infants in
a neonatal intensive care unit (nicU) Pediatr Nurs 2001 27
281ndash286
10 lai Hl chen cJ Peng Tc et al randomized controlled trial of music
during kangaroo care on maternal state anxiety and preterm infantsrsquo
responses Int J Nurs Stud 2006 43 139ndash146
8 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
11 Tallandini Ma scalembra c Kangaroo mother care and mother-
premature infant dyadic interaction Infant Ment Health J 2006 27
251ndash275
12 Ohgi s Fukuda M akiyama T Gima H effect of an early intervention
programme on low birthweight infants with cerebral injuries
J Paediatr Child Health 2004 40 689ndash695
13 Kaaresen Pi ronning Ja Ulvund se Dahl lB a randomized
controlled trial of the effectiveness of an early-intervention program
in reducing parenting stress after preterm birth Pediatrics 2006
118 e9ndash19
14 Melnyk BM Feinstein nF alpert-Gillis l et al reducing premature
infantsrsquo length of stay and improving parentsrsquo mental health
outcomes with the creating opportunities for parent empowerment
(cOPe) neonatal intensive care unit program a randomized
controlled trial Pediatrics 2006 118 e1414ndash1427
15 Jotzo M Poets cF Helping parents cope with the trauma of
premature birth an evaluation of a trauma-preventive psychological
intervention Pediatrics 2005 115 915ndash919
16 Pearson J andersen K evaluation of a program to promote positive
parenting in the neonatal intensive care unit Neonatal Netw 2001
20 43ndash48
17 roman l lindsay J Boger r et al Parent-to-parent support
initiated in the neonatal intensive care unit Res Nurs Health 1995
18 385ndash394
18 Meyer ec coll cTG lester BM Boukydis cFZ McDonough sM Oh w
Family-based intervention improves maternal psychological well-
being and feeding interaction of preterm infants Pediatrics 1994
93 241ndash246
PaeDiaTrics anD cHilD HealTH 184 19
19 Preyde M ardal F effectiveness of a parent ldquobuddyrdquo program for
mothers of very preterm infants in a neonatal intensive care unit
CMAJ 2003 168 969ndash973
20 Hurst i One size does not fit all Parentsrsquo evaluations of a support
program in a newborn intensive care nursery J Perinat Neonatal
Nurs 2006 20 252ndash261
Practice points
bull Parents of sick neonates experience significant distress and
exhibit higher levels of stress anxiety and depression than
parents of healthy infants
bull educational support emotional support and increased
motherndashinfant contact have been shown to promote maternal
well-being
bull emotional support for fathers has been largely neglected in
the research literature
bull Parents benefit from a choice of supportive facilities which
could include face-to-face sessions with health professionals
telephone support hospital visitation parent-to-parent
support and unit-based group support meetings
bull Parentsrsquo support needs can change during their infantrsquos
hospitalization and not all parents want or benefit from the
provision of additional information and emotional support in
the neonatal unit
9 copy 2008 elsevier ltd all rights reserved
Personal Practice
When should enteral feeds be started in preterm infantsnicholas D embleton
AbstractPaediatricians are regularly faced with the question of when best to start
enteral feeds in preterm infants this is important as longer term out-
come may be compromised by sub-optimal nutrition in early life clinical
factors that may affect the decision to start and the risk and benefits
are discussed
Keywords breast milk feeding nutrition parenteral nutrition
Key points in the history
Alice is lsquonutritionally vulnerablersquo and whilst this may not be immediately apparent it will affect her long term outcome Her energy stores are extremely limited and consist primarily of pro-tein She has less than 5 fat and little energy associated with stored glycogen She is losing about 1 gkgd protein equivalent so she needs at least that and a minimum of 50ndash60 kcalkg of energy just to maintain the status quo let alone grow
Her weight is on the 25th centile Review of any antenatal his-tory may reveal whether fetal growth was normal Fetal growth retardation can occur with a weight greater than 10th centile The presence of antenatal absent or reversed end diastolic flow in the umbilical artery indicates poor gut blood flow This increases the risk of necrotizing enterocolitis (NEC) and might suggest a more cautious approach to starting feeds1
She has no important cardiovascular problems but if she were hypotensive gut blood flow may be low There is no umbilical
Nicholas D Embleton BSC (Hons) MBBS (Hons) MD FRCPCH is Consultant in
Neonatal Medicine at Newcastle Neonatal Service Royal Victoria
Infirmary Newcastle upon Tyne NE1 4LP UK
Should you start feeds at a day of age
alice was born following spontaneous labour at 30 weeksrsquo
gestation she weighed 1300 g and is now 18 h old she was
briefly ventilated and then extubated to continuous positive
airway pressure 12 h ago in 35 oxygen she has had caffeine
citrate but still has intermittent episodes of self-correcting
apnoea she was commenced on iv 10 dextrose but this was
replaced by a parenteral amino acid solution (referred to as
lsquotPnrsquo) along with intralipid at 0900 this morning serum glucose
is 11 mmoll and blood pressure is 42 systolic
PaeDiatrics anD cHilD HealtH 184 20
arterial catheter in situ but there is no good evidence that this should delay the decision to start feeds Her glucose is high but this is quite common in a baby like this Could this be a sign of sepsis Caffeine does not affect the incidence of NEC2 The great-est risk factor for NEC in this case is prematurity
What else might be found on examination
Up until 24 h ago she was swallowing large amounts of amniotic fluid What will have changed since then
General examination should confirm peripheral perfusion lsquogestaltrsquo view (does she look lsquowellrsquo) and cardiovascular status lsquoBowel soundsrsquo are not usually helpful
The most important variable likely to affect gut perfusion is the arterial duct Precordial lsquoheaversquo and a loud murmur are sug-gestive but it is possible to have a significant ductal shunt in a baby with a normal examination Cardiac ultrasound will con-firm this diagnosis It might be better to treat a large shunt first with indometacin and to delay starting feeds for a further 24 h
It is not possible to assess gut perfusion clinically but normal perfusion elsewhere (adequate urine output usually indicates adequate renal perfusion) would be reassuring Most preterm babies have a few abdominal lsquoloopsrsquo visible but a distended abdomen with many palpable loops suggests ileus This might be secondary to sepsis or poor gut blood flow Preterm babies do not pass much meconium in the first 24ndash48 h
Balance of risks between starting and withholding feeds
Alice requires 35ndash4 gkgd of protein and 120 kcalkgd to grow3 This will initially be provided parenterally Delaying feeds increases the risk of gut villous atrophy and prolongs the need for lsquototal parenteral nutrition (TPN)rsquo TPN requires intravenous access and so increases the risk of sepsis and when prolonged use is required combined with the lack of enteral feeding may result in hepatic impairment
Delaying feeds may allow a gut that has been chronically under-perfused to re-establish more normal perfusion although normal gut endocrine function digestive enzyme upregulation and motility require a source of intraluminal nutrients1 A recent study suggested benefit from delaying the introduction of feeds4 but methodologi-cal problems exist5 Although a Cochrane meta-analysis suggested no benefit only two studies were included6 A large UK-based trial is examining the effect of early or late feeding in preterm infants who were born growth retarded following identification of antena-tal absent or reversed end diastolic flow in the umbilical artery7
When starting feeds what volume should be used
There are no good data to guide this decision We start with 24 mlkg (1 mlkgh) and then increase by this amount each day Most babies achieve full enteral feeds (ge150 mlkgd) by a week of age Feeding guidelines improve the outcome8 Measure-ment or assessment of gastric aspirates is not consistently useful in predicting subsequent feeding intolerance or development of NEC Aspirate volumes equivalent to or sometimes greater than the amount given in the preceding 1ndash2 h are usually normal Most aspirates have a greenish colour Thick bloody or intensely bile-stained aspirates require detailed assessment
0 copy 2008 elsevier ltd all rights reserved
Personal Practice
What else affects decisions and outcome
Feeding success is affected by sepsis and NEC Scrupulous atten-tion should be paid to hand washing and intravenous access and blood sampling should be minimized There is no good evidence to support the routine use of pro-kinetic agents or H2 blockers
The most important clinical intervention affecting the occur-rence of NEC is the use of breast milk9 All efforts should be directed at persuading parents of the benefits and supporting the process Some clinicians delay starting feeds for a further 24 h whilst expressed breast milk becomes available Donor breast milk might be equally efficacious10
RefeRenceS
1 Dorling J Kempley s leaf a Feeding growth restricted preterm
infants with abnormal antenatal Doppler results Arch Dis Child Fetal
Neonatal Ed 2005 90 F359ndash363
2 schmidt B roberts rs Davis P et al caffeine therapy for apnea of
prematurity N Engl J Med 2006 354 2112ndash2121
PaeDiatrics anD cHilD HealtH 184 20
3 embleton nD Pang n cooke rJ Postnatal malnutrition and growth
retardation an inevitable consequence of current recommendations
in preterm infants Pediatrics 2001 107 270ndash273
4 Berseth cl Bisquera Ja Paje VU Prolonging small feeding volumes
early in life decreases the incidence of necrotizing enterocolitis in
very low birth weight infants Pediatrics 2003 111 529ndash534
5 Menon G Boyle eM embleton nD et al introduction of enteral
feeds in preterm infants Pediatrics 2004 114 327ndash328
6 Kennedy Ka tyson Je chamnanvanikij s early versus delayed
initiation of progressive enteral feedings for parenterally fed low
birth weight or preterm infants Cochrane Database Syst Rev 2000
cD001970
7 wwwnpeuoxacukadept
8 Patole sK de Klerk n impact of standardised feeding regimens on
incidence of neonatal necrotising enterocolitis a systematic review
and meta-analysis of observational studies Arch Dis Child Fetal
Neonatal Ed 2005 90 F147ndash151
9 lucas a cole tJ Breast milk and neonatal necrotising enterocolitis
Lancet 1990 336 1519ndash1523
10 Boyd ca Quigley Ma Brocklehurst P Donor breast milk versus
infant formula for preterm infants systematic review and meta-
analysis Arch Dis Child Fetal Neonatal Ed 2007 92 F169ndash175
1 copy 2008 elsevier ltd all rights reserved
self-assessment
Case 1A term male infant born to consanguineous parents is assessed at 24 h of age due to poor feeding profuse yellow watery diar-rhoea and irritability He weighed 32 kg at birth and delivery was uneventful There was no polyhydramnios He has been breastfed since birth On examination he is pale with a non-tender but distended abdomen and reduced bowel sounds His weight is 275 kg and he looks dehydrated Examination is otherwise normal
Initial investigations (normal values in parentheses) showed
sodium 149 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 65 mmollitre (25ndash75)
creatinine 147 μmollitre (40ndash110)
chloride 119 mmollitre (95ndash105)
haemoglobin 172 gdl (140ndash200)
White blood cell count 80 times 109litre (100ndash260)
Platelet count 302 times 109litre (150ndash400)
arterial blood gas
ph 720 (730ndash745)
PcO2 23 kPa (46ndash60)
Bicarbonate 68 mmollitre (220ndash260)
Base excess minus186 mmollitre (minus20 to +20)
lactate 59 mmollitre (06ndash24)
An abdominal X-ray shows distended bowel loops with no intramural thickening or pneumoperitoneum (Figure 1)
He was given nil by mouth and received intravenous fluids and antibiotics His dehydration improved but the metabolic acidosis and diarrhoea persisted despite receiving no enteral feeds and the commencement of total parenteral nutrition Blood and stool cultures were negative
1 Which of the following best describes these results Choose ONE answer ONLY from the followingA Hypernatraemia hyperchloraemic metabolic acidosis
with increased anion gapB Hypernatraemia hyperchloraemic metabolic acidosis
with normal anion gap
Manish Sadarangani BM BCh MA MRCPCH is Clinical Research Fellow
at the Department of Paediatrics University of Oxford Centre for
Clinical Vaccinology and Tropical Medicine Churchill Hospital
Oxford OX3 7LJ UK
Shabna Rajapaksa MB BChir MA MRCPCH is Specialist Registrar in
Paediatrics at the Paediatric Intensive Care Unit John Radcliffe
Hospital Oxford OX3 9DU UK
Nicholas Mann MD FRCP FRCPCH DCH is Consultant Paediatrician at the
Department of Paediatrics Royal Berkshire Hospital Reading RG1
5AN UK
self-assessment
C Hypernatraemic dehydration and compensated metabolic acidosis
D Acute renal failureE Renal tubular acidosis
2 What is the likely diagnosis Choose ONE answer ONLY from the followingA Hirschsprung disease ndash long segmentB Cystic fibrosis with meconium ileusC Microvillus inclusion diseaseD Cowrsquos milk protein intoleranceE Lactose intolerance
3 What is the investigation of choice Choose ONE answer ONLY from the followingA Rectal biopsy with staining for acetylcholine receptorsB Immunoreactive trypsinC Gastrointestinal endoscopy and biopsyD Stool microscopy and cultureE Stool reducing substances
Case 2A 4-year-old boy presents with a 3 d history of jaundice and a florid rash He has had orange urine and there is no change in his stool colour His family originate from Kosovo and have lived in the UK for the last 8 years He has never left the UK There is no history of blood transfusion or sex-ual abuse The grandmother was recently diagnosed with hepatitis B
On examination he is well apyrexial and mildly jaundiced with cervical and axillary lymphadenopathy He has an exten-sive papular rash over the face extremities and trunk (Figure 2) There is 3 cm hepatomegaly with no splenomegaly or ascites Examination is otherwise normal
Figure 1 abdominal X-ray of baby
Paediatrics and child health 184 202 copy 2008 elsevier ltd all rights reserved
self-assessment
Initial investigations are as follows
haemoglobin 110 gdl (113ndash135)
White blood cell count 108 times 109litre (50ndash150)
Platelet count 278 times 109litre (150ndash400)
inr 10 (08ndash12)
aPt ratio 10 (08ndash13)
sodium 140 mmollitre (135ndash145)
Potassium 42 mmollitre (35ndash50)
Urea 56 mmollitre (25ndash75)
creatinine 65 μmollitre (45ndash120)
total bilirubin 66 μmollitre (0ndash15)
conjugated bilirubin 23 μmollitre (0ndash10)
alanine aminotransferase (alt) 2033 iUlitre (0ndash35)
alkaline phosphatase 987 iUlitre (71ndash234)
Gamma-glutamyl transferase (GGt) 870 iUlitre (0ndash51)
1 What is the name of this rash Choose ONE answer ONLY from the followingA Erythema multiformeB Erythema migransC GianottiminusCrosti syndromeD EczemaE Dermatitis herpetiformis
2 What is the most likely diagnosis Choose ONE Answer ONLY from the followingA Autoimmune hepatitisB Hepatitis BC Hepatitis DD Wilson diseaseE Alpha-1 antitrypsin deficiency
3 What is the best means of management Choose ONE answer ONLY from the followingA Isolation until the jaundice disappearsB ImmunosuppressionC Copper chelating agents and genetic counsellingD Patient and family education with consideration of
antiviral agentsE Liver transplantation
Case 3A 10-month-old boy presents with 3 weeks of vomiting and constipation ndash he is passing hard stools every 2ndash3 days He has fallen from the 9th to below the 04th centile in the last 6 weeks He passed meconium within the first 24 h of life On examina-tion he looks pale and there are some dysmorphic features ndash a short nose long philtrum and wide mouth He has normal heart sounds with a grade 3 ejection systolic murmur loudest at the upper right sternal edge Examination is otherwise normal
Initial investigations are as follows
haemoglobin 91 gdl (113ndash141)
total white blood cell count 124 times 109litre (60ndash170)
Platelet count 407 times 109litre (150ndash400)
sodium 144 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 78 mmollitre (25ndash75)
creatinine 78 μmollitre (45ndash120)
albumin 52 glitre (35ndash50)
corrected calcium 384 mmollitre (238ndash263)
Phosphate 167 mmollitre (099ndash157)
1 What is the most likely diagnosis Choose ONE answer ONLY from the followingA HyperparathyroidismB Acute leukaemiaC Williams syndromeD Hypervitaminosis DE Familial hypocalciuric hypercalcaemia
2 Which investigation would be most useful in establishing the diagnosis Choose ONE answer ONLY from the followingA Intact parathyroid hormone assayB Blood filmC Fluorescent in-situ hybridization for 7q1123 deletionD 25-hydroxyvitamin D assayE Urine calciumcreatinine ratio
3 Which of the following treatments would not be suitable for this patient Choose ONE answer ONLY from the followingA Low calcium dietB Normal saline infusionC FurosemideD CorticosteroidsE Bisphosphonates
Case 4A 10-week-old girl presents with a 2-day history of poor feed-ing Her mother has been concerned about weakness since birth She only has a flicker of movement in the arms none in the legs and has a weak cry She has been passing urine and opening her bowels normally She was born at full term by normal delivery and did not require any resuscitation at birth Normal fetal movements were felt antenatally and there was no polyhydramnios She is the first child of non- consanguineous parents and there is no significant family his-tory On examination she is alert and fixing and following appropriately She has a weak cry and a weak suck There is reduced central and peripheral tone with marked head lag
Figure 2 rash found on examination
Paediatrics and child health 184 203 copy 2008 elsevier ltd all rights reserved
self-assessment
Muscle power is grade 3 out of 5 in the arms and legs There is no muscle or tongue fasciculation and she has absent reflexes throughout The remainder of the examination is normal
Electromyogram shows irregular polyphasic motor unit potentials with marked instability consistent with a dener-vating and re-innervating process (Figure 3)
1 Which of the following additional investigations may be helpful Choose ONE answer ONLY from the followingA Nerve conduction studiesB Creatine kinase assayC Muscle biopsyD SMN1 gene analysisE All of the above
2 What is the most likely cause of this childrsquos symptoms Choose ONE answer ONLY from the followingA Congenital myotonic dystrophyB Duchenne muscular dystrophyC PraderminusWilli syndromeD Spinal muscular atrophyE Mitochondrial myopathy
3 What is the mode of inheritance of this disease Choose ONE answer ONLY from the followingA X-linked recessiveB Autosomal recessiveC Autosomal dominantD MitochondrialE Sporadic
Case 5A 13-year-old girl presents with a 3-week history of fever up to 40degC night sweats and headache She has a reduced appetite with some weight loss She has no other specific symptoms She was on holiday in China 7 months ago On examination she looks well and has a temperature of 387degC There is no lymphadenopathy and no rashes Examination is entirely normal
Results of investigations are as follows
haemoglobin 126 gdl (120ndash160)
total white blood cell count 132 times 109litre (43ndash108)
neutrophil count 115 times 109litre (25ndash75)
Platelet count 244 times 109litre (150ndash400)
Blood film neutrophilia with left shift
erythrocyte sedimentation rate 63 mmh (1ndash20)
c-reactive protein 219 mglitre (0ndash5)
Blood culture Streptococcus intermedius
from anaerobic bottle only
csf culture negative
Magnetic resonance imaging (MRI) of the brain shows acute frontal sinusitis with a large intracranial frontal extra-dural empyema (Figure 4)
1 Which of the following would be appropriate management Choose ONE answer ONLY from the followingA A 12-week course of intravenous antibioticsB Drainage of the frontal sinus followed by 2 weeks of
intravenous antibioticsC Drainage of the empyema followed by 2 weeks of
intravenous antibioticsD Drainage of the empyema and the frontal sinus
followed by 2 weeks of oral antibiotics
1151
1152
1153
1154
1155
1156
1157
1158
1159
1200
50ms 1mV
Figure 3 electromyogram recording from the patient Figure 4 Parasagittal section from mri scan of patient
Paediatrics and child health 184 204 copy 2008 elsevier ltd all rights reserved
self-assessment
E Drainage of the empyema and the frontal sinus followed by 8 weeks of intravenous antibiotics
2 Streptococcus intermedius is a potential pathogen in which of the following infections Choose ONE answer ONLY from the followingA Liver abscessB Urinary tract infectionC MeningitisD Thoracic empyemaE Pneumonia
3 Which of the following statements regarding lsquopyrexia of unknown originrsquo in children is false Choose ONE answer ONLY from the followingA Malignancy is the underlying pathology in 5ndash15 of
casesB An aetiology will be found in over 90 of casesC The most common cause is infectionD A rheumatological cause is found in 10ndash20 of casesE Familial Mediterranean fever can occur in children of
non-Mediterranean ethnicity
Answers
Case 11 AThe anion gap is a useful tool to differentiate the causes of a metabolic acidosis It is calculated by the equation
Anion gap = [Na K ] [Cl HCO ]3+ + minus minus+ minus +
It represents the effect of unmeasured anions on the plasma pH and is normally 10ndash18 mmollitre
2 CMicrovillus inclusion disease is a severe autosomal recessive enteropathy that is typically apparent within hours or days after birth It is the second most common cause of protracted diarrhoea in the newborn after infectious causes It is characterized by severe yellow watery diarrhoea and malabsorption due to hypoplasia andor atrophy of the villi of the small intestine secondary to an inherited defect in the brush border membrane This results in severe dehydration malnutrition and metabolic acidosis due to bicarbonate loss from the gut
3 CDiagnosis of microvillus inclusion disease is made on small bowel biopsy Electron microscopy findings are of intracellular brush border inclusions and densely packed apical cytoplasmic vesicular bodies indicating microvillous atrophy There is no cure Treatment is supportive with total parenteral nutrition and consideration of small bowel transplantation
Further reAding
Goulet O ruemmele f causes and management of intestinal failure
in children Gastroenterology 2006 130(suppl 1) s16ndash28
rhoads Jm Vogler rc lacey sr et al microvillus inclusion disease
In vitro jejunal electrolyte transport Gastroenterology 1991
100 811ndash817
Case 21 CGianottindashCrosti syndrome is a distinct self-limiting rash commonly associated with viral infections in children between 2 and 6 years of age It presents as multiple pink to redminusbrown papules or papulovesicles which may be pruritic and can become confluent Gianotti and Crosti initially described the exanthema as associated with hepatitis B virus and they termed it papular acrodermatitis of childhood It can occur in several viral diseases eg hepatitis A B and C coxsackie viruses and cytomegalovirus
2 BHepatitis is a syndrome characterized by inflammation or injury of liver cells which may develop into cell necrosis and subsequently fibrosis andor cirrhosis Biochemically there are raised liver enzymes The degree of transaminase elevation does not correlate with the severity of the disease process Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of viral hepatitis
3 DHepatitis B infection is transmitted via blood sexually or vertically Infection may be acute or chronic Diagnostic markers are the presence of surface antigen (HBsAg) and HBV DNA The presence of e antigen (HBeAg) indicates high infectivity Infected newborns have a 95 risk of becoming carriers this risk decreases with infection acquired later in childhood Approximately 15ndash25 of HBV carriers will die from cirrhosis or hepatocellular carcinoma Extrahepatic findings are more common in older children and include membranous glomerulonephritis and GianottiminusCrosti syndrome Fulminant hepatic failure occurs in severe cases resulting in persistent jaundice encephalopathy and coagulopathy Management includes counselling family members monitoring for ongoing liver disease and consideration of antiviral therapy
Further reAding
Brandt O abeck d Gianotti r Burgdorf W Gianotti crosti
syndrome J Am Acad Dermatol 2006 54 136ndash145
slowik mK Jhaveri r hepatitis B and c viruses in infants and
young children Semin Pediatr Infect Dis 2005 16 296ndash305
Case 31 CHypercalcaemia is uncommon in infancy The most common symptoms in this age group are irritability vomiting and constipation It may be a manifestation of Williams syndrome vitamin D or calcium excess as well as disorders associated with reduced bone formation such as hypophosphatasia or increased bone resorption such as malignancy Occasionally
Paediatrics and child health 184 205 copy 2008 elsevier ltd all rights reserved
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-
SympoSium neonatology
requirements to maintain normoglycaemia) an operational thresh-old and therapeutic goal of 35 mmollitre has been proposed24
Finally there must be careful consideration of the infant of the diabetic mother In extreme and rare cases there may be signifi-cant but transient hyperinsulinism and in these cases the thera-peutic goal must be 35 mmollitre More commonly babies whose mothersrsquo diabetes has been well controlled will have normal lsquotran-sitional hypoglycaemiarsquo or slightly delayed metabolic adaptation while insulin levels fall postnatally There must be careful and repeated clinical assessment including blood glucose monitoring For infants of diabetic mothers who have no evidence of signifi-cant hyperinsulinism and no abnormal clinical signs there is no evidence that the operational threshold for hyperinsulinism must be applied Indeed to do so would result in separation of large numbers of healthy babies from their mothers with the conse-quent impact upon breast feeding and resource allocation25
The operational thresholds for various groups of babies are summarized in Table 2
The guidance relating to operational thresholds is predicated upon the accurate measurement of blood glucose levels It is now well known that the commonly used reagent strips are insufficiently accurate to diagnose hypoglycaemia and monitor at-risk infants and there must be access to equipment which allows immediate and accurate determination of blood glucose levels1426ndash28
Blood glucose monitoring
An accurate method for blood glucose monitoring must be employed as described above The sample should be free flowing venous or from a warm heel such that the blood flows freely without squeezing
Blood of high haematocrit often yields low blood glucose lev-els because of dilution of glucose by red cell water However this is also clinically relevant because polycythaemia is itself a high-risk situation Therefore in polycythaemic infants both the haematocrit and blood glucose level must be monitored and both acted upon accordingly
Operational thresholds for blood glucose levels in the management of babies at risk of impaired metabolic adaptation124
Clinical condition Blood glucose level at which
to consider intervention and
therapeutic goal
all at-risk babies lt10 mmollitre
abnormal neurological
signs
intervene regardless of blood
glucose levelSystematically unwell baby therapeutic goal of 25 mmollitre
at-risk babies no abnormal
neurological signs
persistently lt20 mmollitre
Hyperinsulinism 35 mmollitre
Table 2
paeDiatRiCS anD CHilD HealtH 184 163
Only babies in at-risk groups or babies who have abnormal neurological signs should be subjected to blood glucose monitor-ing (Table 3)
It is important not to commence blood glucose monitoring too soon after birth as to do so would fail to differentiate the baby with incipient hypoglycaemia from the baby undergoing the nor-mal postnatal fall in blood glucose level It is recommended in the otherwise healthy but at-risk baby to wait until around 3 h after birth to make the first blood glucose estimation2528 In prac-tice this is usually before the second feed assuming best practice of offering a baby a breast (or if necessary formula feed) imme-diately after birth Clearly if the baby is unwell or has abnormal clinical signs in the first 3 h they will be treated according to clinical condition which will include intravenous fluids and the therapeutic goal described above would apply
Similarly the temptation to measure blood glucose level shortly (within 2 h) after intravenous glucose has been discon-tinued must be avoided In this circumstance as at birth blood glucose levels fall and then subsequently rise in response to coun-ter-regulation It is this effective rise which must be assessed by blood glucose measurement at least 2 h after a change is made (provided the baby remains clinically well)
Blood glucose levels rise after a feed and fall to a nadir before the subsequent feed As our concern is the lowest blood glucose level during the feed cycle and as this measurement may assist in determining best feed frequency it is important that pre-feed blood glucose concentration is measured There is no clinical value in measuring a post-feed blood glucose level as this may be falsely reassuring and this practice subjects babies to more frequent heel pricks or venesections than is necessary
Finally consideration must be given to when to discontinue blood glucose monitoring This will depend upon the babyrsquos clin-ical condition feeding pattern and underlying disorder or risk factors for impaired metabolic adaptation
Prevention and management of clinically significant hypoglycaemia
In babies at risk of clinically significant hypoglycaemia and who are well enough to tolerate enteral feeds milk feeds are the
At-risk babies for whom blood glucose monitoring is recommended
abnormal neurological signs
Systemically unwell eg suspected or proven infection
hypoxicndashischaemic encephalopathy
preterm (lt 37 weeks)
intrauterine growth restriction (lt 2nd centile and any baby with
signs of wasting)
infant of diabetic mother
polycythaemia
maternal beta-blocker medication
Suspected hyperinsulinism
Suspected inborn error of metabolism or endocrine disorder
Table 3
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
mainstay of prevention For babies who are able to feed orally breast feeding should be first choice and there must be maximal support for the mother to do so This is a key clinical priority for midwives and paediatricians
If there are concerns regarding adequacy of breast feeding to prevent hypoglycaemia the mother should be encouraged to commence expression of milk from very soon after birth If there is insufficient breast milk to prevent babies reaching the opera-tional thresholds described above there should be judicious use of formula milk using only the smallest amount required to keep the babyrsquos glucose in the required range Formula milk in exces-sive quantities has been demonstrated to suppress normal meta-bolic adaptation2122
In babies for whom early enteral feeds are not appropriate or not tolerated or for whom enteral feeding does not prevent blood glucose level falling below operational thresholds intravenous glucose infusion at rates around 4ndash5 mgkgmin (58ndash72 mlkgd of 10 dextrose) are usually sufficient to prevent hypoglycae-mia If blood glucose levels remain below therapeutic goals the rate of infusion may be steadily increased Excess glucose infu-sion over and above that required to maintain the therapeutic goal will stimulate insulin and there is a risk of rebound hypo-glycaemia if high rate glucose infusions are too rapidly reduced Milk feeds if tolerated should be continued if intravenous glu-cose is commenced
If infused volume of glucose solution becomes excessive in order to maintain therapeutic goals or if fluid restriction must be applied more concentrated glucose concentrations must be infused through a central venous line This is particularly rel-evant to the hyperinsulinaemic baby in whom glucose infusion rates in excess of 8ndash10 mgkgmin are required to maintain ther-apeutic goals There is a high risk of severe and brain-damaging hypoglycaemia if treatment is delayed or fails to raise blood glu-cose levels and management of these babies requires consulta-tion with or referral to a specialist centre24
If there is presentation of hypoglycaemia with abnormal clinical signs or a very low blood glucose level (less than 1 mmollitre) this mandates urgent treatment with intravenous glucose The rates of glucose infusion described above are usually sufficient to bring the blood glucose level rapidly to the therapeutic goal without a bolus of glucose being necessary In fact a bolus dose of glucose will result in a peak blood glucose level and then an insulin surge making subsequent management problematical This is minimized by the use of a lsquomini-bolusrsquo should a bolus of glucose be required ndash 200 mg glucosekg (2 mlkg of 10 dextrose)28 Indications for mini-bolus are infants presenting with fits or coma or an lsquounre-cordablersquo or zero blood glucose level A mini-bolus should always be followed with glucose infusion or an increased glucose infusion rate if a baby already receiving intravenous glucose has required a mini-bolus
The temptation to supplement enteral feeds with glucose polymers and energy supplements (eg Duocal) or to use oral glucose gels or solutions (eg Hypostop) should be avoided as this carries a risk of necrotizing enterocolitis is likely to suppress normal metabolic adaptation and will suppress the appetite of the baby for effective oral feeding
Finally there are additional medications which may be employed in specific circumstances (Table 4) More detailed descriptions are given elsewhere242728 Babies who have hypoglycaemia which
paeDiatRiCS anD CHilD HealtH 184 164
is difficult to control by the measures described above and who require these additional treatments should be cared for in a centre which has expertise in metabolic and endocrinological conditions
Summary
Much controversy and confusion has surrounded neonatal hypo-glycaemia but this usually arises as a result of failure to under-stand the processes of normal metabolic adaptation and the fact that hypoglycaemia is a presenting sign rather than a diagnosis in itself Plans for investigation and management must be based upon the most likely underlying cause of impaired metabolic adaptation and take into account the clinical condition of the baby This is counter to the current trend to propose rigid pro-tocols and algorithms and re-introduces the value of detailed clinical evaluation and decision making The mainstay of man-agement is close clinical observation of vulnerable infants and energy provision tailored to their individual needs whilst avoid-ing excessively invasive management (namely unnecessary sep-aration of mother and baby routine or excessive formula milk supplementation or intravenous glucose administration) which themselves inhibit protective metabolic responses and impede successful establishment of breast feeding
ReFeRenCeS
1 Cornblath m Hawdon Jm Williams aF et al Controversies regarding
definition of neonatal hypoglycemia Suggested operational
thresholds Pediatrics 2000 105 1141ndash1145
2 Cornblath m ichord R Hypoglycemia in the neonate Semin
Perinatol 2000 24 136ndash149
3 Vannucci RC Vannucci SJ Hypoglycaemic brain injury Semin
Neonatol 2001 6 147ndash155
4 Rozance pJ Hay WW Hypoglycaemia in newborn infants features
associated with adverse outcomes Biol Neonate 2006 90 74ndash86
5 Hawdon Jm Hypoglycaemia in newborn infants defining the
features associated with adverse outcomes ndash a challenging remit
Biol Neonate 2006 90 87ndash88
6 Williams aF neonatal hypoglycaemia clinical and legal aspects
Semin Fetal Neonatal Med 2005 10 363ndash368
7 Soothill pW nicolaides KH Campbell S prenatal asphyxia
hyperlacticaemia hypoglycaemia and erythroblastosis in growth
retarded fetuses BMJ 1987 294 1051ndash1053
Additional medication in specific conditions (if these are required there must also be referral to a specialist centre)
Medication Indication
glucagon intramuscular bolus dose of 200 μgkg
transient rise in blood glucose level eg
when difficulty re-siting intravenous infusion
Diazoxide Hyperinsulinism
Hydorcortisone pituitary or adrenal insufficiency
Table 4
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
8 Hawdon Jm Ward platt mp mcphail S Cameron H Walkinshaw Sa
prediction of impaired metabolic adaptation by antenatal Doppler
studies in small for gestational age fetuses Arch Dis Child 1992
67 787ndash792
9 Deshpande S Hawdon Jm et al adaptation to extrauterine life in
Rodeck C Whittle m eds Fetal medicine Basic Science and Clinical
practice edinburgh Churchill livingstone 1999
10 Ward platt m Deshpande S metabolic adaptation at birth Semin
Fetal Neonatal Med 2005 10 341ndash350
11 eyre Ja Stuart ag Forsyth RJ Heaviside D Bartlett K glucose
export from the brain in man evidence for a role for astrocytic
glycogen as a reservoir of glucose for neural metabolism Brain Res
1994 28 349ndash352
12 Hawdon Jm Ward platt mp aynsley-green a patterns of metabolic
adaptation for preterm and term infants in the first neonatal week
Arch Dis Child 1992 67 357ndash365
13 Hawdon Jm Ward platt mp aynsley-green a prevention and
management of neonatal hypoglycaemia Arch Dis Child Fetal
Neonatal Ed 1994 70 F60ndash64
14 Hawdon Jm Hypoglycaemia and the neonatal brain Eur J Paediatr
1999 158 S9ndash12
15 massieu l Haces ml montiel t Hernaacutendez-Fonseca K acetoacetate
protects hippocampal neurons against glutamate-mediated neuronal
damage during glycolysis inhibition Neuroscience 2003 120
365ndash378
16 yamada Ka Rensing n thio ll Ketogenic diet reduces
hypoglycaemia-induced neuronal death in young rats Neurosci Lett
2005 385 210ndash214
17 nehlig a Brain uptake and metabolism of ketone bodies in animal
models Prostaglandins Leukot Essent Fatty Acids 2004 70
265ndash275
18 Hernaacutendez mJ Vannucci RC Salcedo a Brennan RW Cerebral blood
flow and metabolism during hypoglycemia in newborn dogs
J Neurochem 1980 35 622ndash628
19 Vannucci RC nardis ee Vannucci SJ Campbell pa Cerebral
carbohydrate and energy metabolism during hypoglycaemia in
newborn dogs Am J Physiol 1981 256 H1659ndashH1666
20 anwar m Vannucci RC autoradiographic determination of regional
cerebral blood flow during hypoglycaemia in newborn dogs Pediatr
Res 1988 24 41ndash45
21 Hawdon Jm Williams aF et al Formula supplements given to
healthy breastfed preterm babies inhibit postnatal metabolic
adaptation results of a randomised controlled trial Arch Dis Child
2000 82 a30
paeDiatRiCS anD CHilD HealtH 184 16
22 de Rooy l Hawdon Jm nutritional factors that affect the postnatal
metabolic adaptation of full-term small- and large-for gestational
age infants Pediatrics 2002 109 e42
23 Hawdon Jm Hypoglycaemia and brain injury ndash when neonatal
metabolic adaptation fails in levene m ed Fetal and neonatal
neurology and neurosurgery edinburgh Churchill livingstone in
press
24 Hussain K Congenital hyperinsulinism Semin Fetal Neonatal Med
2005 10 369ndash376
25 acolet D Diabetes in pregnancy Caring for the Baby after Birth
CemaCH 2007 2
26 Hussain K Sharief n the inaccuracy of venous and capillary blood
glucose measurement using reagent strips in the newborn period
and the effect of haematocrit Early Hum Dev 2000 57 111ndash121
27 Hawdon Jm Disorders of blood glucose homeostasis in the neonate
in Rennie Jm ed Robertonrsquos textbook of neonatology 4th edn
edinburgh Churchill livingstone 2005
28 Deshpande S Ward platt mp the investigation and management
of neonatal hypoglycaemia Semin Fetal Neonatal Med 2005 10
351ndash361
Practice points
bull identify risk factors for impaired metabolic adaptation
bull Clinical monitoring including accurate blood glucose
measurement for at-risk babies
bull Feed at-risk babies soon after birth and maintain thermal
homeostasis
bull take first blood glucose level at 3ndash4 h of age
bull intervene in at-risk baby with no clinical signs if two
consecutive blood glucose measurements lt 20 mmollitre
bull intervene in any baby with blood glucose measurement
lt 10 mmollitre
bull intervene in any baby with abnormal clinical signs regardless
of blood glucose level
bull investigate for underlying cause of failure of metabolic
adaptation
bull maintain lactation and breast feeding
5 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Resuscitation of the term and premature babyJonathan Wyllie
Abstractalthough most newly born babies establish normal respiration and
circulation without help up to 1minus2 may require some resuscitation
or stabilization Babies who do not establish adequate regular normal
breathing or who have a heart rate of less than 100 beatsmin or other
problems such as prematurity may require assistance the differences in
approach to the resuscitation of such babies originate in the physiology
and pathophysiology of acute asphyxia at birth However management
of airway and breathing remain the key features of resuscitation and
where cardiac depression has occurred this is nearly always due to hy-
poxia secondary to respiratory compromise therefore most babies will
respond within 2minus3 min of effective aeration of the lungs and the need
for intubation chest compressions or drugs is rare the international
liaison Committee on Resuscitation (ilCoR) evaluated evidence in 2000
and 2005 in order to provide guidelines for resuscitation they will do
so again for 2010 this evidence is limited in terms of both quantity and
quality and controversies still exist more research is needed to ensure
that our future actions are based upon evidence rather than history this
article will review the recommended approach to resuscitation as well as
some newer evidence
Keywords guidelines neonatal newborn premature resuscitation
Background
In the UK 669 601 babies were born alive in 2006 and most made the transition to extrauterine life without problems Those babies who did not establish adequate regular normal breathing or who had a heart rate of less than 100 beatsmin may have required assistance1 Factual evidence concerning the true requirement for resuscitation at birth is sparse Up to 10 of newborns may require some assistance to begin breathing with less than 1 needing extensive resuscitation2 However just because a baby received resuscitation does not necessarily mean that it was required and rates of intervention may be altered by educa-tion34 or the personnel present at deliveries5 In a UK tertiary centre with a standard approach to resuscitation at birth up to 12 of all babies received some airway assistance with just over 1 being intubated3 In Sweden only 1 of babies over 2500 g required mask or endotracheal tube ventilation at birth of which most responded to the former4
Jonathan Wyllie MBChB FRCPCH is Consultant Neonatologist at the James
Cook University Hospital Marton Road Middlesbrough TS4 3BW UK
paeDiatRiCS anD CHilD HealtH 184 16
Sometimes it is possible to predict babies who are likely to have respiratory depression at birth and to have appropriate per-sonnel present at delivery Guidelines for attendance at deliveries will vary with institution but even when almost 40 of deliv-eries are attended there may still be a further 15 of babies who require unexpected resuscitation5 a proportion that seems to remain whatever changes are made
The physiology of babies requiring help at birth has been summarized previously167 It allows a logical approach to resus-citation (Figure 1) when evidence is lacking and may prompt further research
Resuscitation at birth
PreparationAt birth resuscitation is more likely in babies with intrapartum evidence of significant fetal compromise those less than 35 weeksrsquo gestation those delivering vaginally by the breech and in multiple births Personnel trained in newborn resuscitation should be available at every delivery1 Someone experienced in tracheal intubation and advanced resuscitation should also be easily available for normal low-risk deliveries in hospital and ideally in attendance for deliveries with an increased likelihood of needing resuscitation In the latter cases the equipment and environment can be prepared beforehand including a discussion with the parents Wash your hands put on gloves and consider what help may be needed
Cord clampingAt birth it has long been known that delay in clamping the cord will lead to less anaemia in babies and reduce subsequent iron deficiency8 However few hospitals have practised this interven-tion due to worries about hypothermia and the need to resusci-tate or stabilize babies In developed countries the advantages seemed to be outweighed by the potential disadvantages A recent randomized controlled study of delayed clamping of the cord in premature babies found that the intervention group had less late-onset sepsis and fewer intraventricular haemorrhages9 This is a low-risk strategy which needs further evaluation in order to introduce it without increasing other risk factors in pre-mature deliveries
Assessment and temperature controlAssessment and temperature control for the newborn baby should occur at all deliveries The assessment indicates the need for resuscitation Babies may vary from 23 to 40+ weeksrsquo ges-tation and in weight from 500 to 5000 g They are born naked and wet and if left cannot cope with an environmental tem-perature of less than 32degC However if the term baby is imme-diately dried put skin-to-skin with the mother and covered the delivery room temperature can be as low as 25ndash28degC Obviously the smaller the baby the greater the surface area to mass ratio and the greater the risk of hypothermia Compromised babies are particularly vulnerable10 and hypothermia will lower oxygen tension11 increase metabolic acidosis12 and inhibit surfactant production13
An effective method of maintaining the temperature of prema-ture babies less than 28 weeksrsquo gestation is wrapping them with plastic before drying and then placing them under a radiant
6 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Dry the babyRemove any wet towels and cover
Start the clock or note the time
Give 5 inflation breathsLook for a response
If no increase in heart rate look for chest movement
Re-check head positionApply Jaw thrust
Repeat inflation breathsLook for a response
If no increase in heart rate look for chest movement
Try alternative airway opening manoeuvresRepeat inflation breaths
Look for a response
If no increase in heart rate look for chest movement
If the heart rate is not detectable or slow (lt60)Start compressions
3 compressions to each breath
Reassess heart rate every 30 secondsConsider venous access and drugs
Assess colour tone breathing and heart rate
Open the airway
If not breathing
If still not breathing
If no response
If still no response
When the chest is moving
If meconium present
Baby breathing wellDo not suction the airway
Baby floppy and not breathing wellConsider inspection and suction before
inflation breaths
Head in neutral position
Inflation breathsUse a well-fitting face mask
connedted to a
pressure-limited gas supply
Each breath 2ndash3 seconds
duration at 30 cm H2O for a
term baby
Get help from a second personto support the airway andor
inspect the oropharynx under
direct vision and consider
suction andor insert an
oropharyngeal airway
Chest compressionsCompvent ratio 31
Rate 120 events per minute
Ensure the chest moves with each ventilation breath
If breathingReassess heart rate and monitor baby
If heart rate is satisfactory but increasingContinue ventilation breaths at about 30 per
minute until baby is breathing adequately
If heart rate is satisfactory but increasingContinue ventilation breaths at about 30 per
minute until baby is breathing adequately
If heart rate is increasingStop compressions
Continue ventilation breaths at about 30 per
minute until baby is breathing adequately
If the chest is not movingRecheck head position and repeat inflation
breaths If competent consider intubation
If the chest is still not movingThe airway is the problem
Figure 1 newborn life support (Courtesy of the Resuscitation Council uK)
heater14 There is a small risk of hyperthermia so the temperature must be monitored carefully
An assessment is made of the babyrsquos colour tone respira-tions and heart rate127 The most important of these is heart rate and a stethoscope is more reliable than cord pulsation15 How-ever saturation monitors may offer a more reliable assessment of both heart rate and colour16 but their interpretation requires a detailed knowledge of normal saturations at birth at differing gestations A baby who is apnoeic and floppy in the absence of neurological disease is unconscious and likely to be in terminal apnoea however this does not change the initial approach other
paeDiatRiCS anD CHilD HealtH 184 167
than the need to summon help early APGAR scores are never calculated to guide resuscitation
Airway
If a baby is in primary apnoea then with an open airway the first gasp will start to aerate the lungs and most babies will be able to lsquoresuscitatersquo themselves as shown in physiological stud-ies on animals Neutral positioning of the babyrsquos head chin lift jaw thrust oropharyngeal airways and endotracheal intubation may all be helpful in certain situations if performed correctly17
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Endotracheal intubationThe placement of an endotracheal tube has long been the gold standard of airway control and this remains true in the unconscious baby if it is correctly sized placed and fixed in a timely manner However experience is directly related to effec-tiveness in endotracheal intubation1819 and the success rate of less experienced clinicians such as a resident (STA1-3) or a fel-low (STA3-5) is lower varying between 33 and 68 Even senior neonatologists often take longer than guidelines recom-mend19 Experienced clinicians may judge correct endotracheal position visually or by an increase in heart rate with the first breaths but detection of exhaled carbon dioxide will give more rapid confirmation in larger babies12171920 and this can be par-ticularly useful for less experienced clinicians or those supervis-ing them However not all systems for the detection of exhaled carbon dioxide work in the smallest premature infants
Laryngeal masksLaryngeal masks may be effective for ventilating term newborn babies but there are few data for small premature infants There have been reports of dislodged laryngeal airways during paedi-atric arrests when chest compressions have been administered Although success of placement at first attempt by paediatri-cians is greater with a laryngeal mask than with an endotra-cheal tube21 the only and small randomized controlled trial in the delivery room favoured endotracheal intubation when per-formed by an anaesthetist22 Based mainly upon case reports the laryngeal mask can be recommended when positioning and mask ventilation and endotracheal intubation have failed to secure the airway but not as yet as a primary method of airway control
MeconiumIn 2000 Wisewell et al23 reported a large randomized controlled trial showing that tracheal intubation and suctioning of meco-nium-stained but vigorous babies at birth did not reduce the incidence or severity of meconium aspiration syndrome More recently another randomized trial has now shown that suction-ing on the perineum similarly offers no benefit24 Neither of these practices is recommended but intubation and suction of meconium from the trachea of non-vigorous babies born through meconium-stained liquor is still recommended
Breathing
In the apnoeic baby the first breaths establish the resting lung volume and aerate the fluid-filled alveoli This mechanical effect aided by surface tension within the alveoli causes the initial fall in pulmonary vascular resistance Experimentally this effect occurs even if the lungs are ventilated with nitrogen but is increased when air is used presumably due to the vasodilator effect of 21 oxygen The mechanical stretching of the lung also triggers the activation of cyclo-oxygenase beginning the production of prostacyclin Bradykinin is produced which has a further direct vasodilator effect and also possibly via prostacyclin Therefore adequate airway control and passive ventilation is vital not only because babies requiring resuscitation at birth have an almost uniformly respiratory aetiology but also in order to promote post-natal adaptation and reverse any maladaptation
paeDiatRiCS anD CHilD HealtH 184 16
In term babies peak ventilatory pressures of 20ndash30 cmH2O may be required but the minimal pressure needed to achieve an improvement in heart rate should be used or if there is no response chest wall movement Longer breaths at lower pressure may be more effective in displacing alveolar fluid and establish-ing the resting lung volume in lungs with sufficient surfactant and may improve initial oxygenation However premature new-borns are obviously physiologically and anatomically less pre-pared for delivery than infants at term Over-inflation has been implicated in histological lung damage in animal models and high tidal volumes appear to be equally damaging whether given before or immediately after administration of surfactant How-ever the same effect is not seen if these excessive tidal volumes are delivered 15 min after administration of surfactant2526 It is now thought that both excess end expiratory volume and inad-equate end-expiratory volume may cause lung damage2728 In premature infants it would therefore seem sensible to use lower pressures of 20ndash25 cmH2O12 delivered in a controlled way to prevent over-inflation and to apply positive end-expiratory pres-sure (PEEP) to prevent damage from under-inflation PEEP also improves both lung compliance and gas exchange2930 Without PEEP the airways collapse during the expiratory phase in animal models of newborn resuscitation
If animal data can be extrapolated it would also seem appro-priate to give surfactant as soon as possible to premature babies in order to ameliorate damage2526
The majority of newborn infants requiring resuscitation will re-establish regular respiration after administration of a few breaths which may be due to Headrsquos paradoxical reflex by which the inflation triggers an inspiratory effort
VentilationOnce the lungs are aerated if the newborn remains apnoeic ventilation should be continued at 30ndash60 breathsmin avoiding hyperventilation and using the minimum pressure possible to maintain a heart rate greater than 100 beatsmin
Face mask the majority of infants who require ventilation receive it via a face mask This may be attached to a bagvalve system with a spring lsquoblow offrsquo system or a lsquoT-piecersquo with a set flow and pressure It is important to realize that the bagvalve system is flow sensitive and that the harder the operator presses the greater the flow and the higher the delivered pressure In fact 60 cmH2O can be achieved with vigorous squeezing of a self-inflating bag Therefore it may be advantageous that most opera-tors are unlikely to be as effective as they suppose in creating a seal with the mask31 This is a skill that requires tuition and prac-tice31 In delivering a set pressure T-piece systems such as the Tom Thumbcopy or Neopuffcopy perform better than any bagminusvalve system but require a gas supply There is no evidence that lung compliance can be assessed using any bag system
Continuous airway pressure case series have suggested that early or delivery room use of continuous positive airway pres-sure (CPAP) in premature babies may reduce chronic lung dis-ease There have been two randomized trials of which one was a pilot study The data from the COIN trial do not show any advan-tage other than a reduction in intubation and surfactant use in the intervention group However an excess of pneumothorax
8 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
was also reported The Vermont Oxford Network and the SUP-PORT trials will provide further data but at present the delivery room use of CPAP cannot be widely recommended and should be limited to those units experienced in its use or taking part in research
Air or oxygen oxygen has been in widespread use for resuscita-tion at birth since the 1930s and even hyperbaric oxygen was seriously supported in the 1960s For many years there have been concerns about tissue damage from oxygen deprivation during and after resuscitation It became evident in the 1950s that unrestricted oxygen therapy could have serious conse-quences for future vision More recently concerns have been raised about potential adverse effects on respiratory physiology cerebral circulation and tissue damage from oxygen free radicals even during resuscitation A meta-analysis of four human studies demonstrated a reduction in mortality and no evidence of harm in infants resuscitated in air versus 100 oxygen3233 However there are several significant methodological concerns with these studies and the results should be interpreted with caution There is insufficient evidence to recommend any specific concentration of oxygen to be used for newborn resuscitation Monitoring the oxygen saturation of babies may be helpful but as yet there are no time-related normal target ranges and healthy term babies may take up to 10 min to achieve preductal oxygen saturation of greater than 95 and up to 60 min to achieve this postductally
There is therefore equipoise which would be open to an appropriate randomized controlled trial In the meantime the evidence only supports use of either 21 or 100 oxygen It is provoking to realize that if air had been in constant use since the 1930s there would be insufficient evidence for use of supple-mental oxygen
Circulation
Early resuscitation (temperature control airway breathing) provides oxygenated blood in the pulmonary arterioles which if returned to the heart causes the rate to increase34 If due to acidosis and hypoxia the circulation is ineffective then chest compressions may be needed They should be commenced when the heart rate remains below 60min despite effective airway and breathing management127 The best technique is using two hands to encircle the chest1 A ratio of three compressions to one breath is internationally accepted127 but has no evidence to support it Research has shown that neither compressions nor drugs will work in this situation without oxygenated blood so effective lung aeration and ventilation is essential A logical approach would be to fill the alveoli with air and to compress the chest until they are empty However training and teamwork require an agreed ratio which has therefore not changed since guidelines were first agreed internationally Success is assessed by an increase in heart rate which should therefore be assessed every 30 s Compressions stop when the spontaneous heart rate is greater than 60 beatsmin
In hypoxic newborn animal models successful resuscitation can restore cardiac output and blood pressure to levels above baseline within 5ndash10 min However it should be noted that there is a decline to 30 lower than basal levels within 2 h and that blood pressure is relatively spared suggesting an even greater
paeDiatRiCS anD CHilD HealtH 184 16
reduction in tissue perfusion This should be considered in the later care of any neonate who was hypoxic at birth
Drugs
Neonatal bradycardia at birth is almost always due to hypoxia plusmn acidosis and therefore drugs are rarely needed Adrenaline (epi-nephrine) is reported as being used in between 1 and 4 babies per 2000 births which is a large variation in practice Reported success is also variable and must be interpreted in light of this variation The use of drugs in extremely premature infants is con-troversial Some data suggested good outcomes for babies below 28 weeksrsquo gestation given adrenaline but these were flawed by high numbers of babies receiving resuscitative drugs some before the airway had been appropriately managed Audit data now suggest a poor outcome such that many clinicians would now council against the use of adrenaline and other drugs to resuscitate extremely premature newborn babies
Adrenaline (epinephrine)In 2003 a Cochrane review of randomized controlled trials involv-ing adrenaline use for resuscitation of neonates was unable to identify a single clinical trial35 Despite the lack of human neo-natal data animal models show the potential of adrenaline in asphyxial cardiac arrest and it is reasonable to use it when ade-quate ventilation and chest compressions have failed to increase the heart rate above 60 beatsmin Use 10ndash30 μgkg intrave-nously and preferably via an umbilical venous line The tracheal route cannot be recommended but if used it is likely that doses within this range will be ineffective and 100 μgkg might be tried However the safety of such doses has not been studied
BicarbonateThe use of bicarbonate has long been controversial but many of the concerns relate to the rapid correction of acidosis in neonates after resuscitation or the routine use of bicarbonate infusion nei-ther of which can be advocated There are no published human neonatal data to support its use although some exist from animal studies Animal data have also shown that the binding of adren-aline to receptors in the myocardium is significantly impaired by lactic acidosis and recent work on human lymphocyte beta-adrenergic receptors supports this view Whether this is also true of the more important alpha receptors is unknown In practice reversing intracardiac acidosis may improve myocardial function and assist in achieving a return of spontaneous circulation 1ndash2 mmolkg of bicarbonate may be given but this remains a contro-versial area
VolumeVolume expansion should only be given when it is suspected that the baby has suffered blood loss or the infant appears to be in shock (pale poor perfusion weak pulse) and has not responded adequately to other resuscitative measures If there is no history suggestive of blood loss shock is most likely to be due to myo-cardial dysfunction in which case fluids should be administered cautiously The most logical replacement fluid would be blood but in its absence isotonic crystalloid rather than albumin is the solution of choice given in 10 mlkg aliquots and observing the response Three randomized trials in neonates have shown
9 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
isotonic crystalloid to be as effective as albumin for the treat-ment of hypotension but none has examined either the relative or actual effectiveness in resuscitation A recent blinded randomized study comparing normal saline albumin or no volume expansion in a normovolaemic asphyxiated neonatal animal model showed that volume expansion was not beneficial and made a number of parameters worse36
NaloxoneNaloxone is not recommended as part of the initial resuscita-tion of newborns with respiratory depression Before it is given supporting ventilation should have restored the heart rate and colour The dose is 100 μgkg intravenously or intramuscularly Tracheal administration cannot be recommended Although administration of naloxone to neonates who have been exposed to maternal opioids during labour is a practice of long-standing it lacks the proper evidence of efficacy
Non-response to resuscitation
There are few more frightening situations professionally than applying the correct interventions in resuscitating or stabilizing a baby and getting no response Each stage must be adequately performed before moving onto the next and this requires regular reassessment When experienced help is needed at a newborn resuscitation it is usually the airway and ventilation that require correction If the heart rate does not increase this usually means that the lungs have not been successfully aerated In some cases however it may mean that the heart cannot respond as the cir-culation is inadequate In this situation the only way to check that the lungs have been successfully aerated is to see the chest move with ventilation or to obtain evidence of ventilation from a detector of exhaled carbon dioxide If you do not see chest movement after another five breaths the most likely cause is an obstructed airway either due to incorrect positioning or because the jaw has not been drawn forwards An oropharyngeal airway can be very helpful at this point especially in the term baby Only very occasionally is the airway blocked by mucus vernix blood or meconium but if the airway is guaranteed and there is no heart rate response or chest movement this should be sought by direct suction of the trachea even in the absence of any meconium staining of liquor Pneumothoraces can occur spontaneously after delivery but are rare at resuscitation carried out with pressure-limited devices Equally rare are diaphragmatic hernias that have not been diagnosed antenatally giving problems at resuscitation
If the chest is moving but the heart rate has not responded to resuscitation consider rare possibilities such as fetal blood loss pneumothorax or heart block (mothers with undiagnosed systemic lupus erythematosis delivered for fetal bradycardia) as possibilities With adequate ventilation there is no evidence of oxygen concentrations less than 100 being responsible for prolonged bradycardia or failure to respond although current practice would support increasing the delivered oxygen concen-tration if resuscitation had been commenced using air
Outcome
The prognosis for the full-term baby subjected to sudden acute asphyxia is usually good provided the episode does not last for
paeDiatRiCS anD CHilD HealtH 184 17
long Most babies resuscitated from primary apnoea have no sequelae secondary to the resuscitation Many babies who start to breathe again regularly within 20 min of the circulation being restored recover completely but it is rare for a baby who is still gasping after 30 min to recover
The prognosis for the preterm baby of less than about 34 weeksrsquo gestation subjected to severe acute anoxia is less predict-able This is because of the risk of secondary intraventricular haemorrhage or periventricular intracerebral haemorrhage andor infarction after even a relatively brief asphyxial episode espe-cially in the period immediately around birth
The effects of chronic hypoxia are also difficult to predict but a reasonably clear idea of the extent of the problem should be obtainable within 36ndash48 h of the original chronic asphyxial insult A mild short-lasting state of hyperexcitability usually car-ries a good prognosis even if there is seizure activity but more severe symptoms can be associated with permanent handicap This is seen especially in infants with encephalopathy requiring ventilation
REFERENCEs
1 Biarent D Bingham R Richmond S et al european Resuscitation
Council guidelines for Resuscitation 2005 Section 6 paediatric life
support Resuscitation 2005 67(suppl 1) S97ndashS133
2 international liaison Committee on Resuscitation part 7 neonatal
resuscitation Resuscitation 2005 67 293ndash303
3 Singh J Santosh S Wyllie J mellon a effects of a course in
neonatal resuscitation - evaluation of an educational intervention
on the standard of neonatal resuscitation Resuscitation 2006 68
385ndash389
4 palme-Kilander C methods of resuscitation in low-apgar-score
newborn infants - a national survey Acta Paediatr 1992 81
739ndash744
5 Kroll l twohey l Daubeney p et al Risk factors at delivery and
the need for skilled resuscitation Eur J Obstet Gynecol Reprod Biol
1994 44 175ndash177
6 Wyllie Jp Resuscitation of the newborn The Foundation Years
2007 3(4) 153ndash157
7 Richmond S ed newborn life Support Resuscitation at Birth
london Resuscitation Council 2006
8 Ceriani Cernadas Jm Carroli g pelligrine l et al the effect of timing
of cord clamping on neonatal venous hematocrit values and clinical
outcome at term a randomized controlled trial Pediatrics 2006
117 e779ndashe786
9 mercer JS Vohr BR mcgrath mm padbury JF Wallach m oh W
Delayed cord clamping in very preterm infants reduces the incidence
of intraventricular hemorrhage and late-onset sepsis a randomized
controlled trial Pediatrics 2006 117 1235ndash1242
10 Dahm lS James lS newborn temperature and calculated heat loss
in the delivery room Pediatrics 1972 49 504ndash513
11 Stephenson J Du J tk o the effect of cooling on blood gas
tensions in newborn infants J Pediatr 1970 76 848ndash852
12 gandy gm adamsons Jr K Cunningham n Silverman Wa James lS
thermal environment and acid-base homeostasis in human infants
during the first few hours of life J Clin Invest 1964 43 751ndash758
13 gluck l Kulovich mV eidelman ai et al Biochemical development
of surface activity in mammalian lung pulmonary lecithin synthesis
0 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
in the human fetus and newborn and etiology of the respiratory
distress syndrome Pediatr Res 1972 6 81ndash99
14 Vohra S Roberts RS Zhang B Janes m Schmidt B Heat loss
prevention (Help) in the delivery room a randomised controlled
trial of polyethylene occlusive skin wrapping in very preterm infants
J Pediatr 2004 145 750ndash753
15 owen CJ Wyllie Jp Determination of heart rate in babies at birth
Resuscitation 2004 60 213ndash217
16 orsquoDonnell Cp Kamlin Co Davis pg Carlin JB morley CJ Clinical
assessment of infant colour at delivery Arch Dis Child Fetal
Neonatal Ed 2007 92 F465ndashF467
17 international liaison Committee on Resuscitation part 13 neonatal
Resuscitation guidelines Circulation 2005 112(suppl 24)
iV188ndashiV195
18 leone ta Rich W Finer nn neonatal intubation Success of
pediatric trainees J Pediatr 2005 146 638ndash641
19 orsquoDonnell Cp Kamlin Co Davis pg morley CJ endotracheal
intubation attempts during neonatal resuscitation success
rates duration and adverse effects Pediatrics 2006 117
e16ndash21
20 Repetto Je Donohue pa-CpK Baker SF Kelly l nogee lm use of
capnography in the delivery room for assessment of endotracheal
tube placement J Perinatol 2001 21 284ndash287
21 gandini D Brimacombe JR neonatal resuscitation with laryngeal
mask airway in normal and low birth weight infants Anesth Analg
1999 89 642ndash643
22 esmail n Saleh m ali a laryngeal mask airway versus endotracheal
intubation for apgar score improvement in neonatal resuscitation
Egypt J Anesthiol 2002 18 115ndash121
23 Wiswell te gannon Cm Jacob J et al Delivery room management
of the apparently vigorous meconium-stained neonate results of
the multicenter international collaborative trial Pediatrics 2000
105 1ndash7
24 Vain ne Szyld eg prudent lm Wisewell te aguilar am Vivas ni
oropharyngeal and nasopharyngeal suctioning of meconium-stained
neonates before delivery of their shoulders multicentre randomised
controlled trial Lancet 2004 364 597ndash602
25 Bjorklund lJ ingimarsson J Curstedt t larsson a Robertson B
Werner o lung recruitment at birth does not improve lung function
in immature lambs receiving surfactant Acta Anaes Scand 2001 45
986ndash993
26 Bjorklund lJ ingimarsson J Curstedt t et al manual ventilation
with a few large breaths at birth compromises the therapeutic effect
of subsequent surfactant replacement in immature lambs Pediatr
Res 1997 42 348ndash355
paeDiatRiCS anD CHilD HealtH 184 17
27 taskar V John J evander e Robertson B Jonson B Surfactant
dysfunction makes lungs vulnerable to repetitive collapse and re-
expansion Am J Respir Crit Care Med 1997 155 313ndash320
28 muscedere Jg mullen JB gan K Slutsky aS tidal ventilation at low
airway pressures can augment lung injury Am J Respir Crit Care Med
1994 149 1327ndash1334
29 nilsson R grossman g Robertson B Bronchiolar epithelial lesions
induced in the premature rabbit neonate by short periods of artificial
ventilation Acta Pathol Microbiol Scand 1980 88 359ndash367
30 probyn me Hooper SB Dargaville pa et al positive end expiratory
pressure during resuscitation of premature lambs rapidly improves
blood gases without adversely affecting arterial pressure Pediatr
Res 2004 56 198ndash204
31 Wood Fe morley CJ Dawson Ja et al improved techniques
reduce face mask leak during simulated neonatal resuscitation
study 2 Arch Dis Child Fetal Neonatal Ed in press doi101136
adc2007117788
32 tan a Schulz a orsquoDonnell CpF Davis pg air versus oxygen for
resuscitation of infants at birth Cochrane Database Syst Rev 2004
(3) CD002273
33 Davis pg tan a orsquoDonnell Cp Schulze a Resuscitation of newborn
infants with 100 oxygen or air a systematic review and meta-
analysis Lancet 2004 364 1329ndash1333
34 Dawes g Fetal and neonatal physiology Chicago year Book
publisher 1968 p 141ndash159
35 Ziino aJa Davies mW Davis pg epinephrine for the resuscitation
of apparently stillborn or extremely bradycardic newborn infants
Cochrane Database Syst Rev 2003 (2) CD003849
36 Wyckoff m garcia D margraf l perlman J laptook a Randomized
trial of volume infusion during resuscitation of asphyxiated neonatal
piglets Pediatr Res 2007 61 415ndash420
Practice points
bull Resuscitation at birth is different from that at all other times
of life
bull a standard approach can be applied to most newborn
resuscitation
bull guidelines are based on a rigorous evaluation of evidence
where possible
bull evidence is sparse but evolving
bull most preterm babies require stabilization rather than
resuscitation
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Acidndashbase physiology and blood gas interpretation in the neonateSusern tan
morag Campbell
Abstractacidndashbase balance describes the complex processes that work to main-
tain a stable extracellular pH for optimal cellular function the process
of balancing the production and neutralization of tissue acid provides a
great challenge for newborn infants who have significantly higher rates
of acid production than adults Factors which help maintain a stable
acidndashbase balance include buffers the respiratory system and renal sys-
tem Both intracellular and extracellular buffers resist changes in pH
the most important extracellular buffer system for maintaining stable
pH is the bicarbonate system in response to acidosis or alkalosis the
respiratory system balances the production of acid with the clearance
of Co2 by altering respiratory rate the kidneys provide a delayed but
sustained response to pH imbalance by excreting either acidic or alkaline
urine in response to systemic acidosis and alkalosis respectively in sick
premature infants these systems have a limited capacity completely to
control pH this review discusses the physiology of the three systems
which control acidndashbase balance patterns of clinical abnormalities in
acidndashbase status and their underlying causes are discussed We present
a systematic approach to blood gas analysis and interpretation in new-
born infants
Keywords acidosis alkalosis bicarbonate bloodndashgas analysis
metabolic pH
Introduction
Blood gas analysis is a routine procedure performed on newborn babies receiving respiratory support in the neonatal intensive care The combination of invasive and non-invasive assessment of ventilation and oxygenation enables clinicians appropriately to modify respiratory care according to each individual babyrsquos rapidly changing clinical status
Understanding the fundamentals of acidndashbase balance helps us to use blood gas analysis not only to assess respiratory sta-tus but also to provide information on metabolic status and the adequacy of tissue perfusion
Susern Tan MBBS MRCP is Clinical Fellow at the Neonatal Intensive Care
Unit 6th Floor North Wing St Thomasrsquo Hospital London SE1 7EH UK
Morag Campbell MBChB MRCP is Consultant Neonatologist at the
Neonatal Intensive Care Unit 6th Floor North Wing St Thomasrsquo
Hospital London SE1 7EH UK
paeDiatRiCS anD CHilD HealtH 184 17
What is understood by acid-base balance
Acidndashbase balance refers to the complex physiological processes used by the body to maintain a stable extracellular pH1 A serum pH within the range of 735ndash745 provides the ideal environment for cellular metabolism Maintaining a stable pH is critical as the metabolic activity of proteins is pH dependent and small changes in hydrogen ion (H+) concentration can potentially alter physio-logical function
Acids are substances that yield free H+ in solution while a base accepts H+ and in solution combines with an acid to neu-tralize it In the normal metabolic state H+ are continuously pro-duced and neutralized to maintain a steady pH balance12 The rate of H+ production is two to three times higher in neonates because of their rapid growth rates and increased acid production from protein turnover and bone mineralization The challenge of maintaining a stable pH through processing and neutralizing H+ is therefore greatest in newborn infants
Using exact values of H+ concentration to assess acidndashbase status is cumbersome and it is more commonly expressed as pH defined by the equation
pH = minuslog H+
Maintaining acidndashbase balance
The balance between production and excretion of acids in the body is controlled by buffer systems which have an immediate effect and by the respiratory and the renal systems
Buffer systemsBuffer solutions resist change in pH when acid or alkali is added due to their capacity to absorb or give up H+ The three main buffer systems in the body are the bicarbonate phosphate and protein systems1ndash3 The protein and phosphate buffer systems are intracellular and act as lsquosinksrsquo for extracellular H+ which are exchanged with intracellular potassium (K+) and sodium ions (Na+) In an acute metabolic acidosis hyperkalaemia may develop due to this H+ exchange4
The bicarbonate buffer system is extracellular and consists of a mixture of carbonic acid (H2CO3) and sodium bicarbon-ate (NaHCO3) This buffer system helps maintain a stable pH by soaking up excess H+ with HCO3
minus which in solution forms carbonic acid (H2CO3) Carbonic acid is a weak acid and readily dissociates to give CO2 which is transported in dissolved form to the lungs for excretion
H+ + HCO3minus harr H2CO3 harr H2O + CO2
The bicarbonate system therefore completes the neutraliza-tion of excess H+ and a stable plasma pH is maintained The relationships between pH HCO3
minus and CO2 in this system are described by the HendersonndashHasselbalch equation15
pH = 61 + log HCO3minus003 times CO2
where 61 is the log of the dissociation coefficient of carbonic acid and 003 the solubility of CO2 in plasma Buffers are most potent when there are equal amounts of H+ and HCO3
minus in solution The
2 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
bicarbonate system is not a potent buffer however as HCO3minus
and CO2 are readily altered by the body this system plays a very powerful role in pH homeostasis15
Respiratory regulationThe respiratory system adapts within minutes to hours as part of the acute response to acidosis This system modifies pH by balancing production of H+ with ventilatory clearance of CO2
H+ directly stimulates chemoreceptors in the respiratory cen-tre of the brainstem producing an increase in respiratory rate26 The response to respiratory acidosis is very rapid as CO2 easily diffuses across the bloodndashbrain barrier however in metabolic acidosis compensation is delayed until plasma bicarbonate fully equilibrates with cerebrospinal fluid (CSF) bicarbonate There is an inverse relationship between alveolar ventilation and partial pressure of dissolved carbon dioxide (PaCO2) a reduction in alveolar ventilation raises PaCO2 and decreases pH Changes in pH therefore affect alveolar ventilation and conversely changes in alveolar ventilation cause significant changes in pH
Renal regulationThe kidneys provide a delayed but sustained response to acidndashbase imbalances by excreting either acidic or alkaline urine In full-term and preterm babies the capacity for acid excretion and bicarbonate reabsorption is reduced as glomerular filtration rates are low and tubular function immature7 Renal function matures with gestation postnatal age and glucocorticoid and thyroid hormones78 Due to their limited capacity to preserve HCO3
minus newborn infants have lower serum bicarbonate levels and are predisposed to acidosis7
Bicarbonate is not effectively reabsorbed due to its size and electrical charge Instead intraluminal HCO3
minus combines with secreted H+ in tubular luminal fluid to produce carbonic acid which dissociates to give H2O and CO2 This CO2 diffuses into tubular cells combines with intracellular H2O and forms carbonic acid which liberates HCO3
minus and H+ HCO3minus is then
recovered to the circulation by exchange for chloride ions (Clminus) through the basal cell membrane247
Renal acid secretion occurs at all sites except the loop of Henle Primary active transport accounts for 5 and secondary for the remaining 95 of total H+ excretion Secondary trans-port involves an exchange between luminal Na+ and intracel-lular H+ Both ions bind to a membrane transport protein The Na+ concentration gradient between the tubular lumen and cells enables Na+ drag into the cell which generates energy to fuel active H+ excretion into the tubular lumen1ndash47
Quantifying acidosis
Standard base excess is a calculated value derived from PaCO2 and pH It is expressed as the mmollitre of base above or below normal buffer bases required to correct the pH to 74 at a PaCO2 of 40 mmHg A negative base excess or base deficit indicates an acidosis while a positive base excess indicates a relative alkalosis15
Anion gap is the measured difference between anions and cations in the blood
Anion gap = (Na+ + k+) minus (HCO3+Clminus)
paeDiatRiCS anD CHilD HealtH 184 17
Calculation of the anion gap enables clinicians better to define the underlying cause of a metabolic acidosis9 The common causes of an increased anion gap acidosis in neonates include lactic acidosis due to tissue hypoperfusion and hypoxia it may also be seen with certain inborn errors of metabolism and in uraemia910 The anion gap can help distinguish between the rela-tively benign non-anion gap hyperchloraemic acidosis seen in premature infants and a pathological lactic acidosis due to poor end-organ perfusion1011
Strong ion theory
Stewart described a complex acidndashbase model which proposed that H+ concentration results from the dissociation of water which is influenced by PaCO2 the strong ion difference and plasma weak acids12
Strong ions are ions that dissociate at normal body pH and include Na+ K+ and Clminus Weak acids in plasma which contrib-ute include albumin inorganic phosphate and plasma proteins their concentrations do not change with pH and are therefore a constant The effect of these factors and other unmeasured tissue ions on acidndashbase status can be quantified by the calculation of the strong ion gap (SIG)112 In the neonatal unit it is perhaps more important that we consider how principles of this model may relate to acidndashbase status rather than fully to quantify the SIG Theoretically low albumin and phosphate levels which fre-quently occur in premature infants by reducing the concentra-tion of weak acids can produce a relative alkalosis while high phosphate levels in renal failure may contribute to acidosis
Tissue oxygenation
Oxygenation is closely linked to acidndashbase status as optimal cel-lular function requires oxygen to fuel aerobic metabolism and produce energy In hypoxic conditions anaerobic metabolism predominates which is energy inefficient and results in a lactic acidosis1011
Tissue oxygen availability is related to regional blood flow haemoglobin level and haemoglobin oxygen affinity Arterial blood gases measure the partial pressure of dissolved oxygen (PaO2) which represents a small component of total oxygen con-tent the majority being transported bound to haemoglobin The relationship between percentage haemoglobin saturation (SaO2) and PaO2 is described by the sigmoidal oxyhaemoglobin disso-ciation curve which enables us to relate the two measures to each other235 The affinity of haemoglobin for oxygen is altered by local tissue factors Increases in temperature H+ PaCO2 and 23-diphosphoglycerate (DPG) levels shift the oxyhaemoglobin dissociation curve to the right reducing affinity for oxygen Decreases in temperature H+ PaCO2 and 23-DPG levels shift the curve to the left increasing oxygen affinity1ndash35 In the body haemoglobin oxygen affinity continuously changes increasing in the lungs to enable efficient oxygen uptake and decreasing at tissue level to provide efficient oxygen delivery to metabolically active tissues
Avoiding both hypoxia and hyperoxia is important in the neo-natal unit as deleterious effects of hypoxia are seen in infants with pulmonary hypertension1314 while hyperoxia is associated with an increased incidence of retinopathy of prematurity1516
3 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Clinical acidndashbase imbalances
Clinical acidndashbase imbalances can be respiratory metabolic or a mixture of both These abnormalities may be corrected by the acidndashbase regulatory mechanisms in the body in an attempt to maintain normal pH (Figure 1)
Respiratory acidosisThis occurs when any disorder leads to decreased alveolar ventilation Common causes of respiratory acidosis are listed in Table 1 Reduced respiratory clearance of CO2 means more dissolved CO2 accumulates in the plasma leading to increased production of carbonic acid and H+ Through chemoreceptor stimulation respiratory acidosis rapidly alters ventilation in an attempt to reduce CO226 Chemoreceptor mediated ventila-tory increases may only partly adjust in premature infants with underlying lung disease In babies with a sustained respiratory acidosis eg in chronic lung disease then metabolic compen-sation occurs through increased renal excretion of H+ and reabsorption of HCO3
minus slowly restoring pH to around 80 of normal47
paeDiatRiCS anD CHilD HealtH 184 17
The management of PaCO2 levels in infants receiving mechan-ical ventilation has important clinical implications Premature babies have impaired cerebral autoregulation17 and adverse neurological sequelae are reported in association with high PaCO2 levels18ndash20 Ventilation strategies which advocate lsquoper-missive hypercarbiarsquo have been developed to minimize airways damage from mechanical ventilation21 Published data suggest pulmonary benefits however the safe level of PaCO2 remains to be defined in premature infants2021
Respiratory alkalosisThis occurs when more CO2 is excreted than is produced by the body Pathological conditions leading to respiratory alkalosis are rare Hyperventilation in the neonatal setting is often iatrogenic or may be due to disorders in brainstem control of breathing including hypoxicndashischaemic encephalopathy or primary central nervous system abnormalities (see Table 1)
If respiratory alkalosis is sustained it may be compensated for by reduced reabsorption of filtered bicarbonate Reported adverse associations of low PaCO2 include periventricular leuco-malacia and intraventricular haemorrhage1922
K+
H+
Overventilation
CO2 + H2O harr H2CO3 harr H+ + HCO3ndash
Bicarbonate Buffer
Intracellular Buffer
uarr H+ excretionuarr HCO3
ndash absorption
uarr buffered H+
(NH4+ H2PO4
ndash)uarr ventilation rate
RespiratoryAcidosis
MetabolicAcidosis
darr CO2and uarr pH
RespiratoryAlkalosis
MetabolicAlkalosis
darr H+ anduarr pH
darr ventilation rate
uarrCO2
and darr pH
darr H+ excretiondarr HCO3
ndash absorption
uarrH+ and
darr pH
Brain
Brain
Intracellular Buffer
H+
K+
Sepsis
HypoxiaRDS
Metabolismand growth
Diuretics
Airwayobstruction
Neuromuscularproblems
IEM
Gastric losses
+ +
ndash -
Renal BufferRespiratory Buffer
Figure 1 mechanisms for regulation of extracellular pH iem inborn errors of metabolism RDS respiratory distress syndrome
4 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Common causes of acidndashbase imbalances
pH PCO2 H2CO3 Base excess Common neonatal causes
Respiratory acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
uarr normal normal bull upper airway obstruction choanal atresia
pierre-Robin sequence
bull lung abnormalities respiratory distress
syndrome transient tachypneoa of
newborn pneumonia meconium aspiration
syndrome pulmonary hypoplasia
congenital pulmonary malformations
bull Central hypoventilation hypoxic-ischaemic
encephalopathy intracranial haemorrhage
bull neuromuscular insufficiency congenital
myopathies congenital neuropathies
bull iatrogenic inadequate ventilatory settings
Compensated lower limit
of normal
uarr uarr gt+3
metabolic acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
normal darr ltminus3 increased anion gap
bull lactic acidosis sepsis hypoperfusion
shock necrotizing enterocolitis
bull inorganic acidosis inborn errors of
metabolism renal failure
normal anion gap
bull increased gastrointestinal H2Co3 losses
ileostomy diarrhoea
bull Renal tubular acidoses
Compensated lower limit
of normal
darr darr ltminus3
Respiratory alkalosis Uncompensated gt 745 darr normal normal bull iatrogenic excessive ventilatory settings
bull Compensatory hyperventilation hypoxic-
ischaemic encephalopathy
Compensated higher limit
of normal
darr darr ltminus3
metabolic alkalosis Uncompensated gt 745 normal uarr gt+3 bull gastric losses vomiting non-replacement
of excessive nasogastric aspirates
bull thiazide and loop diuretics
bull Hypokalaemia
Compensated higher limit
of normal
uarr uarr gt+3
Table 1
Metabolic acidosisThis frequently affects infants in the neonatal unit and has many causes1011 (see Table 1) There may be overproduction of tissue acid impaired acid clearance gastrointestinal loss of bicarbonate or an exogenous increased acid load eg chloride total paren-teral nutrition (TPN) or albumin1ndash323
Calculation of the anion gap to distinguish an increased anion gap acidosis from a non-anion gap acidosis is important both for treatment and prognosis1011 Acidosis stimulates respiratory compensation but this is limited in unstable infants Similarly renal compensation with improved HCO3
minus conservation is con-strained by tubular immaturity Treatment of the acidosis should be directed at the underlying cause eg hypoxia hypotension or excess Clminus rather than by administration of base
Metabolic alkalosisThis is unusual in neonates and is most frequently seen in infants with chronic lung disease or heart failure who are receiving diuretics Diuretics cause alkalosis by increasing renal fluid and Na+ losses An active process to reabsorb Na+ occurs in tubule cells which through enhanced H+ secretion and HCO3
minus reab-sorption produce alkalosis27
paeDiatRiCS anD CHilD HealtH 184 17
Metabolic alkalosis may also occur with excessive loss of gas-tric contents eg protracted vomiting or inadequate replacement of nasogastric aspirates (see Table 1)
Interpreting blood gases
Blood gas measurements can provide important diagnostic and prognostic information and a systematic approach to blood gas analysis is described in Table 2 The clinical management of infants with abnormal gases requires a good understanding of acidndashbase physiology and tissue oxygenation and an apprecia-tion of factors which may affect the reliability of samples
Arterial blood sampling is the gold standard however indwelling arterial catheters and arterial stab samples are usually restricted to infants who are critically ill or those who require sig-nificant ongoing intervention Gases are most frequently measured in capillary or venous samples which correlate well with arterial samples for PaCO2 pH and base excess in babies and children receiving intensive care These correlations however are not valid in infants with peripheral vasoconstriction and hypotension2324
Non-invasive monitoring techniques may enable us to reduce the frequency of blood gas sampling Transcutaneous monitoring
5 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
A systematic approach to blood gas analysis
1 Collect the relevant information
bull type of gas ndash capillary or arterial
bull Current respiratory support ndash document level
bull transcutaneous Co2 and Sao2 levels
bull Clarify no significant clinical events before sampling
2 pH accept a range between 730 and 745 in newborn
babies this is lower than in older children is there an
alkalosis (pH gt 745) or an acidosis (lt 730)
3 Co2 aim for a range between 45 and 65 kpa a paCo2 level
more than 65 kpa suggests inadequate alveolar ventilation
while less than 45 kpa suggests hyperventilation Correlate
values with non-invasive measures
4 o2 Can only be assessed from arterial gases aim for pao2
between 60 and 80 kpa Correlate results with pulse
oximetry levels
5 HCo3 and base excess normal HCo3 level is between 20 and
24 mmollitre and bases excess +3 to minus3
6 anion gap look at the anion gap and lactate to help identify
the cause of an acidosis normal lactate levels should be less
than 2 mmollitre
7 Respiratory or metabolic compensation look at the pH and
assess whether it is appropriate for the Co2 level or is there
evidence of compensation
8 interpret use both the clinical history and blood gas
findings to help you identify the primary problem aim your
management at treating the underlying cause
9 Reassess if clinical management changes have been made
repeat the blood gas after an appropriate time interval to
ensure improvement
Table 2
provides a highly accurate and reliable method for measuring PaCO2 through the skin it can however be technically difficult may cause tissue damage and is of limited reliability when peripheral perfusion is reduced25 Continuous end-tidal CO2 measurements correlate well with arterial CO2 values in patients with normal ventilation and perfusion however in babies with lung disease alveolar collapse small tidal volumes and rapid respiratory rates can make these measurements unreliable26 Despite its limitations transcutaneous monitoring provides the best method for CO2 trend monitoring in the neonatal intensive care unit (NICU)25
Oxygen saturation levels can be continuously measured non-invasively using pulse oximetry While oximetry is easy to perform and accurate on occasion SaO2 levels obtained may be unreliable when tissue perfusion is poor or with movement artefact SaO2 monitoring is highly sensitive at detecting hypoxia but is limited in detecting hyperoxia as at levels more than 90 small changes in SaO2 may result in unacceptably large increases in PaO227 It is therefore essential that SaO2 alarm limits are set for all neonates receiving respiratory support to detect hypoxia and prevent hyperoxia1627
Continuous non-invasive monitoring provides invaluable information when managing complex infants in the NICU but it does not replace the need for regular blood gas analysis
paeDiatRiCS anD CHilD HealtH 184 17
ReFeRenCeS
1 Kellum Ja Determinants of blood pH in health and disease
Crit Care 2000 4 6ndash14
2 Quigley R Baum m neonatal acid base balance and disturbances
Semin Perinatol 2004 28 97ndash102
3 Brouillette Rt Waxman DH evaluation of the newbornrsquos blood gas
status Clin Chem 1997 43 215ndash221
4 Chan JC acid-base disorders and the kidney Adv Pediatr 1983 30
401ndash471
5 Siggaard-andersen o the pH-log pCo2 blood acidndashbase nomogram
revised Scand J Lab Invest 1962 14 598ndash604
6 Saetta m mortola Jp interaction of hypoxic and hypercapnic stimuli
on breathing pattern in the newborn rat J Appl Physiol 1987 62
506ndash512
7 Baum m Quigley R postnatal renal development in Seldin DW
giebisch g eds the kidney physiology and pathophysiology new
york lippincott Williams and Wilkins 2000 p 703ndash726
8 ortiz la Quan a Weinberg a et al effect of prenatal
dexamethasone on rat renal development Kidney Int 2001 59
1663ndash1669
9 gabow pa Kaehny WD Fennessey pV goodman Si gross pa
Schrier RW Diagnostic importance of an increased serum anion gap
N Engl J Med 1980 303 854ndash858
10 lorenz Jm Kleinman li markarian K oliver m Fernandez J Serum
anion gap in the differential diagnosis of metabolic acidosis in
critically ill newborns J Pediatr 1999 135 751ndash755
11 Deshpande Sa platt mp association between blood lactate and
acid-base status and mortality in ventilated babies Arch Dis Child
1997 76 F15ndash20
12 Stewart pa modern quantitative acid-base chemistry Can J Physiol
Pharmacol 1983 61 1444ndash1461
13 Dakshinamurti S pathophysiologic mechanisms of persistent
pulmonary hypertension of the newborn Pediatr Pulmonol 2005
39 492ndash503
14 mourani pm ivy DD gao D abman SH pulmonary vascular
effects of inhaled nitric oxide and oxygen tension in
bronchopulmonary dysplasia Am J Respir Crit Care Med 2004
170 1006ndash1013
15 Deulofeut R Critz a adams-Chapman i Sola a avoiding hyperoxia
in infants le 1250 g is associated with improved short- and long-
term outcomes J Perinatol 2006 26 700ndash705
16 Chow lC Wright KW Sola a Can changes in clinical practice
decrease the incidence of severe retinopathy of prematurity in very
low birth weight infants Pediatrics 2003 111 339ndash345
17 Boylan gB young K panerai RB Rennie Jm evans DH Dynamic
cerebral autoregulation in sick newborn infants Pediatr Res 2000
48 12ndash17
18 Kaiser JR gauss CH pont mm Williams DK Hypercapnia during
the first 3 days of life is associated with severe intraventricular
hemorrhage in very low birth weight infants J Perinatol 2006 26
279ndash285
19 Fabres J Carlo Wa phillips V Howard g ambalavanan n Both
extremes of arterial carbon dioxide pressure and the magnitude of
fluctuations in arterial carbon dioxide pressure are associated with
severe intraventricular hemorrhage in preterm infants Pediatrics
2007 119 299ndash305
20 thome uH Carroll W Wu tJ et al outcome of extremely preterm
infants randomized at birth to different paCo2 targets during the
first seven days of life Biol Neonate 2006 90 218ndash225
6 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
21 Carlo Wa Stark aR Wright ll et al minimal ventilation to prevent
bronchopulmonary dysplasia in extremely-low-birth-weight infants
J Pediatr 2002 141 370ndash374
22 okumura a Hayakawa F Kato t et al Hypocarbia in preterm
infants with periventricular leukomalacia the relation between
hypocarbia and mechanical ventilation Pediatrics 2001 107
469ndash475
23 peters o Ryan S matthew l Cheng K lunn J Randomised
controlled trial of acetate in preterm neonates receiving parenteral
nutrition Arch Dis Child 1997 77 F12ndash15
24 yildizda D yapiciolu H yilmaz Hl Sertdemir y Correlation of
simultaneously obtained capillary venous and arterial blood gases
of patients in a paediatric intensive care unit Arch Dis Child 2004
89 176ndash180
25 aliwalas ll noble l nesbitt K et al agreement of carbon
dioxide levels measured by arterial transcutaneous and end tidal
methods in preterm infants 28 weeks gestation J Perinatol 2005
25 26ndash29
26 Hagerty JJ Kleinman me Zurakowski D et al accuracy of a new
low-flow sidestream capnography technology in newborns a pilot
study J Perinatol 2002 22 219ndash225
paeDiatRiCS anD CHilD HealtH 184 17
27 poets CF Wilken m Seidenberg J Southall Dp von der Hardt H
Reliability of a pulse oximeter in the detection of hyperoxemia
J Pediatr 1993 122 87ndash90
Practice points
bull a stable extracellular pH is important for optimal cellular
functioning
bull abnormalities in acidndashbase balance are regulated by buffer
systems and the respiratory and renal tract
bull maintaining a stable pH is challenging for newborn babies
due to their high rates of acid production and immature
regulatory mechanisms
bull arterial or capillary blood gases provide an effective way to
monitor acidndashbase balance in newborns
bull Blood gases should be analysed in a structured manner
assessing pH and then respiratory and metabolic components
bull the treatment of acidndashbase abnormalities should be directed
at the underlying problem not merely at correcting pH
7 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Recognition and management of neonatal seizuresmalcolm levene
AbstractSeizures are the most common major manifestation of central nervous
system dysfunction in the newborn there are many causes but perina-
tal asphyxia and haemorrhagicinfarction lesions account for about 75
there is now considerable evidence that frequent but short seizures in
the neonate affect subsequent neurodevelopmental outcome Studies
using eeg or modified continuous tracing of eeg activity (aeeg or CFm)
have shown that there is often electroconvulsive dissociation this re-
fers to poor correlation between electrical seizures and clinical seizures
Commonly used anticonvulsants appear to increase electroconvulsive
dissociation effective management of neonatal seizures has proved very
disappointing and less than 50 of seizures are abolished by first-line
anticonvulsant medication (phenobarbitone or phenytoin) Drugs such
as midazolam and lidocaine may further reduce seizures but require
more evaluation the challenge is to assess new and more effective anti-
convulsants which are themselves associated with little neurotoxicity
Keywords antiepileptic drugs eeg neonatal seizures neurodegeneration
Convulsions are the most common major neurological sign seen in newborn infants and their incidence estimated from large population studies is 26 per 1000 live births1 Premature infants are over four times more likely to have convulsions than full-term infants12 Neonatal status epilepticus (continuous seizure activity lasting 30 min or more) diagnosed clinically is rare and accounts for only 5 of infants with seizures1 although this is now recognized more frequently as the result of continuous EEG monitoring3
Neonatal convulsions are described as presenting in a num-ber of different ways and various seizure types can be seen in the same baby over a number of hours The frequencies of the various patterns of seizure activity are given in Table 1 In very premature babies and to a lesser extent in term infants minor movement abnormalities may be difficult to identify as subtle seizures These include lip smacking tongue thrusting mouth-ing pedalling type movements of the lower limbs or swimming movements of the arms Apnoea can be a common manifesta-tion of subtle seizures The signs can be protean and vary from baby to baby or even in the same baby Virtually any stereotypic
Malcolm Levene MD FMedSc FRCPCH FRCH is Professor and Head of
Department of Paediatrics and Child Health at University of Leeds Leeds
and Honorary Neonatologist at Leeds General Infirmary Leeds UK
paeDiatRiCS anD CHilD HealtH 184 178
movement may be a manifestation of a seizure disorder in the newborn
Aetiology
The more carefully the fitting baby is investigated the more likely it is that a cause for the seizures will be found A number of recent papers have described the aetiology of neonatal con-vulsions after extensive investigations14 Tekgul et al4 recently studied a consecutive group of full-term infants with evidence of neonatal convulsions (recognized both clinically and on EEG) and reported their outcome Table 2 summarizes these data as well as risk of moderate or severe disability for each causative factor Perinatal asphyxia is the commonest cause for convul-sions in term infants with haemorrhagic or ischaemic lesions also being common
Overall the prognosis for the group of term babies with con-vulsions was good 72 had a favourable outcome Where asphyxia (hypoxicndashischaemic insult) is the cause of neonatal convulsions the outcome is poor in 50 The prognosis for neonatal convulsions when they were due to arterial or cere-brovenous infarction or intracranial haemorrhage was generally good Individually inborn errors are a very rare cause of neo-natal convulsions but in view of the treatable nature of some of these it is essential that these be considered and investigated appropriately5
Patterns of seizure activity in the newborn
Movement pattern Frequency ()
Clonic 50
tonic 20
Subtle 10ndash35 depending on maturity
myoclonic 5
Table 1
Cause incidence and outcome of neonatal convulsions in term infants14
Aetiological factor Incidence () Poor outcome ()
asphyxia 38ndash40 50
Cerebral arteriovenous
infarction
20 0
intracranial haemorrhage 12ndash20 13
Congenital cerebral anomaly 5ndash10 100
Hypoglycaemiahypocalcaemia 3ndash19
infection 3ndash20
inborn error of metabolism 1
unknown cause 10ndash13 0
Refers to moderate and severe neurodevelopmental abnormalitynumbers too small to make meaningful predictions
Table 2
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Controversies in the clinical management of neonatal seizures
In recent years we have learnt much more about the neurobi-ology of seizures and their effect on the developing brain The neonatal brain is in a neurophysiologically hyperexcitable state compared to the more mature brain and therefore is more prone to seizure activity This is due largely to a relative excess of GABA neuroreceptors GABA receptors are usually inhibitory but in the immature brain they have a paradoxically excitatory effect This changes at about term in primates and with progressive develop-ment they adopt a neuroinhibitory role6
The propensity to seizures in the neonatal brain makes resolv-ing the balance of risks between continuing seizure activity on the one hand against potentially adverse effects of therapy on the other a very important equation Added to this is the problem of accurately diagnosing neonatal seizures and whether commonly used anticonvulsants are successful in controlling them
These conundrums can be posed as a series of challenging questions which are discussed below
Do neonatal convulsions cause brain injuryConvulsions are a sign of neurological compromise and may indi-cate significant underlying structural brain damage or biochemi-cal disturbance which may cause further brain damage in its own right There has been considerable debate about the scale of the disability that convulsions cause the immature brain over and above that due to the underlying cause Most of our knowledge comes from studies in rodents and these have provided some tentative answers to this question
Seizures in the mature brain lead to neuronal necrosis but studies in very young rat pups whose brain development is somewhat similar to full-term infants have shown that a series of five brief seizures on five successive days does not cause struc-tural neuronal damage but does produce morphological changes in hippocampal neurones and worryingly deficits in the rat learning and visual spatial memory function in adolescent and adult life7 A single prolonged neonatal convulsion in similarly immature rats does not produce any functional effects8 Others have shown that following priming of the neonatal rat brain by short seizures as described above a further insult comprising induction of status epilepticus in the same rats at an older age causes neuronal necrosis9 This has been referred to as the lsquotwo hit hypothesisrsquo10
A more specific question is does seizure activity in an already significantly compromised brain cause additional neuropathol-ogy Wirrell et al11 studied a series of immature rat pups with the induction of an hypoxicndashischaemic (asphyxial) insult fol-lowed by either chemically-induced fits or a control sham pro-cedure In the more severely asphyxiated animals the degree of brain damage was increased significantly in those that had the additional burden of induced seizures
In summary these studies show that the immature brain is more resistant to short frequent post-seizure damage than the mature brain but despite resulting in no loss of neuronal numbers the function of the brain is permanently affected in later life In the asphyxiated brain seizures appear to have an additional adverse effect on brain damage Furthermore the immature brain that has been lsquoprimedrsquo by early seizures is more
paeDiatRiCS anD CHilD HealtH 184 179
vulnerable to status epilepticus later in life It would appear from these data that frequent seizures in the human infant should be stopped and this begs the question as to whether currently used anticonvulsants effectively control neonatal seizures
Can we rely on clinical versus EEG diagnosis of neonatal convulsionsTraditionally the diagnosis of neonatal convulsions has been made by observation and description of the frequency of abnor-mal movements EEG has been technically difficult in the hostile electrical activity of a neonatal intensive care environment and considerable expertise is required for analysis of the trace It is usually not practical to undertake traditional EEG recordings at the time the baby shows abnormal movements More recently various technological developments have allowed more direct investigation of neuronal electrical activity by either video-EEG or compressed recording of the amplitude integrated EEG (aEEG or CFM)
Rennie et al3 at Kingrsquos College Hospital London have under-taken extensive evaluation of video-EEG and have found that this technique detects many convulsions not recognized by a single channel aEEG or CFM trace Of 19 infants with evidence of convulsions on EEG only four were recognized on CFM but this may have been due to the observersrsquo lack of experi-ence with this technique In other centres that have developed appropriate expertise aEEG or CFM has proved more sensitive to the detection of seizures Video-EEG studies have also shown that many movements interpreted by experienced clinicians to be seizures are not associated with abnormal cortical activity Conversely many electrical seizures are not associated with abnormal movements This is referred to as electroconvulsive dissociation
In summary clinical observation alone to detect the fitting baby is unreliable in that it may either over-detect seizure activ-ity which is not present on EEG or under-detect clinical seizures in infants with EEG-proven convulsions The decision as to which babies to treat with antiepileptic drugs therefore becomes somewhat arbitrary
Do anticonvulsants stop neonatal seizuresAlthough neonatal seizures are common there are few random-ized controlled trials assessing the benefits of antiepileptic drugs (AEDs) in the treatment of this condition Phenobarbitone is the most widely used first-line AED and in an Australasian study 95 of neonatologists and paediatric neurologists used this drug as first-line management12 The most commonly used loading dosage is 20 mgkg but regimens of up to 40 mgkg have been recommended (Table 3)13 Four trials have evaluated the effect of phenobarbitone in abolishing neonatal seizures Two of these studies used EEG to monitor response to the drug1415 and one compared phenobarbitone with phenytoin15 In the latter study seizures were completely controlled in only 43 of babies and in the group where phenytoin was the first drug used com-plete seizure control was achieved in 45 This study switched babies from their first AED to the other if complete control was not obtained on EEG monitoring after exposure to first-line therapy In babies who had been given phenobarbitone as first-line therapy seizure control was only achieved in 57 after phenytoin was added In those given phenytoin first complete
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Dosage regimens for first- second- and third-line anticonvulsants in the neonatal period
Loading dose Second loading dose if first
unsuccessfulMaintenance dose
phenobarbitone 20 mgkg by slow iv injection 10 mgkg iv 25ndash5 mgkg od
phenytoin 20 mgkg iv over 20 min not recommended
midazolam 150ndash200 μgkg iv infusion 1 μgkgmin iv infusion increasing to 5 μgkgmin
until favourable response
lidocaine 2 mgkg iv over 10 min 6 mgkgh for 6 h iv then 4 mgkgh for 12 h then
2 mgkgh for 12 h
lorazepam 005ndash01 mgkg by slow iv injection
Diazepam 03ndash04 mgkg iv over 3ndash5 min
lidocaine should not be used if the infant has previously been treated with phenytoin
Table 3
seizure control was achieved with the adding of phenobarbitone in 62
Boylan et al14 assessed the efficacy of phenobarbitone (20ndash40 mgkg iv over 20 min) in 14 babies monitored by video-EEG in only four was there complete abolition of seizures and in the other 10 electroconvulsive seizure activity increased whereas clinical evidence of seizures reduced This has been termed elec-troclinical dissociation and anticonvulsant drug use in the new-born appears to increase this feature They also showed that the babies least likely to respond to the first-line AED are those with the most abnormal background EEG
Two studies have evaluated the use of phenobarbitone in babies who had sustained significant asphyxial insult at birth Hall et al13 compared high-dose phenobarbitone (mean 39 mgkg) versus standard dose (27 mgkg) and reported fewer convul-sions and a significant reduction of severe disability or death in the high dose group (RR 030 CI 010ndash093) A recent study from India16 of babies with hypoxicndashischaemic encephalopathy ran-domized 25 babies to phenobarbitone (20 mgkg loading dose) and compared them with 20 control babies Only 2 of 25 (4) in the phenobarbitone group developed convulsions compared with 8 of 20 (40) in the control group (p = 001) Because of the specific enrolment criteria (asphyxial insult) neither of these studies is strictly comparable to the studies by Painter et al15 and Boylan et al14 whose intention was to assess the efficacy of first-line anticonvulsant therapy on convulsions of any cause diagnosed either clinically or by EEG
Other anticonvulsants used as second- and third-line drugs have been subject to few studies in the newborn Midazolam is administered as a bolus followed by continuous infusion A recent study17 has shown that in 10 of 13 neonates given intravenous midazolam for status epilepticus control of electri-cal seizures was achieved within the first hour of treatment having been previously shown to be refractory to phenobarbi-tone treatment Some of these babies required a second bolus infusion of midazolam to obtain control of all electrographic seizures
In some parts of Europe lidocaine is used as a third-line anti-convulsant Malingre et al18 evaluated 20 infants refractory to
paeDiatRiCS anD CHilD HealtH 184 180
both phenobarbitone and midazolam and who were then given lidocaine by continuous infusion Lidocaine was effective in abolishing electroconvulsive seizures diagnosed by aEEG in 76 of the treatment courses studied No babies developed cardiac arrhythmias a previously reported complication of lidocaine in older patients As a result of pharmacokinetic studies the dosage regimen has been modified (see Table 3)
In summary phenobarbitone is effective in seizure control in less than 50 of babies and even when combined with phe-nytoin the efficacy of these drugs together remains poor More worrying is the observation that phenobarbitone tends to reduce clinically evident seizures thereby giving the clinician a false sense of security whilst having little or no effect on the num-bers of electroconvulsive disorders This has been summarized appropriately as lsquoafter all these years we still love what doesnrsquot workrsquo19 Both midazolam and lidocaine infusions appear to be effective in abolishing severe seizures in some infants resistant to phenobarbitone Lidocaine should not be given to babies previ-ously exposed to phenytoin for fear of a synergistic adverse effect on cardiac rhythm
Do antiepileptic drugs cause brain damageA riskndashbenefit analysis is needed to evaluate the efficacy of anticonvulsants in stopping neonatal seizures which is poor with standard anticonvulsants as discussed above against the risk of administering the anticonvulsant drugs themselves Phenobarbitone has been reported to have adverse effects on the developing brain including inhibition of brain growth20 neuronal toxicity21 and adverse behavioural and cognitive effects into adult life when administered to young animals22 Phenytoin shows unpredictable plasma levels and potential cardiotoxicity
Recent studies have shown an effect of AED exposure on the developing brain by causing neurodegeneration23 Phenytoin administration to immature rat pups at doses which produce serum levels similar to those achieved in human neonates was associated with widespread neuronal death as a result of apop-tosis (programmed cell death) Phenobarbitone had a similar effect when a dosage regimen similar to 40 mgkg was used and
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
this effect was maximal in the more immature brain Diazepam and clonazepam also resulted in a similar effect Midazolam and lidocaine were not tested in this study The combination of phenobarbitone or phenytoin with diazepam had a particularly profound effect on neurodegeneration
In summary recent data suggest that the commonly used AEDs for neonatal convulsions may in themselves cause neuro-degeneration due to apoptosis with lasting effects on develop-ment Many babies with neonatal convulsions are treated with at least two AEDs and this may produce more severe adverse effects than the seizures themselves
Practical management of neonatal seizures
Assimilation of these data and formulation of a rational policy is difficult when faced with a fitting neonate on an intensive care unit and pressure on the medical staff to lsquodo somethingrsquo but it is important to accept that sometimes doing nothing is preferable to using potentially dangerous drugs in a situation which does not warrant such intervention Many babies who have normal interseizure neurological clinical findings and whose seizures are relatively brief and infrequent probably do not need anticon-vulsant medication A normal or near-normal background EEG trace should reassure the clinician that anticonvulsants can be withheld
Some causes of neonatal convulsions are treatable such as meningitis hypoglycaemia hypocalcaemia and inborn errors of metabolism and each baby should be rapidly and carefully investigated for cause of the convulsions
In some babies clinical assessment of seizures is difficult ie when the baby is very sick small or paralyzed Sometimes it may be difficult to assess the significance of certain movement pat-terns Under these circumstances an EEG may prove to be very helpful In many units EEG is not available out of hours and a simple aEEG or CFM is strongly advised Modern instruments are very simple to apply and prolonged or frequent seizures should be identified with only moderate training The printout can be faxed to a more senior doctor if there is doubt as to what is shown on the trace
The balance of knowledge now is that frequent seizures cause additional damage to the developing brain and that treatment to abolish the seizures is warranted Unfortunately there is little evidence that the majority of seizures can be effectively termi-nated by current standard therapy Furthermore it appears that the more abnormal the background EEG the more difficult it is to control the seizures Nevertheless a written protocol for the management of neonatal convulsions is required on each unit Phenobarbitone and phenytoin remain the mainstay of treat-ment although their effectiveness is disappointing There is little to suggest that midazolam is more effective than lidocaine as third-line therapy but lidocaine is precluded if phenytoin has been previously used
In view of the anxiety as to the neurodegenerative effects on the immature brain of most anticonvulsants used in the neonatal period (particularly when multiple drugs are used) it is prefer-able to use only one drug to maximum dosage before introduc-ing a second In addition the duration of anticonvulsants should be minimized and the drugs stopped at the earliest opportu-nity It is my practice to stop anticonvulsants prior to discharge
paeDiatRiCS anD CHilD HealtH 184 18
from hospital if the baby is neurologically normal on clinical examination
REFEREnCES
1 Ronen gm penney S andrews W the epidemiology of clinical
neonatal seizures in newfoundland a population-based study
J Pediatr 1999 134 71ndash75
2 lanska mJ lanska DJ Baumann RJ et al a population-based study
of neonatal seizures in Fayette County Kentucky Neurology 1995
45 724ndash732
3 Rennie Jm Chorley g Boylan gB et al non-expert use of the
cerebral function monitor for neonatal seizure detection Arch Dis
Child Fetal Neonatal Ed 2004 89 F37ndashF40
4 tekgul H gauvreau K Soul J et al the current etoliologic profile
and neurodevelopmental outcome of seizures in term newborn
infants Pediatrics 2006 117 1270ndash1280
5 Surtees R Wolf n treatable neonatal epilepsy Arch Dis Child 2007
92 659ndash661
6 Ben-ari y Holmes gl effects of seizures on developmental
processes in the immature brain Lancet Neurol 2006 5 1055ndash
1063
7 Holmes gl gairsa Jl Chevassus-au-louis n et al Consequences of
neonatal seizures in the rat morphological and behavioral effects
Ann Neurol 1998 44 845ndash857
8 Stafstrom Ce Chronopoulos a thurber S et al age-dependent
cognitive and behavioural deficits following kainic-acid inducing
seizures Epilepsia 1993 34 420ndash432
9 Schmid R tandon p Stafstrom Ce et al effects of neonatal seizures
on subsequent seizure-induced brain injury Neurology 1999 53
1754ndash1761
10 Hoffmann aF Zhao Q Holmes gl Cognitive impairment following
status epilepticus and recurrent seizures during early development
support for the ldquotwo-hit hypothesisrdquo Epilepsy Behav 2004 5
873ndash877
11 Wirrell eC armstrong ea osman lD et al prolonged seizures
exacerbate perinatal hypoxic-ischemic brain damage Pediatr Res
2001 50 445ndash454
12 Carmo KB Barr p Drug treatment of neonatal seizures by
neonatologists and paediatric neurologists J Paediatr Child Health
2005 41 313ndash316
13 Hall Rt Hall FK Daily DK High-dose phenobarbital therapy in term
newborn infants with severe perinatal asphyxia a randomized
prospective study with three-year follow-up J Pediatr 1998 132
345ndash348
14 Boylan gB Rennie Jm pressler Rm et al phenobarbitone neonatal
seizures and video-eeg Arch Dis Child Fetal Neonatal Ed 2002 86
F165ndash170
15 painter mJ Scher mS Stein aD et al phenobarbital compared with
phenytoin for the treatment of neonatal seizures N Engl J Med
1999 341 485ndash489
16 Singh D Kumar p narang a a randomized controlled trial of
phenobarbital in neonates with hypoxic ischemic encephalopathy
J Matern Fetal Neonatal Med 2005 18 391ndash395
17 Castro Conde JR Borges H Domenech martinez e et al midazolam
in neonatal seizures with no response to phenobarbital Neurology
2005 64 876ndash879
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
18 malingre mm Van Rooij lgm Rademaker Cma et al Development
of an optimal lidocaine infusion strategy for neonatal seizures Eur
J Pediatr 2006 165 598ndash604
19 Sankar R painter mJ neonatal seizures after all these years we still
love what doesnrsquot work Neurology 2005 64 776ndash777
20 Diaz J Schain J Bailey Bg phenobarbital-induced brain growth
retardation in artificially reared rat pups Biol Neonate 1977 32 77ndash82
21 mattson RH phenobarbital toxicity in levy RH Dreifuss Fe
mattson RH et al eds antiepipeptic Drugs 3rd edn new york
Raven 1985 p 341ndash355
22 mikati ma Holmes gl Chronopoulos a et al phenobarbital
modifies seizure-related brain injury in the developing brain Ann
Neurol 1994 36 425ndash453
23 Bittigau p Sifringer m genz K et al antiepileptic drugs and
apoptotic neurodegeneration in the developing brain Proc Natl
Acad Sci U S A 2002 99 15089ndash15094
paeDiatRiCS anD CHilD HealtH 184 182
Practice points
bull the clinician needs to be aware that almost any repetitive
stereotype movement pattern can be a manifestation of
neonatal seizures
bull eeg is important in defining neonatal seizures
bull Frequent short-lived seizures have been shown to cause long-
term neurodevelopmental problems
bull Conventional anticonvulsant medication is ineffective in
abolishing neonatal seizures in greater than 50 of cases
bull there is evidence that exposure of the neonatal brain to
multiple anticonvulsants causes neuronal death
bull Future research is needed to evaluate more effective
anticonvulsants for treating this condition
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
Emotional support for families of sick neonatesMarina nicolaou
cristine Glazebrook
AbstractParents of sick neonates experience high levels of stress anxiety and
depression Most interventions with families of sick infants have focused
on fostering the motherndashinfant relationship through the provision of
information about infant developmental needs or through increased
motherndashinfant contact Many of these studies have reported improved
maternal well-being though there are some concerns about the scope
and practicality of large-scale interventions The few studies to have
prioritized emotional support for parents of sick neonates have pro-
duced encouraging results even interventions requiring relatively few re-
sources such as telephone support parent-to-parent support and group
support have been associated with reduced psychological morbidity for
parents The needs of parents can change throughout their infantrsquos hos-
pitalization and not all want or benefit from the provision of additional
support Thus neonatal intensive care units should aim to provide a
varied flexible and sustainable programme of support options Further
research should focus on the needs of fathers
Keywords mental health neonatal intensive care parents
The admission of an infant to neonatal care is acknowledged to be a source of considerable distress for families This review aims to explore evidence for the psychological impact on families of having an infant in neonatal intensive care and to identify evi-dence for the effectiveness of interventions to promote parental well-being It will conclude with recommendations for strategies to support parents of vulnerable infants and suggestions for fur-ther research
Psychological impact of neonatal care for parents
The majority of research examining the effect on parents of having a sick neonate has focused on families of premature or low birthweight infants Such research has found that parents with a sick neonate exhibit high levels of stress compared to normative samples and to parents of healthy full-term infants1 Singer et al2 examined the stress experienced by mothers of high-risk very low birthweight (VLBW) low-risk VLBW and term
Marina Nicolaou MPhil is a Teaching Assistant at the School of
Community Health Sciences University of Nottingham Nottingham UK
Cristine Glazebrook PhD is a Professor of Health Psychology at the School
of Community Health Sciences University of Nottingham Nottingham UK
PaeDiaTrics anD cHilD HealTH 184 196
infants Several self-report measures were used including the Brief Symptom Inventory the Parenting Stress Index (PSI) the Impact on Family Scale and the Family Inventory of Life Events and Changes (FILE) Mothers of VLBW infants had more psycho-logical distress at 1 month compared to mothers of term infants Mothers of high-risk VLBW infants also reported high psycho-logical distress at 2 years and high levels of parenting stress at 3 years Mothers have also been found to have higher stress levels compared to fathers Shaw et al3 examined the prevalence of acute stress disorder (ASD) in 40 parents whose infants were in the neonatal intensive care unit (NICU) Nearly half of the moth-ers (44) met the criteria for ASD although none of the fathers did Furthermore the severity of the symptoms (measured by the number of concurrent symptoms) was greater for the moth-ers than for the fathers3 The reasons behind this difference have been widely speculated with some believing that it is due to the mothersrsquo greater psychological involvement with the infant as evidenced by their general greater vulnerability to postpartum psychological disorder It could also reflect gender differences in coping style
Having an infant who requires intensive medical care repre-sents a significant emotional burden for families Not only is there extreme anxiety surrounding the infantrsquos health and distress for the childrsquos suffering there is also the unfamiliar and intimidating environment of the NICU to adjust to Hopper in her review of the literature identified sources of stress for parents of sick neo-nates as falling into three areas4 Situational factors included the severity of the infantrsquos illness and how parents adapted to the life crisis of having a sick infant Personal factors involved parental emotions about their roles and the instrumental and informa-tional support which were available to them The third area was classified as environmental sources of stress and included the environment of the NICU and the relationship between parents and members of staff This relationship has been examined by several studies in the nursing literature nurses are seen as ide-ally placed to provide the necessary support and information to parents with sick neonates However whilst some studies have shown that supportive and helpful hospital staff can have a posi-tive effect on parents other studies have highlighted the prob-lems and difficulties which can manifest It has been shown that parents and nurses often have very different ideas about issues eg the necessary skills and competencies needed in an NICU or the characteristics that make a lsquogood motherrsquo
Research has shown that there may be a relationship between high levels of parental stress and an increased likelihood of depression5 Postpartum depression is a psychiatric illness which appears in 10ndash15 of postpartum women Its reported preva-lence rates however have ranged from less than 10 up to 306 depending on the instruments used the population exam-ined and the timing of the research Several factors have been found to be associated with postpartum depression including poor social support and infant-related stressors6 Evidence indi-cates that postnatal depression may be underreported and this is of concern since the mental and psychological health of the mother can affect her relationship with her infant and thus the infantrsquos cognitive and emotional development5 Depressed moth-ers appear to look touch and talk to their infants less frequently and also appear to show fewer positive and more negative faces7 The vocalizations of mothers suffering with depression have also
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
been found to be less effective at promoting cognitive growth and learning in infants8
If researchers are interested in finding ways of providing sup-port for families of sick neonates then they must listen to what such families perceive their needs to be in order to avoid increas-ing anxiety and distress Furthermore the provision of appropri-ate support be it emotional informational or social will enhance parental coping abilities increase self-esteem and reduce anxiety It should be noted though that the research conducted around these issues has often taken lsquosupport needsrsquo as being synony-mous with lsquoinformation needsrsquo Such studies have examined the type the amount and quality of information that parents receive and perceive themselves as needing but have not explored in equal depth the perceived emotional support needs of families who have a sick infant In addition the needs of parents may change throughout their infantrsquos illness Ward examined the per-ceived needs of 52 parents of infants in an NICU9 Parents rated the needs of their hospitalized infant as most important along with the need to be reassured Interestingly they ranked their support needs as least important This research was conducted during the first week of the infantsrsquo hospitalization however which would explain the preoccupation of the parents with the infantrsquos health These results demonstrate that if researchers want to find ways of providing emotional support to parents of sick neonates they must be prepared not only to listen to parents but also to be flexible enough to satisfy the parentsrsquo changing needs and expectations
Interventions aimed at supporting parents
Most interventions that been evaluated in controlled studies have focused on supporting the motherndashinfant relationship and provid-ing information on infant development Many of these interven-tions have included the aim of improving the parental emotional state and thus psychological outcomes such as stress or anxi-ety have been assessed However few studies appear to include fathers This means that strategies implemented to provide emo-tional support to families of sick neonates are often derived from interventions tailored for mothers even though fathers may have different emotional needs
A wide range of interventions with mothers and infants has been evaluated in the NICU Increasing motherndashinfant contact through kangaroo care has been found to reduce maternal anxiety1011 and educational programmes delivered to fami-lies in the NICU have also been associated with reduced emo-tional difficulties in parents12ndash14 Kaaresen and colleagues implemented an intervention which consisted of eight sessions before discharge and four home visits all by trained nurses The sample included 71 premature infants in the intervention group 69 premature infants in the control group and 74 infants in the full-term control group The randomized controlled trial found that the intervention reduced parenting stress in both mothers and fathers of premature infants compared to controls to a level equivalent to parents in the term control group13 At 6 months corrected age mothers of preterm infants who had not received the intervention had total PSI scores which were 17 points higher than the mothers of infants born at term (an effect size of 057) A similar study evaluated the efficacy of an educationalndashbehavioural programmendashCreating Opportunities for
PaeDiaTrics anD cHilD HealTH 184 19
Parent Empowerment (COPE) ndash through a randomized controlled trial with 260 families of premature infants14 COPE was a four-phase educationalndashbehavioural programme which began as early as 2ndash4 d after mothers had given birth and continued until 1 week after discharge from the NICU The programme consisted of audiotaped and written infant behaviour information along with photographs which focused on common behaviours and characteristics of premature infants It also included various par-ent activities in the form of a four-phase workbook which aimed to assist mothers in the implementation of the experimental infor-mation COPE was found significantly to reduce maternal stress in the NICU as well as maternal anxiety and depressive symptoms after hospitalization In contrast a cluster randomized trial of a parenting intervention delivered to mothers of very premature infants from soon after birth showed no benefits for parenting stress1 The authors hypothesized that the intervention had not been of sufficient intensity particularly in the weeks surrounding discharge Neonatal care presents a significant barrier to parent-ing in the early weeks following a very preterm birth and so inter-ventions which focus on the developmental needs of infants and the parentndashchild relationship should particularly aim to support parents as they take on the parenting role There was also concern that the intervention had failed to reach those most at risk
Since large-scale projects can be costly to implement and may often fail to reach the families in most need it may be wiser to focus on intervention programmes which are more practical and easier to implement within a neonatal care setting Research has shown that even interventions which are based on one-off meet-ings with parents of sick neonates can be effective Jotzo and Poets examined the effect of an intervention programme aimed at reducing the severity of traumatic responses as a result of giv-ing birth prematurely15 Their programme consisted of a one-off intervention meeting along with additional psychological help throughout the hospitalization of the infant The meeting cov-ered a variety of issues including a reconstruction of the events shortly before and after the infantrsquos birth relaxation techniques discussion of coping strategies available resources and social support and support during emotional outbursts The measures used included the Impact of Event Scale (IES) and the Peritrau-matic Dissociative Experience Questionnaire At discharge the mothers who received the intervention were found to have a significantly lower traumatic impact as a result of premature birth Furthermore fewer mothers in the intervention group showed symptoms of clinically significant psychological trauma at discharge compared to mothers in the control group (36 vs 76)15 The lsquoParents Circle Programrsquo is another intervention with a similar structure16 This consisted of a 90 min session for parents with the aim of enhancing the developing relationship between parents and infants and to offer parents support A total of 104 parents (59 mothers and 45 fathers) and 44 members of hospital staff were asked to evaluate the programme and their results were analysed using content analysis Families reported gaining perspective on their situation feeling supported becom-ing aware of cues and optimizing interactions and becoming aware of available resources Parents and staff alike felt that participating in the intervention helped parents overcome the difficulties associated with the early time of their infantrsquos hos-pitalization Additional studies have also found positive results with fairly minimal interventions including discussion groups
7 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
in the NICU music during kangaroo care and pairing mothers of sick neonates with trained mothers who had been through similar experiences
Parent support programmes
Parent support programmes (PSPs) which are based in NICUs can provide parents with the opportunity to talk to parents who have been in similar situations and also to discuss their emo-tions with professionals who can help them cope with their situa-tion111718 The parent-to-parent support programme for mothers of preterm infants evaluated by Preyde and Ardal included edu-cational parental support group meetings and individual par-ent-to-parent support (primarily telephone support)19 Measures used included the Parental Stressor Scale NICU the State and the Trait Anxiety Inventories and the Beck Depression Inven-tory After 4 months of participation mothers in the intervention group reported lower levels of stress state anxiety and depres-sion compared to control group mothers The authors speculated however that the participants who were able to meet face to face with other parents were those who benefited the most Hurst conducted a comprehensive survey of an NICU-based PSP This PSP was provided in a variety of formats including a weekly parent support group hospital visitation and 24-h telephone sup-port20 Of the 477 participants 303 families used the PSP dur-ing a 2-year evaluation period with 78 using only one form of support and 18 using two forms Of a sub-sample of 48 parents asked to complete an evaluation of the PSP 92 stated that they would recommend such a programme to other parents Furthermore the majority of parents felt that it made them feel supported and helped them deal with their emotions20 This is an indication that such programmes can be very successful in sup-porting parents throughout their infantrsquos hospitalization It also shows that it can be beneficial to give parents several options and formats when it comes to such support services It is impor-tant to consider though that both the Hurst and the Preyde and Ardal studies found that some participants did not find the sup-port programmes helpful even reporting that they had caused them increased stress and anxiety Therefore it should not be assumed that support programmes will suit every individual and will provide the required support for all parents1920 NICUs need to be flexible enough to provide parents with a range of forms of support to choose from
The increased understanding of the strains that parents of sick neonates have to deal with has also led to efforts to improve customary practices in NICUs Family-centred care focuses on infants and their needs and attempts to redefine the relationship between parents and caregivers These practices strive to provide parents with support during their infantrsquos illness by focusing on freely sharing information and on the collaboration between parents and hospital staff Family-centred care has been found to be associated with several beneficial outcomes including improved parental satisfaction increased parental comfort staff satisfaction and decreased parental stress18 Research is already examining these practices and questioning how these can be improved further Such research reflects the increasing effort focused on lsquohumanizingrsquo the environment in NICUs in order to make parents feel more comfortable about spending time with their infants
PaeDiaTrics anD cHilD HealTH 184 19
Conclusion
Surprisingly few interventions have prioritized the provision of emotional support for parents of sick neonates or accounted for the changing needs and wishes of parents over the course of their infantrsquos care Large-scale supportive education-based inter-ventions have been shown to be effective in reducing parental distress However the feasibility and sustainability of such pro-grammes should also be considered Programmes which require significant additional resources can be expensive and there are also issues of training and quality control Interventions which require significant input from parents may also place additional burdens on families making them potentially less accessible to those most at risk Arguably the aim should be to explore ways of providing acceptable and effective informational support which could be complemented by emotional support from health professionals and from other parents in the unit Increasingly studies are exploring the use of computers and multimedia as an engaging flexible and cost-effective method of targeting indi-vidual needs and providing support and information Such com-puter-based and interactive multimedia interventions have been found to be successful with a range of patient groups and could therefore be examined as a complementary method of providing informational support to families with sick neonates
REfEREnCEs
1 Glazebrook c Marlow n israel c et al randomised trial of a
parenting intervention during neonatal intensive care Arch Dis Child
Fetal Neonatal Ed 2007 92 F438ndash443
2 singer lT salvator a Guo s collin M lilien l Baley J Maternal
psychological distress and parenting stress after the birth of a very
low-birth-weight infant JAMA 1999 281 799ndash805
3 shaw rJ Deblois T ikuta l Ginzburg K Fleisher B Koopman c
acute stress disorder among parents of infants in the neonatal
intensive care nursery Psychosomatics 2006 47 206ndash212
4 Hopper a sources of stress for parents of a sick neonate a
literature review Pediatr Nurs 2000 30 29ndash32
5 Davis l edwards H Mohay H wollin J The impact of very
premature birth on the psychological health of mothers Early Hum
Dev 2003 73 61ndash70
6 Bernazzani O saucier J-F David H Borgeat F Psychosocial
predictors of depressive symptomatology level in postpartum
women J Affect Disord 1997 46 39ndash49
7 Field T infants of depressed mothers Infant Behav Dev 1995 18
1ndash13
8 Kaplan Ps Bachorowski J-a Zarlengo-strouse P child-directed
speech produced by mothers with symptoms of depression fails
to promote associative learning in 4-month-old infants Child Dev
1999 70 560ndash570
9 ward K Perceived needs of parents of critically ill infants in
a neonatal intensive care unit (nicU) Pediatr Nurs 2001 27
281ndash286
10 lai Hl chen cJ Peng Tc et al randomized controlled trial of music
during kangaroo care on maternal state anxiety and preterm infantsrsquo
responses Int J Nurs Stud 2006 43 139ndash146
8 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
11 Tallandini Ma scalembra c Kangaroo mother care and mother-
premature infant dyadic interaction Infant Ment Health J 2006 27
251ndash275
12 Ohgi s Fukuda M akiyama T Gima H effect of an early intervention
programme on low birthweight infants with cerebral injuries
J Paediatr Child Health 2004 40 689ndash695
13 Kaaresen Pi ronning Ja Ulvund se Dahl lB a randomized
controlled trial of the effectiveness of an early-intervention program
in reducing parenting stress after preterm birth Pediatrics 2006
118 e9ndash19
14 Melnyk BM Feinstein nF alpert-Gillis l et al reducing premature
infantsrsquo length of stay and improving parentsrsquo mental health
outcomes with the creating opportunities for parent empowerment
(cOPe) neonatal intensive care unit program a randomized
controlled trial Pediatrics 2006 118 e1414ndash1427
15 Jotzo M Poets cF Helping parents cope with the trauma of
premature birth an evaluation of a trauma-preventive psychological
intervention Pediatrics 2005 115 915ndash919
16 Pearson J andersen K evaluation of a program to promote positive
parenting in the neonatal intensive care unit Neonatal Netw 2001
20 43ndash48
17 roman l lindsay J Boger r et al Parent-to-parent support
initiated in the neonatal intensive care unit Res Nurs Health 1995
18 385ndash394
18 Meyer ec coll cTG lester BM Boukydis cFZ McDonough sM Oh w
Family-based intervention improves maternal psychological well-
being and feeding interaction of preterm infants Pediatrics 1994
93 241ndash246
PaeDiaTrics anD cHilD HealTH 184 19
19 Preyde M ardal F effectiveness of a parent ldquobuddyrdquo program for
mothers of very preterm infants in a neonatal intensive care unit
CMAJ 2003 168 969ndash973
20 Hurst i One size does not fit all Parentsrsquo evaluations of a support
program in a newborn intensive care nursery J Perinat Neonatal
Nurs 2006 20 252ndash261
Practice points
bull Parents of sick neonates experience significant distress and
exhibit higher levels of stress anxiety and depression than
parents of healthy infants
bull educational support emotional support and increased
motherndashinfant contact have been shown to promote maternal
well-being
bull emotional support for fathers has been largely neglected in
the research literature
bull Parents benefit from a choice of supportive facilities which
could include face-to-face sessions with health professionals
telephone support hospital visitation parent-to-parent
support and unit-based group support meetings
bull Parentsrsquo support needs can change during their infantrsquos
hospitalization and not all parents want or benefit from the
provision of additional information and emotional support in
the neonatal unit
9 copy 2008 elsevier ltd all rights reserved
Personal Practice
When should enteral feeds be started in preterm infantsnicholas D embleton
AbstractPaediatricians are regularly faced with the question of when best to start
enteral feeds in preterm infants this is important as longer term out-
come may be compromised by sub-optimal nutrition in early life clinical
factors that may affect the decision to start and the risk and benefits
are discussed
Keywords breast milk feeding nutrition parenteral nutrition
Key points in the history
Alice is lsquonutritionally vulnerablersquo and whilst this may not be immediately apparent it will affect her long term outcome Her energy stores are extremely limited and consist primarily of pro-tein She has less than 5 fat and little energy associated with stored glycogen She is losing about 1 gkgd protein equivalent so she needs at least that and a minimum of 50ndash60 kcalkg of energy just to maintain the status quo let alone grow
Her weight is on the 25th centile Review of any antenatal his-tory may reveal whether fetal growth was normal Fetal growth retardation can occur with a weight greater than 10th centile The presence of antenatal absent or reversed end diastolic flow in the umbilical artery indicates poor gut blood flow This increases the risk of necrotizing enterocolitis (NEC) and might suggest a more cautious approach to starting feeds1
She has no important cardiovascular problems but if she were hypotensive gut blood flow may be low There is no umbilical
Nicholas D Embleton BSC (Hons) MBBS (Hons) MD FRCPCH is Consultant in
Neonatal Medicine at Newcastle Neonatal Service Royal Victoria
Infirmary Newcastle upon Tyne NE1 4LP UK
Should you start feeds at a day of age
alice was born following spontaneous labour at 30 weeksrsquo
gestation she weighed 1300 g and is now 18 h old she was
briefly ventilated and then extubated to continuous positive
airway pressure 12 h ago in 35 oxygen she has had caffeine
citrate but still has intermittent episodes of self-correcting
apnoea she was commenced on iv 10 dextrose but this was
replaced by a parenteral amino acid solution (referred to as
lsquotPnrsquo) along with intralipid at 0900 this morning serum glucose
is 11 mmoll and blood pressure is 42 systolic
PaeDiatrics anD cHilD HealtH 184 20
arterial catheter in situ but there is no good evidence that this should delay the decision to start feeds Her glucose is high but this is quite common in a baby like this Could this be a sign of sepsis Caffeine does not affect the incidence of NEC2 The great-est risk factor for NEC in this case is prematurity
What else might be found on examination
Up until 24 h ago she was swallowing large amounts of amniotic fluid What will have changed since then
General examination should confirm peripheral perfusion lsquogestaltrsquo view (does she look lsquowellrsquo) and cardiovascular status lsquoBowel soundsrsquo are not usually helpful
The most important variable likely to affect gut perfusion is the arterial duct Precordial lsquoheaversquo and a loud murmur are sug-gestive but it is possible to have a significant ductal shunt in a baby with a normal examination Cardiac ultrasound will con-firm this diagnosis It might be better to treat a large shunt first with indometacin and to delay starting feeds for a further 24 h
It is not possible to assess gut perfusion clinically but normal perfusion elsewhere (adequate urine output usually indicates adequate renal perfusion) would be reassuring Most preterm babies have a few abdominal lsquoloopsrsquo visible but a distended abdomen with many palpable loops suggests ileus This might be secondary to sepsis or poor gut blood flow Preterm babies do not pass much meconium in the first 24ndash48 h
Balance of risks between starting and withholding feeds
Alice requires 35ndash4 gkgd of protein and 120 kcalkgd to grow3 This will initially be provided parenterally Delaying feeds increases the risk of gut villous atrophy and prolongs the need for lsquototal parenteral nutrition (TPN)rsquo TPN requires intravenous access and so increases the risk of sepsis and when prolonged use is required combined with the lack of enteral feeding may result in hepatic impairment
Delaying feeds may allow a gut that has been chronically under-perfused to re-establish more normal perfusion although normal gut endocrine function digestive enzyme upregulation and motility require a source of intraluminal nutrients1 A recent study suggested benefit from delaying the introduction of feeds4 but methodologi-cal problems exist5 Although a Cochrane meta-analysis suggested no benefit only two studies were included6 A large UK-based trial is examining the effect of early or late feeding in preterm infants who were born growth retarded following identification of antena-tal absent or reversed end diastolic flow in the umbilical artery7
When starting feeds what volume should be used
There are no good data to guide this decision We start with 24 mlkg (1 mlkgh) and then increase by this amount each day Most babies achieve full enteral feeds (ge150 mlkgd) by a week of age Feeding guidelines improve the outcome8 Measure-ment or assessment of gastric aspirates is not consistently useful in predicting subsequent feeding intolerance or development of NEC Aspirate volumes equivalent to or sometimes greater than the amount given in the preceding 1ndash2 h are usually normal Most aspirates have a greenish colour Thick bloody or intensely bile-stained aspirates require detailed assessment
0 copy 2008 elsevier ltd all rights reserved
Personal Practice
What else affects decisions and outcome
Feeding success is affected by sepsis and NEC Scrupulous atten-tion should be paid to hand washing and intravenous access and blood sampling should be minimized There is no good evidence to support the routine use of pro-kinetic agents or H2 blockers
The most important clinical intervention affecting the occur-rence of NEC is the use of breast milk9 All efforts should be directed at persuading parents of the benefits and supporting the process Some clinicians delay starting feeds for a further 24 h whilst expressed breast milk becomes available Donor breast milk might be equally efficacious10
RefeRenceS
1 Dorling J Kempley s leaf a Feeding growth restricted preterm
infants with abnormal antenatal Doppler results Arch Dis Child Fetal
Neonatal Ed 2005 90 F359ndash363
2 schmidt B roberts rs Davis P et al caffeine therapy for apnea of
prematurity N Engl J Med 2006 354 2112ndash2121
PaeDiatrics anD cHilD HealtH 184 20
3 embleton nD Pang n cooke rJ Postnatal malnutrition and growth
retardation an inevitable consequence of current recommendations
in preterm infants Pediatrics 2001 107 270ndash273
4 Berseth cl Bisquera Ja Paje VU Prolonging small feeding volumes
early in life decreases the incidence of necrotizing enterocolitis in
very low birth weight infants Pediatrics 2003 111 529ndash534
5 Menon G Boyle eM embleton nD et al introduction of enteral
feeds in preterm infants Pediatrics 2004 114 327ndash328
6 Kennedy Ka tyson Je chamnanvanikij s early versus delayed
initiation of progressive enteral feedings for parenterally fed low
birth weight or preterm infants Cochrane Database Syst Rev 2000
cD001970
7 wwwnpeuoxacukadept
8 Patole sK de Klerk n impact of standardised feeding regimens on
incidence of neonatal necrotising enterocolitis a systematic review
and meta-analysis of observational studies Arch Dis Child Fetal
Neonatal Ed 2005 90 F147ndash151
9 lucas a cole tJ Breast milk and neonatal necrotising enterocolitis
Lancet 1990 336 1519ndash1523
10 Boyd ca Quigley Ma Brocklehurst P Donor breast milk versus
infant formula for preterm infants systematic review and meta-
analysis Arch Dis Child Fetal Neonatal Ed 2007 92 F169ndash175
1 copy 2008 elsevier ltd all rights reserved
self-assessment
Case 1A term male infant born to consanguineous parents is assessed at 24 h of age due to poor feeding profuse yellow watery diar-rhoea and irritability He weighed 32 kg at birth and delivery was uneventful There was no polyhydramnios He has been breastfed since birth On examination he is pale with a non-tender but distended abdomen and reduced bowel sounds His weight is 275 kg and he looks dehydrated Examination is otherwise normal
Initial investigations (normal values in parentheses) showed
sodium 149 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 65 mmollitre (25ndash75)
creatinine 147 μmollitre (40ndash110)
chloride 119 mmollitre (95ndash105)
haemoglobin 172 gdl (140ndash200)
White blood cell count 80 times 109litre (100ndash260)
Platelet count 302 times 109litre (150ndash400)
arterial blood gas
ph 720 (730ndash745)
PcO2 23 kPa (46ndash60)
Bicarbonate 68 mmollitre (220ndash260)
Base excess minus186 mmollitre (minus20 to +20)
lactate 59 mmollitre (06ndash24)
An abdominal X-ray shows distended bowel loops with no intramural thickening or pneumoperitoneum (Figure 1)
He was given nil by mouth and received intravenous fluids and antibiotics His dehydration improved but the metabolic acidosis and diarrhoea persisted despite receiving no enteral feeds and the commencement of total parenteral nutrition Blood and stool cultures were negative
1 Which of the following best describes these results Choose ONE answer ONLY from the followingA Hypernatraemia hyperchloraemic metabolic acidosis
with increased anion gapB Hypernatraemia hyperchloraemic metabolic acidosis
with normal anion gap
Manish Sadarangani BM BCh MA MRCPCH is Clinical Research Fellow
at the Department of Paediatrics University of Oxford Centre for
Clinical Vaccinology and Tropical Medicine Churchill Hospital
Oxford OX3 7LJ UK
Shabna Rajapaksa MB BChir MA MRCPCH is Specialist Registrar in
Paediatrics at the Paediatric Intensive Care Unit John Radcliffe
Hospital Oxford OX3 9DU UK
Nicholas Mann MD FRCP FRCPCH DCH is Consultant Paediatrician at the
Department of Paediatrics Royal Berkshire Hospital Reading RG1
5AN UK
self-assessment
C Hypernatraemic dehydration and compensated metabolic acidosis
D Acute renal failureE Renal tubular acidosis
2 What is the likely diagnosis Choose ONE answer ONLY from the followingA Hirschsprung disease ndash long segmentB Cystic fibrosis with meconium ileusC Microvillus inclusion diseaseD Cowrsquos milk protein intoleranceE Lactose intolerance
3 What is the investigation of choice Choose ONE answer ONLY from the followingA Rectal biopsy with staining for acetylcholine receptorsB Immunoreactive trypsinC Gastrointestinal endoscopy and biopsyD Stool microscopy and cultureE Stool reducing substances
Case 2A 4-year-old boy presents with a 3 d history of jaundice and a florid rash He has had orange urine and there is no change in his stool colour His family originate from Kosovo and have lived in the UK for the last 8 years He has never left the UK There is no history of blood transfusion or sex-ual abuse The grandmother was recently diagnosed with hepatitis B
On examination he is well apyrexial and mildly jaundiced with cervical and axillary lymphadenopathy He has an exten-sive papular rash over the face extremities and trunk (Figure 2) There is 3 cm hepatomegaly with no splenomegaly or ascites Examination is otherwise normal
Figure 1 abdominal X-ray of baby
Paediatrics and child health 184 202 copy 2008 elsevier ltd all rights reserved
self-assessment
Initial investigations are as follows
haemoglobin 110 gdl (113ndash135)
White blood cell count 108 times 109litre (50ndash150)
Platelet count 278 times 109litre (150ndash400)
inr 10 (08ndash12)
aPt ratio 10 (08ndash13)
sodium 140 mmollitre (135ndash145)
Potassium 42 mmollitre (35ndash50)
Urea 56 mmollitre (25ndash75)
creatinine 65 μmollitre (45ndash120)
total bilirubin 66 μmollitre (0ndash15)
conjugated bilirubin 23 μmollitre (0ndash10)
alanine aminotransferase (alt) 2033 iUlitre (0ndash35)
alkaline phosphatase 987 iUlitre (71ndash234)
Gamma-glutamyl transferase (GGt) 870 iUlitre (0ndash51)
1 What is the name of this rash Choose ONE answer ONLY from the followingA Erythema multiformeB Erythema migransC GianottiminusCrosti syndromeD EczemaE Dermatitis herpetiformis
2 What is the most likely diagnosis Choose ONE Answer ONLY from the followingA Autoimmune hepatitisB Hepatitis BC Hepatitis DD Wilson diseaseE Alpha-1 antitrypsin deficiency
3 What is the best means of management Choose ONE answer ONLY from the followingA Isolation until the jaundice disappearsB ImmunosuppressionC Copper chelating agents and genetic counsellingD Patient and family education with consideration of
antiviral agentsE Liver transplantation
Case 3A 10-month-old boy presents with 3 weeks of vomiting and constipation ndash he is passing hard stools every 2ndash3 days He has fallen from the 9th to below the 04th centile in the last 6 weeks He passed meconium within the first 24 h of life On examina-tion he looks pale and there are some dysmorphic features ndash a short nose long philtrum and wide mouth He has normal heart sounds with a grade 3 ejection systolic murmur loudest at the upper right sternal edge Examination is otherwise normal
Initial investigations are as follows
haemoglobin 91 gdl (113ndash141)
total white blood cell count 124 times 109litre (60ndash170)
Platelet count 407 times 109litre (150ndash400)
sodium 144 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 78 mmollitre (25ndash75)
creatinine 78 μmollitre (45ndash120)
albumin 52 glitre (35ndash50)
corrected calcium 384 mmollitre (238ndash263)
Phosphate 167 mmollitre (099ndash157)
1 What is the most likely diagnosis Choose ONE answer ONLY from the followingA HyperparathyroidismB Acute leukaemiaC Williams syndromeD Hypervitaminosis DE Familial hypocalciuric hypercalcaemia
2 Which investigation would be most useful in establishing the diagnosis Choose ONE answer ONLY from the followingA Intact parathyroid hormone assayB Blood filmC Fluorescent in-situ hybridization for 7q1123 deletionD 25-hydroxyvitamin D assayE Urine calciumcreatinine ratio
3 Which of the following treatments would not be suitable for this patient Choose ONE answer ONLY from the followingA Low calcium dietB Normal saline infusionC FurosemideD CorticosteroidsE Bisphosphonates
Case 4A 10-week-old girl presents with a 2-day history of poor feed-ing Her mother has been concerned about weakness since birth She only has a flicker of movement in the arms none in the legs and has a weak cry She has been passing urine and opening her bowels normally She was born at full term by normal delivery and did not require any resuscitation at birth Normal fetal movements were felt antenatally and there was no polyhydramnios She is the first child of non- consanguineous parents and there is no significant family his-tory On examination she is alert and fixing and following appropriately She has a weak cry and a weak suck There is reduced central and peripheral tone with marked head lag
Figure 2 rash found on examination
Paediatrics and child health 184 203 copy 2008 elsevier ltd all rights reserved
self-assessment
Muscle power is grade 3 out of 5 in the arms and legs There is no muscle or tongue fasciculation and she has absent reflexes throughout The remainder of the examination is normal
Electromyogram shows irregular polyphasic motor unit potentials with marked instability consistent with a dener-vating and re-innervating process (Figure 3)
1 Which of the following additional investigations may be helpful Choose ONE answer ONLY from the followingA Nerve conduction studiesB Creatine kinase assayC Muscle biopsyD SMN1 gene analysisE All of the above
2 What is the most likely cause of this childrsquos symptoms Choose ONE answer ONLY from the followingA Congenital myotonic dystrophyB Duchenne muscular dystrophyC PraderminusWilli syndromeD Spinal muscular atrophyE Mitochondrial myopathy
3 What is the mode of inheritance of this disease Choose ONE answer ONLY from the followingA X-linked recessiveB Autosomal recessiveC Autosomal dominantD MitochondrialE Sporadic
Case 5A 13-year-old girl presents with a 3-week history of fever up to 40degC night sweats and headache She has a reduced appetite with some weight loss She has no other specific symptoms She was on holiday in China 7 months ago On examination she looks well and has a temperature of 387degC There is no lymphadenopathy and no rashes Examination is entirely normal
Results of investigations are as follows
haemoglobin 126 gdl (120ndash160)
total white blood cell count 132 times 109litre (43ndash108)
neutrophil count 115 times 109litre (25ndash75)
Platelet count 244 times 109litre (150ndash400)
Blood film neutrophilia with left shift
erythrocyte sedimentation rate 63 mmh (1ndash20)
c-reactive protein 219 mglitre (0ndash5)
Blood culture Streptococcus intermedius
from anaerobic bottle only
csf culture negative
Magnetic resonance imaging (MRI) of the brain shows acute frontal sinusitis with a large intracranial frontal extra-dural empyema (Figure 4)
1 Which of the following would be appropriate management Choose ONE answer ONLY from the followingA A 12-week course of intravenous antibioticsB Drainage of the frontal sinus followed by 2 weeks of
intravenous antibioticsC Drainage of the empyema followed by 2 weeks of
intravenous antibioticsD Drainage of the empyema and the frontal sinus
followed by 2 weeks of oral antibiotics
1151
1152
1153
1154
1155
1156
1157
1158
1159
1200
50ms 1mV
Figure 3 electromyogram recording from the patient Figure 4 Parasagittal section from mri scan of patient
Paediatrics and child health 184 204 copy 2008 elsevier ltd all rights reserved
self-assessment
E Drainage of the empyema and the frontal sinus followed by 8 weeks of intravenous antibiotics
2 Streptococcus intermedius is a potential pathogen in which of the following infections Choose ONE answer ONLY from the followingA Liver abscessB Urinary tract infectionC MeningitisD Thoracic empyemaE Pneumonia
3 Which of the following statements regarding lsquopyrexia of unknown originrsquo in children is false Choose ONE answer ONLY from the followingA Malignancy is the underlying pathology in 5ndash15 of
casesB An aetiology will be found in over 90 of casesC The most common cause is infectionD A rheumatological cause is found in 10ndash20 of casesE Familial Mediterranean fever can occur in children of
non-Mediterranean ethnicity
Answers
Case 11 AThe anion gap is a useful tool to differentiate the causes of a metabolic acidosis It is calculated by the equation
Anion gap = [Na K ] [Cl HCO ]3+ + minus minus+ minus +
It represents the effect of unmeasured anions on the plasma pH and is normally 10ndash18 mmollitre
2 CMicrovillus inclusion disease is a severe autosomal recessive enteropathy that is typically apparent within hours or days after birth It is the second most common cause of protracted diarrhoea in the newborn after infectious causes It is characterized by severe yellow watery diarrhoea and malabsorption due to hypoplasia andor atrophy of the villi of the small intestine secondary to an inherited defect in the brush border membrane This results in severe dehydration malnutrition and metabolic acidosis due to bicarbonate loss from the gut
3 CDiagnosis of microvillus inclusion disease is made on small bowel biopsy Electron microscopy findings are of intracellular brush border inclusions and densely packed apical cytoplasmic vesicular bodies indicating microvillous atrophy There is no cure Treatment is supportive with total parenteral nutrition and consideration of small bowel transplantation
Further reAding
Goulet O ruemmele f causes and management of intestinal failure
in children Gastroenterology 2006 130(suppl 1) s16ndash28
rhoads Jm Vogler rc lacey sr et al microvillus inclusion disease
In vitro jejunal electrolyte transport Gastroenterology 1991
100 811ndash817
Case 21 CGianottindashCrosti syndrome is a distinct self-limiting rash commonly associated with viral infections in children between 2 and 6 years of age It presents as multiple pink to redminusbrown papules or papulovesicles which may be pruritic and can become confluent Gianotti and Crosti initially described the exanthema as associated with hepatitis B virus and they termed it papular acrodermatitis of childhood It can occur in several viral diseases eg hepatitis A B and C coxsackie viruses and cytomegalovirus
2 BHepatitis is a syndrome characterized by inflammation or injury of liver cells which may develop into cell necrosis and subsequently fibrosis andor cirrhosis Biochemically there are raised liver enzymes The degree of transaminase elevation does not correlate with the severity of the disease process Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of viral hepatitis
3 DHepatitis B infection is transmitted via blood sexually or vertically Infection may be acute or chronic Diagnostic markers are the presence of surface antigen (HBsAg) and HBV DNA The presence of e antigen (HBeAg) indicates high infectivity Infected newborns have a 95 risk of becoming carriers this risk decreases with infection acquired later in childhood Approximately 15ndash25 of HBV carriers will die from cirrhosis or hepatocellular carcinoma Extrahepatic findings are more common in older children and include membranous glomerulonephritis and GianottiminusCrosti syndrome Fulminant hepatic failure occurs in severe cases resulting in persistent jaundice encephalopathy and coagulopathy Management includes counselling family members monitoring for ongoing liver disease and consideration of antiviral therapy
Further reAding
Brandt O abeck d Gianotti r Burgdorf W Gianotti crosti
syndrome J Am Acad Dermatol 2006 54 136ndash145
slowik mK Jhaveri r hepatitis B and c viruses in infants and
young children Semin Pediatr Infect Dis 2005 16 296ndash305
Case 31 CHypercalcaemia is uncommon in infancy The most common symptoms in this age group are irritability vomiting and constipation It may be a manifestation of Williams syndrome vitamin D or calcium excess as well as disorders associated with reduced bone formation such as hypophosphatasia or increased bone resorption such as malignancy Occasionally
Paediatrics and child health 184 205 copy 2008 elsevier ltd all rights reserved
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-
SympoSium neonatology
mainstay of prevention For babies who are able to feed orally breast feeding should be first choice and there must be maximal support for the mother to do so This is a key clinical priority for midwives and paediatricians
If there are concerns regarding adequacy of breast feeding to prevent hypoglycaemia the mother should be encouraged to commence expression of milk from very soon after birth If there is insufficient breast milk to prevent babies reaching the opera-tional thresholds described above there should be judicious use of formula milk using only the smallest amount required to keep the babyrsquos glucose in the required range Formula milk in exces-sive quantities has been demonstrated to suppress normal meta-bolic adaptation2122
In babies for whom early enteral feeds are not appropriate or not tolerated or for whom enteral feeding does not prevent blood glucose level falling below operational thresholds intravenous glucose infusion at rates around 4ndash5 mgkgmin (58ndash72 mlkgd of 10 dextrose) are usually sufficient to prevent hypoglycae-mia If blood glucose levels remain below therapeutic goals the rate of infusion may be steadily increased Excess glucose infu-sion over and above that required to maintain the therapeutic goal will stimulate insulin and there is a risk of rebound hypo-glycaemia if high rate glucose infusions are too rapidly reduced Milk feeds if tolerated should be continued if intravenous glu-cose is commenced
If infused volume of glucose solution becomes excessive in order to maintain therapeutic goals or if fluid restriction must be applied more concentrated glucose concentrations must be infused through a central venous line This is particularly rel-evant to the hyperinsulinaemic baby in whom glucose infusion rates in excess of 8ndash10 mgkgmin are required to maintain ther-apeutic goals There is a high risk of severe and brain-damaging hypoglycaemia if treatment is delayed or fails to raise blood glu-cose levels and management of these babies requires consulta-tion with or referral to a specialist centre24
If there is presentation of hypoglycaemia with abnormal clinical signs or a very low blood glucose level (less than 1 mmollitre) this mandates urgent treatment with intravenous glucose The rates of glucose infusion described above are usually sufficient to bring the blood glucose level rapidly to the therapeutic goal without a bolus of glucose being necessary In fact a bolus dose of glucose will result in a peak blood glucose level and then an insulin surge making subsequent management problematical This is minimized by the use of a lsquomini-bolusrsquo should a bolus of glucose be required ndash 200 mg glucosekg (2 mlkg of 10 dextrose)28 Indications for mini-bolus are infants presenting with fits or coma or an lsquounre-cordablersquo or zero blood glucose level A mini-bolus should always be followed with glucose infusion or an increased glucose infusion rate if a baby already receiving intravenous glucose has required a mini-bolus
The temptation to supplement enteral feeds with glucose polymers and energy supplements (eg Duocal) or to use oral glucose gels or solutions (eg Hypostop) should be avoided as this carries a risk of necrotizing enterocolitis is likely to suppress normal metabolic adaptation and will suppress the appetite of the baby for effective oral feeding
Finally there are additional medications which may be employed in specific circumstances (Table 4) More detailed descriptions are given elsewhere242728 Babies who have hypoglycaemia which
paeDiatRiCS anD CHilD HealtH 184 164
is difficult to control by the measures described above and who require these additional treatments should be cared for in a centre which has expertise in metabolic and endocrinological conditions
Summary
Much controversy and confusion has surrounded neonatal hypo-glycaemia but this usually arises as a result of failure to under-stand the processes of normal metabolic adaptation and the fact that hypoglycaemia is a presenting sign rather than a diagnosis in itself Plans for investigation and management must be based upon the most likely underlying cause of impaired metabolic adaptation and take into account the clinical condition of the baby This is counter to the current trend to propose rigid pro-tocols and algorithms and re-introduces the value of detailed clinical evaluation and decision making The mainstay of man-agement is close clinical observation of vulnerable infants and energy provision tailored to their individual needs whilst avoid-ing excessively invasive management (namely unnecessary sep-aration of mother and baby routine or excessive formula milk supplementation or intravenous glucose administration) which themselves inhibit protective metabolic responses and impede successful establishment of breast feeding
ReFeRenCeS
1 Cornblath m Hawdon Jm Williams aF et al Controversies regarding
definition of neonatal hypoglycemia Suggested operational
thresholds Pediatrics 2000 105 1141ndash1145
2 Cornblath m ichord R Hypoglycemia in the neonate Semin
Perinatol 2000 24 136ndash149
3 Vannucci RC Vannucci SJ Hypoglycaemic brain injury Semin
Neonatol 2001 6 147ndash155
4 Rozance pJ Hay WW Hypoglycaemia in newborn infants features
associated with adverse outcomes Biol Neonate 2006 90 74ndash86
5 Hawdon Jm Hypoglycaemia in newborn infants defining the
features associated with adverse outcomes ndash a challenging remit
Biol Neonate 2006 90 87ndash88
6 Williams aF neonatal hypoglycaemia clinical and legal aspects
Semin Fetal Neonatal Med 2005 10 363ndash368
7 Soothill pW nicolaides KH Campbell S prenatal asphyxia
hyperlacticaemia hypoglycaemia and erythroblastosis in growth
retarded fetuses BMJ 1987 294 1051ndash1053
Additional medication in specific conditions (if these are required there must also be referral to a specialist centre)
Medication Indication
glucagon intramuscular bolus dose of 200 μgkg
transient rise in blood glucose level eg
when difficulty re-siting intravenous infusion
Diazoxide Hyperinsulinism
Hydorcortisone pituitary or adrenal insufficiency
Table 4
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
8 Hawdon Jm Ward platt mp mcphail S Cameron H Walkinshaw Sa
prediction of impaired metabolic adaptation by antenatal Doppler
studies in small for gestational age fetuses Arch Dis Child 1992
67 787ndash792
9 Deshpande S Hawdon Jm et al adaptation to extrauterine life in
Rodeck C Whittle m eds Fetal medicine Basic Science and Clinical
practice edinburgh Churchill livingstone 1999
10 Ward platt m Deshpande S metabolic adaptation at birth Semin
Fetal Neonatal Med 2005 10 341ndash350
11 eyre Ja Stuart ag Forsyth RJ Heaviside D Bartlett K glucose
export from the brain in man evidence for a role for astrocytic
glycogen as a reservoir of glucose for neural metabolism Brain Res
1994 28 349ndash352
12 Hawdon Jm Ward platt mp aynsley-green a patterns of metabolic
adaptation for preterm and term infants in the first neonatal week
Arch Dis Child 1992 67 357ndash365
13 Hawdon Jm Ward platt mp aynsley-green a prevention and
management of neonatal hypoglycaemia Arch Dis Child Fetal
Neonatal Ed 1994 70 F60ndash64
14 Hawdon Jm Hypoglycaemia and the neonatal brain Eur J Paediatr
1999 158 S9ndash12
15 massieu l Haces ml montiel t Hernaacutendez-Fonseca K acetoacetate
protects hippocampal neurons against glutamate-mediated neuronal
damage during glycolysis inhibition Neuroscience 2003 120
365ndash378
16 yamada Ka Rensing n thio ll Ketogenic diet reduces
hypoglycaemia-induced neuronal death in young rats Neurosci Lett
2005 385 210ndash214
17 nehlig a Brain uptake and metabolism of ketone bodies in animal
models Prostaglandins Leukot Essent Fatty Acids 2004 70
265ndash275
18 Hernaacutendez mJ Vannucci RC Salcedo a Brennan RW Cerebral blood
flow and metabolism during hypoglycemia in newborn dogs
J Neurochem 1980 35 622ndash628
19 Vannucci RC nardis ee Vannucci SJ Campbell pa Cerebral
carbohydrate and energy metabolism during hypoglycaemia in
newborn dogs Am J Physiol 1981 256 H1659ndashH1666
20 anwar m Vannucci RC autoradiographic determination of regional
cerebral blood flow during hypoglycaemia in newborn dogs Pediatr
Res 1988 24 41ndash45
21 Hawdon Jm Williams aF et al Formula supplements given to
healthy breastfed preterm babies inhibit postnatal metabolic
adaptation results of a randomised controlled trial Arch Dis Child
2000 82 a30
paeDiatRiCS anD CHilD HealtH 184 16
22 de Rooy l Hawdon Jm nutritional factors that affect the postnatal
metabolic adaptation of full-term small- and large-for gestational
age infants Pediatrics 2002 109 e42
23 Hawdon Jm Hypoglycaemia and brain injury ndash when neonatal
metabolic adaptation fails in levene m ed Fetal and neonatal
neurology and neurosurgery edinburgh Churchill livingstone in
press
24 Hussain K Congenital hyperinsulinism Semin Fetal Neonatal Med
2005 10 369ndash376
25 acolet D Diabetes in pregnancy Caring for the Baby after Birth
CemaCH 2007 2
26 Hussain K Sharief n the inaccuracy of venous and capillary blood
glucose measurement using reagent strips in the newborn period
and the effect of haematocrit Early Hum Dev 2000 57 111ndash121
27 Hawdon Jm Disorders of blood glucose homeostasis in the neonate
in Rennie Jm ed Robertonrsquos textbook of neonatology 4th edn
edinburgh Churchill livingstone 2005
28 Deshpande S Ward platt mp the investigation and management
of neonatal hypoglycaemia Semin Fetal Neonatal Med 2005 10
351ndash361
Practice points
bull identify risk factors for impaired metabolic adaptation
bull Clinical monitoring including accurate blood glucose
measurement for at-risk babies
bull Feed at-risk babies soon after birth and maintain thermal
homeostasis
bull take first blood glucose level at 3ndash4 h of age
bull intervene in at-risk baby with no clinical signs if two
consecutive blood glucose measurements lt 20 mmollitre
bull intervene in any baby with blood glucose measurement
lt 10 mmollitre
bull intervene in any baby with abnormal clinical signs regardless
of blood glucose level
bull investigate for underlying cause of failure of metabolic
adaptation
bull maintain lactation and breast feeding
5 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Resuscitation of the term and premature babyJonathan Wyllie
Abstractalthough most newly born babies establish normal respiration and
circulation without help up to 1minus2 may require some resuscitation
or stabilization Babies who do not establish adequate regular normal
breathing or who have a heart rate of less than 100 beatsmin or other
problems such as prematurity may require assistance the differences in
approach to the resuscitation of such babies originate in the physiology
and pathophysiology of acute asphyxia at birth However management
of airway and breathing remain the key features of resuscitation and
where cardiac depression has occurred this is nearly always due to hy-
poxia secondary to respiratory compromise therefore most babies will
respond within 2minus3 min of effective aeration of the lungs and the need
for intubation chest compressions or drugs is rare the international
liaison Committee on Resuscitation (ilCoR) evaluated evidence in 2000
and 2005 in order to provide guidelines for resuscitation they will do
so again for 2010 this evidence is limited in terms of both quantity and
quality and controversies still exist more research is needed to ensure
that our future actions are based upon evidence rather than history this
article will review the recommended approach to resuscitation as well as
some newer evidence
Keywords guidelines neonatal newborn premature resuscitation
Background
In the UK 669 601 babies were born alive in 2006 and most made the transition to extrauterine life without problems Those babies who did not establish adequate regular normal breathing or who had a heart rate of less than 100 beatsmin may have required assistance1 Factual evidence concerning the true requirement for resuscitation at birth is sparse Up to 10 of newborns may require some assistance to begin breathing with less than 1 needing extensive resuscitation2 However just because a baby received resuscitation does not necessarily mean that it was required and rates of intervention may be altered by educa-tion34 or the personnel present at deliveries5 In a UK tertiary centre with a standard approach to resuscitation at birth up to 12 of all babies received some airway assistance with just over 1 being intubated3 In Sweden only 1 of babies over 2500 g required mask or endotracheal tube ventilation at birth of which most responded to the former4
Jonathan Wyllie MBChB FRCPCH is Consultant Neonatologist at the James
Cook University Hospital Marton Road Middlesbrough TS4 3BW UK
paeDiatRiCS anD CHilD HealtH 184 16
Sometimes it is possible to predict babies who are likely to have respiratory depression at birth and to have appropriate per-sonnel present at delivery Guidelines for attendance at deliveries will vary with institution but even when almost 40 of deliv-eries are attended there may still be a further 15 of babies who require unexpected resuscitation5 a proportion that seems to remain whatever changes are made
The physiology of babies requiring help at birth has been summarized previously167 It allows a logical approach to resus-citation (Figure 1) when evidence is lacking and may prompt further research
Resuscitation at birth
PreparationAt birth resuscitation is more likely in babies with intrapartum evidence of significant fetal compromise those less than 35 weeksrsquo gestation those delivering vaginally by the breech and in multiple births Personnel trained in newborn resuscitation should be available at every delivery1 Someone experienced in tracheal intubation and advanced resuscitation should also be easily available for normal low-risk deliveries in hospital and ideally in attendance for deliveries with an increased likelihood of needing resuscitation In the latter cases the equipment and environment can be prepared beforehand including a discussion with the parents Wash your hands put on gloves and consider what help may be needed
Cord clampingAt birth it has long been known that delay in clamping the cord will lead to less anaemia in babies and reduce subsequent iron deficiency8 However few hospitals have practised this interven-tion due to worries about hypothermia and the need to resusci-tate or stabilize babies In developed countries the advantages seemed to be outweighed by the potential disadvantages A recent randomized controlled study of delayed clamping of the cord in premature babies found that the intervention group had less late-onset sepsis and fewer intraventricular haemorrhages9 This is a low-risk strategy which needs further evaluation in order to introduce it without increasing other risk factors in pre-mature deliveries
Assessment and temperature controlAssessment and temperature control for the newborn baby should occur at all deliveries The assessment indicates the need for resuscitation Babies may vary from 23 to 40+ weeksrsquo ges-tation and in weight from 500 to 5000 g They are born naked and wet and if left cannot cope with an environmental tem-perature of less than 32degC However if the term baby is imme-diately dried put skin-to-skin with the mother and covered the delivery room temperature can be as low as 25ndash28degC Obviously the smaller the baby the greater the surface area to mass ratio and the greater the risk of hypothermia Compromised babies are particularly vulnerable10 and hypothermia will lower oxygen tension11 increase metabolic acidosis12 and inhibit surfactant production13
An effective method of maintaining the temperature of prema-ture babies less than 28 weeksrsquo gestation is wrapping them with plastic before drying and then placing them under a radiant
6 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Dry the babyRemove any wet towels and cover
Start the clock or note the time
Give 5 inflation breathsLook for a response
If no increase in heart rate look for chest movement
Re-check head positionApply Jaw thrust
Repeat inflation breathsLook for a response
If no increase in heart rate look for chest movement
Try alternative airway opening manoeuvresRepeat inflation breaths
Look for a response
If no increase in heart rate look for chest movement
If the heart rate is not detectable or slow (lt60)Start compressions
3 compressions to each breath
Reassess heart rate every 30 secondsConsider venous access and drugs
Assess colour tone breathing and heart rate
Open the airway
If not breathing
If still not breathing
If no response
If still no response
When the chest is moving
If meconium present
Baby breathing wellDo not suction the airway
Baby floppy and not breathing wellConsider inspection and suction before
inflation breaths
Head in neutral position
Inflation breathsUse a well-fitting face mask
connedted to a
pressure-limited gas supply
Each breath 2ndash3 seconds
duration at 30 cm H2O for a
term baby
Get help from a second personto support the airway andor
inspect the oropharynx under
direct vision and consider
suction andor insert an
oropharyngeal airway
Chest compressionsCompvent ratio 31
Rate 120 events per minute
Ensure the chest moves with each ventilation breath
If breathingReassess heart rate and monitor baby
If heart rate is satisfactory but increasingContinue ventilation breaths at about 30 per
minute until baby is breathing adequately
If heart rate is satisfactory but increasingContinue ventilation breaths at about 30 per
minute until baby is breathing adequately
If heart rate is increasingStop compressions
Continue ventilation breaths at about 30 per
minute until baby is breathing adequately
If the chest is not movingRecheck head position and repeat inflation
breaths If competent consider intubation
If the chest is still not movingThe airway is the problem
Figure 1 newborn life support (Courtesy of the Resuscitation Council uK)
heater14 There is a small risk of hyperthermia so the temperature must be monitored carefully
An assessment is made of the babyrsquos colour tone respira-tions and heart rate127 The most important of these is heart rate and a stethoscope is more reliable than cord pulsation15 How-ever saturation monitors may offer a more reliable assessment of both heart rate and colour16 but their interpretation requires a detailed knowledge of normal saturations at birth at differing gestations A baby who is apnoeic and floppy in the absence of neurological disease is unconscious and likely to be in terminal apnoea however this does not change the initial approach other
paeDiatRiCS anD CHilD HealtH 184 167
than the need to summon help early APGAR scores are never calculated to guide resuscitation
Airway
If a baby is in primary apnoea then with an open airway the first gasp will start to aerate the lungs and most babies will be able to lsquoresuscitatersquo themselves as shown in physiological stud-ies on animals Neutral positioning of the babyrsquos head chin lift jaw thrust oropharyngeal airways and endotracheal intubation may all be helpful in certain situations if performed correctly17
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Endotracheal intubationThe placement of an endotracheal tube has long been the gold standard of airway control and this remains true in the unconscious baby if it is correctly sized placed and fixed in a timely manner However experience is directly related to effec-tiveness in endotracheal intubation1819 and the success rate of less experienced clinicians such as a resident (STA1-3) or a fel-low (STA3-5) is lower varying between 33 and 68 Even senior neonatologists often take longer than guidelines recom-mend19 Experienced clinicians may judge correct endotracheal position visually or by an increase in heart rate with the first breaths but detection of exhaled carbon dioxide will give more rapid confirmation in larger babies12171920 and this can be par-ticularly useful for less experienced clinicians or those supervis-ing them However not all systems for the detection of exhaled carbon dioxide work in the smallest premature infants
Laryngeal masksLaryngeal masks may be effective for ventilating term newborn babies but there are few data for small premature infants There have been reports of dislodged laryngeal airways during paedi-atric arrests when chest compressions have been administered Although success of placement at first attempt by paediatri-cians is greater with a laryngeal mask than with an endotra-cheal tube21 the only and small randomized controlled trial in the delivery room favoured endotracheal intubation when per-formed by an anaesthetist22 Based mainly upon case reports the laryngeal mask can be recommended when positioning and mask ventilation and endotracheal intubation have failed to secure the airway but not as yet as a primary method of airway control
MeconiumIn 2000 Wisewell et al23 reported a large randomized controlled trial showing that tracheal intubation and suctioning of meco-nium-stained but vigorous babies at birth did not reduce the incidence or severity of meconium aspiration syndrome More recently another randomized trial has now shown that suction-ing on the perineum similarly offers no benefit24 Neither of these practices is recommended but intubation and suction of meconium from the trachea of non-vigorous babies born through meconium-stained liquor is still recommended
Breathing
In the apnoeic baby the first breaths establish the resting lung volume and aerate the fluid-filled alveoli This mechanical effect aided by surface tension within the alveoli causes the initial fall in pulmonary vascular resistance Experimentally this effect occurs even if the lungs are ventilated with nitrogen but is increased when air is used presumably due to the vasodilator effect of 21 oxygen The mechanical stretching of the lung also triggers the activation of cyclo-oxygenase beginning the production of prostacyclin Bradykinin is produced which has a further direct vasodilator effect and also possibly via prostacyclin Therefore adequate airway control and passive ventilation is vital not only because babies requiring resuscitation at birth have an almost uniformly respiratory aetiology but also in order to promote post-natal adaptation and reverse any maladaptation
paeDiatRiCS anD CHilD HealtH 184 16
In term babies peak ventilatory pressures of 20ndash30 cmH2O may be required but the minimal pressure needed to achieve an improvement in heart rate should be used or if there is no response chest wall movement Longer breaths at lower pressure may be more effective in displacing alveolar fluid and establish-ing the resting lung volume in lungs with sufficient surfactant and may improve initial oxygenation However premature new-borns are obviously physiologically and anatomically less pre-pared for delivery than infants at term Over-inflation has been implicated in histological lung damage in animal models and high tidal volumes appear to be equally damaging whether given before or immediately after administration of surfactant How-ever the same effect is not seen if these excessive tidal volumes are delivered 15 min after administration of surfactant2526 It is now thought that both excess end expiratory volume and inad-equate end-expiratory volume may cause lung damage2728 In premature infants it would therefore seem sensible to use lower pressures of 20ndash25 cmH2O12 delivered in a controlled way to prevent over-inflation and to apply positive end-expiratory pres-sure (PEEP) to prevent damage from under-inflation PEEP also improves both lung compliance and gas exchange2930 Without PEEP the airways collapse during the expiratory phase in animal models of newborn resuscitation
If animal data can be extrapolated it would also seem appro-priate to give surfactant as soon as possible to premature babies in order to ameliorate damage2526
The majority of newborn infants requiring resuscitation will re-establish regular respiration after administration of a few breaths which may be due to Headrsquos paradoxical reflex by which the inflation triggers an inspiratory effort
VentilationOnce the lungs are aerated if the newborn remains apnoeic ventilation should be continued at 30ndash60 breathsmin avoiding hyperventilation and using the minimum pressure possible to maintain a heart rate greater than 100 beatsmin
Face mask the majority of infants who require ventilation receive it via a face mask This may be attached to a bagvalve system with a spring lsquoblow offrsquo system or a lsquoT-piecersquo with a set flow and pressure It is important to realize that the bagvalve system is flow sensitive and that the harder the operator presses the greater the flow and the higher the delivered pressure In fact 60 cmH2O can be achieved with vigorous squeezing of a self-inflating bag Therefore it may be advantageous that most opera-tors are unlikely to be as effective as they suppose in creating a seal with the mask31 This is a skill that requires tuition and prac-tice31 In delivering a set pressure T-piece systems such as the Tom Thumbcopy or Neopuffcopy perform better than any bagminusvalve system but require a gas supply There is no evidence that lung compliance can be assessed using any bag system
Continuous airway pressure case series have suggested that early or delivery room use of continuous positive airway pres-sure (CPAP) in premature babies may reduce chronic lung dis-ease There have been two randomized trials of which one was a pilot study The data from the COIN trial do not show any advan-tage other than a reduction in intubation and surfactant use in the intervention group However an excess of pneumothorax
8 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
was also reported The Vermont Oxford Network and the SUP-PORT trials will provide further data but at present the delivery room use of CPAP cannot be widely recommended and should be limited to those units experienced in its use or taking part in research
Air or oxygen oxygen has been in widespread use for resuscita-tion at birth since the 1930s and even hyperbaric oxygen was seriously supported in the 1960s For many years there have been concerns about tissue damage from oxygen deprivation during and after resuscitation It became evident in the 1950s that unrestricted oxygen therapy could have serious conse-quences for future vision More recently concerns have been raised about potential adverse effects on respiratory physiology cerebral circulation and tissue damage from oxygen free radicals even during resuscitation A meta-analysis of four human studies demonstrated a reduction in mortality and no evidence of harm in infants resuscitated in air versus 100 oxygen3233 However there are several significant methodological concerns with these studies and the results should be interpreted with caution There is insufficient evidence to recommend any specific concentration of oxygen to be used for newborn resuscitation Monitoring the oxygen saturation of babies may be helpful but as yet there are no time-related normal target ranges and healthy term babies may take up to 10 min to achieve preductal oxygen saturation of greater than 95 and up to 60 min to achieve this postductally
There is therefore equipoise which would be open to an appropriate randomized controlled trial In the meantime the evidence only supports use of either 21 or 100 oxygen It is provoking to realize that if air had been in constant use since the 1930s there would be insufficient evidence for use of supple-mental oxygen
Circulation
Early resuscitation (temperature control airway breathing) provides oxygenated blood in the pulmonary arterioles which if returned to the heart causes the rate to increase34 If due to acidosis and hypoxia the circulation is ineffective then chest compressions may be needed They should be commenced when the heart rate remains below 60min despite effective airway and breathing management127 The best technique is using two hands to encircle the chest1 A ratio of three compressions to one breath is internationally accepted127 but has no evidence to support it Research has shown that neither compressions nor drugs will work in this situation without oxygenated blood so effective lung aeration and ventilation is essential A logical approach would be to fill the alveoli with air and to compress the chest until they are empty However training and teamwork require an agreed ratio which has therefore not changed since guidelines were first agreed internationally Success is assessed by an increase in heart rate which should therefore be assessed every 30 s Compressions stop when the spontaneous heart rate is greater than 60 beatsmin
In hypoxic newborn animal models successful resuscitation can restore cardiac output and blood pressure to levels above baseline within 5ndash10 min However it should be noted that there is a decline to 30 lower than basal levels within 2 h and that blood pressure is relatively spared suggesting an even greater
paeDiatRiCS anD CHilD HealtH 184 16
reduction in tissue perfusion This should be considered in the later care of any neonate who was hypoxic at birth
Drugs
Neonatal bradycardia at birth is almost always due to hypoxia plusmn acidosis and therefore drugs are rarely needed Adrenaline (epi-nephrine) is reported as being used in between 1 and 4 babies per 2000 births which is a large variation in practice Reported success is also variable and must be interpreted in light of this variation The use of drugs in extremely premature infants is con-troversial Some data suggested good outcomes for babies below 28 weeksrsquo gestation given adrenaline but these were flawed by high numbers of babies receiving resuscitative drugs some before the airway had been appropriately managed Audit data now suggest a poor outcome such that many clinicians would now council against the use of adrenaline and other drugs to resuscitate extremely premature newborn babies
Adrenaline (epinephrine)In 2003 a Cochrane review of randomized controlled trials involv-ing adrenaline use for resuscitation of neonates was unable to identify a single clinical trial35 Despite the lack of human neo-natal data animal models show the potential of adrenaline in asphyxial cardiac arrest and it is reasonable to use it when ade-quate ventilation and chest compressions have failed to increase the heart rate above 60 beatsmin Use 10ndash30 μgkg intrave-nously and preferably via an umbilical venous line The tracheal route cannot be recommended but if used it is likely that doses within this range will be ineffective and 100 μgkg might be tried However the safety of such doses has not been studied
BicarbonateThe use of bicarbonate has long been controversial but many of the concerns relate to the rapid correction of acidosis in neonates after resuscitation or the routine use of bicarbonate infusion nei-ther of which can be advocated There are no published human neonatal data to support its use although some exist from animal studies Animal data have also shown that the binding of adren-aline to receptors in the myocardium is significantly impaired by lactic acidosis and recent work on human lymphocyte beta-adrenergic receptors supports this view Whether this is also true of the more important alpha receptors is unknown In practice reversing intracardiac acidosis may improve myocardial function and assist in achieving a return of spontaneous circulation 1ndash2 mmolkg of bicarbonate may be given but this remains a contro-versial area
VolumeVolume expansion should only be given when it is suspected that the baby has suffered blood loss or the infant appears to be in shock (pale poor perfusion weak pulse) and has not responded adequately to other resuscitative measures If there is no history suggestive of blood loss shock is most likely to be due to myo-cardial dysfunction in which case fluids should be administered cautiously The most logical replacement fluid would be blood but in its absence isotonic crystalloid rather than albumin is the solution of choice given in 10 mlkg aliquots and observing the response Three randomized trials in neonates have shown
9 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
isotonic crystalloid to be as effective as albumin for the treat-ment of hypotension but none has examined either the relative or actual effectiveness in resuscitation A recent blinded randomized study comparing normal saline albumin or no volume expansion in a normovolaemic asphyxiated neonatal animal model showed that volume expansion was not beneficial and made a number of parameters worse36
NaloxoneNaloxone is not recommended as part of the initial resuscita-tion of newborns with respiratory depression Before it is given supporting ventilation should have restored the heart rate and colour The dose is 100 μgkg intravenously or intramuscularly Tracheal administration cannot be recommended Although administration of naloxone to neonates who have been exposed to maternal opioids during labour is a practice of long-standing it lacks the proper evidence of efficacy
Non-response to resuscitation
There are few more frightening situations professionally than applying the correct interventions in resuscitating or stabilizing a baby and getting no response Each stage must be adequately performed before moving onto the next and this requires regular reassessment When experienced help is needed at a newborn resuscitation it is usually the airway and ventilation that require correction If the heart rate does not increase this usually means that the lungs have not been successfully aerated In some cases however it may mean that the heart cannot respond as the cir-culation is inadequate In this situation the only way to check that the lungs have been successfully aerated is to see the chest move with ventilation or to obtain evidence of ventilation from a detector of exhaled carbon dioxide If you do not see chest movement after another five breaths the most likely cause is an obstructed airway either due to incorrect positioning or because the jaw has not been drawn forwards An oropharyngeal airway can be very helpful at this point especially in the term baby Only very occasionally is the airway blocked by mucus vernix blood or meconium but if the airway is guaranteed and there is no heart rate response or chest movement this should be sought by direct suction of the trachea even in the absence of any meconium staining of liquor Pneumothoraces can occur spontaneously after delivery but are rare at resuscitation carried out with pressure-limited devices Equally rare are diaphragmatic hernias that have not been diagnosed antenatally giving problems at resuscitation
If the chest is moving but the heart rate has not responded to resuscitation consider rare possibilities such as fetal blood loss pneumothorax or heart block (mothers with undiagnosed systemic lupus erythematosis delivered for fetal bradycardia) as possibilities With adequate ventilation there is no evidence of oxygen concentrations less than 100 being responsible for prolonged bradycardia or failure to respond although current practice would support increasing the delivered oxygen concen-tration if resuscitation had been commenced using air
Outcome
The prognosis for the full-term baby subjected to sudden acute asphyxia is usually good provided the episode does not last for
paeDiatRiCS anD CHilD HealtH 184 17
long Most babies resuscitated from primary apnoea have no sequelae secondary to the resuscitation Many babies who start to breathe again regularly within 20 min of the circulation being restored recover completely but it is rare for a baby who is still gasping after 30 min to recover
The prognosis for the preterm baby of less than about 34 weeksrsquo gestation subjected to severe acute anoxia is less predict-able This is because of the risk of secondary intraventricular haemorrhage or periventricular intracerebral haemorrhage andor infarction after even a relatively brief asphyxial episode espe-cially in the period immediately around birth
The effects of chronic hypoxia are also difficult to predict but a reasonably clear idea of the extent of the problem should be obtainable within 36ndash48 h of the original chronic asphyxial insult A mild short-lasting state of hyperexcitability usually car-ries a good prognosis even if there is seizure activity but more severe symptoms can be associated with permanent handicap This is seen especially in infants with encephalopathy requiring ventilation
REFERENCEs
1 Biarent D Bingham R Richmond S et al european Resuscitation
Council guidelines for Resuscitation 2005 Section 6 paediatric life
support Resuscitation 2005 67(suppl 1) S97ndashS133
2 international liaison Committee on Resuscitation part 7 neonatal
resuscitation Resuscitation 2005 67 293ndash303
3 Singh J Santosh S Wyllie J mellon a effects of a course in
neonatal resuscitation - evaluation of an educational intervention
on the standard of neonatal resuscitation Resuscitation 2006 68
385ndash389
4 palme-Kilander C methods of resuscitation in low-apgar-score
newborn infants - a national survey Acta Paediatr 1992 81
739ndash744
5 Kroll l twohey l Daubeney p et al Risk factors at delivery and
the need for skilled resuscitation Eur J Obstet Gynecol Reprod Biol
1994 44 175ndash177
6 Wyllie Jp Resuscitation of the newborn The Foundation Years
2007 3(4) 153ndash157
7 Richmond S ed newborn life Support Resuscitation at Birth
london Resuscitation Council 2006
8 Ceriani Cernadas Jm Carroli g pelligrine l et al the effect of timing
of cord clamping on neonatal venous hematocrit values and clinical
outcome at term a randomized controlled trial Pediatrics 2006
117 e779ndashe786
9 mercer JS Vohr BR mcgrath mm padbury JF Wallach m oh W
Delayed cord clamping in very preterm infants reduces the incidence
of intraventricular hemorrhage and late-onset sepsis a randomized
controlled trial Pediatrics 2006 117 1235ndash1242
10 Dahm lS James lS newborn temperature and calculated heat loss
in the delivery room Pediatrics 1972 49 504ndash513
11 Stephenson J Du J tk o the effect of cooling on blood gas
tensions in newborn infants J Pediatr 1970 76 848ndash852
12 gandy gm adamsons Jr K Cunningham n Silverman Wa James lS
thermal environment and acid-base homeostasis in human infants
during the first few hours of life J Clin Invest 1964 43 751ndash758
13 gluck l Kulovich mV eidelman ai et al Biochemical development
of surface activity in mammalian lung pulmonary lecithin synthesis
0 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
in the human fetus and newborn and etiology of the respiratory
distress syndrome Pediatr Res 1972 6 81ndash99
14 Vohra S Roberts RS Zhang B Janes m Schmidt B Heat loss
prevention (Help) in the delivery room a randomised controlled
trial of polyethylene occlusive skin wrapping in very preterm infants
J Pediatr 2004 145 750ndash753
15 owen CJ Wyllie Jp Determination of heart rate in babies at birth
Resuscitation 2004 60 213ndash217
16 orsquoDonnell Cp Kamlin Co Davis pg Carlin JB morley CJ Clinical
assessment of infant colour at delivery Arch Dis Child Fetal
Neonatal Ed 2007 92 F465ndashF467
17 international liaison Committee on Resuscitation part 13 neonatal
Resuscitation guidelines Circulation 2005 112(suppl 24)
iV188ndashiV195
18 leone ta Rich W Finer nn neonatal intubation Success of
pediatric trainees J Pediatr 2005 146 638ndash641
19 orsquoDonnell Cp Kamlin Co Davis pg morley CJ endotracheal
intubation attempts during neonatal resuscitation success
rates duration and adverse effects Pediatrics 2006 117
e16ndash21
20 Repetto Je Donohue pa-CpK Baker SF Kelly l nogee lm use of
capnography in the delivery room for assessment of endotracheal
tube placement J Perinatol 2001 21 284ndash287
21 gandini D Brimacombe JR neonatal resuscitation with laryngeal
mask airway in normal and low birth weight infants Anesth Analg
1999 89 642ndash643
22 esmail n Saleh m ali a laryngeal mask airway versus endotracheal
intubation for apgar score improvement in neonatal resuscitation
Egypt J Anesthiol 2002 18 115ndash121
23 Wiswell te gannon Cm Jacob J et al Delivery room management
of the apparently vigorous meconium-stained neonate results of
the multicenter international collaborative trial Pediatrics 2000
105 1ndash7
24 Vain ne Szyld eg prudent lm Wisewell te aguilar am Vivas ni
oropharyngeal and nasopharyngeal suctioning of meconium-stained
neonates before delivery of their shoulders multicentre randomised
controlled trial Lancet 2004 364 597ndash602
25 Bjorklund lJ ingimarsson J Curstedt t larsson a Robertson B
Werner o lung recruitment at birth does not improve lung function
in immature lambs receiving surfactant Acta Anaes Scand 2001 45
986ndash993
26 Bjorklund lJ ingimarsson J Curstedt t et al manual ventilation
with a few large breaths at birth compromises the therapeutic effect
of subsequent surfactant replacement in immature lambs Pediatr
Res 1997 42 348ndash355
paeDiatRiCS anD CHilD HealtH 184 17
27 taskar V John J evander e Robertson B Jonson B Surfactant
dysfunction makes lungs vulnerable to repetitive collapse and re-
expansion Am J Respir Crit Care Med 1997 155 313ndash320
28 muscedere Jg mullen JB gan K Slutsky aS tidal ventilation at low
airway pressures can augment lung injury Am J Respir Crit Care Med
1994 149 1327ndash1334
29 nilsson R grossman g Robertson B Bronchiolar epithelial lesions
induced in the premature rabbit neonate by short periods of artificial
ventilation Acta Pathol Microbiol Scand 1980 88 359ndash367
30 probyn me Hooper SB Dargaville pa et al positive end expiratory
pressure during resuscitation of premature lambs rapidly improves
blood gases without adversely affecting arterial pressure Pediatr
Res 2004 56 198ndash204
31 Wood Fe morley CJ Dawson Ja et al improved techniques
reduce face mask leak during simulated neonatal resuscitation
study 2 Arch Dis Child Fetal Neonatal Ed in press doi101136
adc2007117788
32 tan a Schulz a orsquoDonnell CpF Davis pg air versus oxygen for
resuscitation of infants at birth Cochrane Database Syst Rev 2004
(3) CD002273
33 Davis pg tan a orsquoDonnell Cp Schulze a Resuscitation of newborn
infants with 100 oxygen or air a systematic review and meta-
analysis Lancet 2004 364 1329ndash1333
34 Dawes g Fetal and neonatal physiology Chicago year Book
publisher 1968 p 141ndash159
35 Ziino aJa Davies mW Davis pg epinephrine for the resuscitation
of apparently stillborn or extremely bradycardic newborn infants
Cochrane Database Syst Rev 2003 (2) CD003849
36 Wyckoff m garcia D margraf l perlman J laptook a Randomized
trial of volume infusion during resuscitation of asphyxiated neonatal
piglets Pediatr Res 2007 61 415ndash420
Practice points
bull Resuscitation at birth is different from that at all other times
of life
bull a standard approach can be applied to most newborn
resuscitation
bull guidelines are based on a rigorous evaluation of evidence
where possible
bull evidence is sparse but evolving
bull most preterm babies require stabilization rather than
resuscitation
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Acidndashbase physiology and blood gas interpretation in the neonateSusern tan
morag Campbell
Abstractacidndashbase balance describes the complex processes that work to main-
tain a stable extracellular pH for optimal cellular function the process
of balancing the production and neutralization of tissue acid provides a
great challenge for newborn infants who have significantly higher rates
of acid production than adults Factors which help maintain a stable
acidndashbase balance include buffers the respiratory system and renal sys-
tem Both intracellular and extracellular buffers resist changes in pH
the most important extracellular buffer system for maintaining stable
pH is the bicarbonate system in response to acidosis or alkalosis the
respiratory system balances the production of acid with the clearance
of Co2 by altering respiratory rate the kidneys provide a delayed but
sustained response to pH imbalance by excreting either acidic or alkaline
urine in response to systemic acidosis and alkalosis respectively in sick
premature infants these systems have a limited capacity completely to
control pH this review discusses the physiology of the three systems
which control acidndashbase balance patterns of clinical abnormalities in
acidndashbase status and their underlying causes are discussed We present
a systematic approach to blood gas analysis and interpretation in new-
born infants
Keywords acidosis alkalosis bicarbonate bloodndashgas analysis
metabolic pH
Introduction
Blood gas analysis is a routine procedure performed on newborn babies receiving respiratory support in the neonatal intensive care The combination of invasive and non-invasive assessment of ventilation and oxygenation enables clinicians appropriately to modify respiratory care according to each individual babyrsquos rapidly changing clinical status
Understanding the fundamentals of acidndashbase balance helps us to use blood gas analysis not only to assess respiratory sta-tus but also to provide information on metabolic status and the adequacy of tissue perfusion
Susern Tan MBBS MRCP is Clinical Fellow at the Neonatal Intensive Care
Unit 6th Floor North Wing St Thomasrsquo Hospital London SE1 7EH UK
Morag Campbell MBChB MRCP is Consultant Neonatologist at the
Neonatal Intensive Care Unit 6th Floor North Wing St Thomasrsquo
Hospital London SE1 7EH UK
paeDiatRiCS anD CHilD HealtH 184 17
What is understood by acid-base balance
Acidndashbase balance refers to the complex physiological processes used by the body to maintain a stable extracellular pH1 A serum pH within the range of 735ndash745 provides the ideal environment for cellular metabolism Maintaining a stable pH is critical as the metabolic activity of proteins is pH dependent and small changes in hydrogen ion (H+) concentration can potentially alter physio-logical function
Acids are substances that yield free H+ in solution while a base accepts H+ and in solution combines with an acid to neu-tralize it In the normal metabolic state H+ are continuously pro-duced and neutralized to maintain a steady pH balance12 The rate of H+ production is two to three times higher in neonates because of their rapid growth rates and increased acid production from protein turnover and bone mineralization The challenge of maintaining a stable pH through processing and neutralizing H+ is therefore greatest in newborn infants
Using exact values of H+ concentration to assess acidndashbase status is cumbersome and it is more commonly expressed as pH defined by the equation
pH = minuslog H+
Maintaining acidndashbase balance
The balance between production and excretion of acids in the body is controlled by buffer systems which have an immediate effect and by the respiratory and the renal systems
Buffer systemsBuffer solutions resist change in pH when acid or alkali is added due to their capacity to absorb or give up H+ The three main buffer systems in the body are the bicarbonate phosphate and protein systems1ndash3 The protein and phosphate buffer systems are intracellular and act as lsquosinksrsquo for extracellular H+ which are exchanged with intracellular potassium (K+) and sodium ions (Na+) In an acute metabolic acidosis hyperkalaemia may develop due to this H+ exchange4
The bicarbonate buffer system is extracellular and consists of a mixture of carbonic acid (H2CO3) and sodium bicarbon-ate (NaHCO3) This buffer system helps maintain a stable pH by soaking up excess H+ with HCO3
minus which in solution forms carbonic acid (H2CO3) Carbonic acid is a weak acid and readily dissociates to give CO2 which is transported in dissolved form to the lungs for excretion
H+ + HCO3minus harr H2CO3 harr H2O + CO2
The bicarbonate system therefore completes the neutraliza-tion of excess H+ and a stable plasma pH is maintained The relationships between pH HCO3
minus and CO2 in this system are described by the HendersonndashHasselbalch equation15
pH = 61 + log HCO3minus003 times CO2
where 61 is the log of the dissociation coefficient of carbonic acid and 003 the solubility of CO2 in plasma Buffers are most potent when there are equal amounts of H+ and HCO3
minus in solution The
2 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
bicarbonate system is not a potent buffer however as HCO3minus
and CO2 are readily altered by the body this system plays a very powerful role in pH homeostasis15
Respiratory regulationThe respiratory system adapts within minutes to hours as part of the acute response to acidosis This system modifies pH by balancing production of H+ with ventilatory clearance of CO2
H+ directly stimulates chemoreceptors in the respiratory cen-tre of the brainstem producing an increase in respiratory rate26 The response to respiratory acidosis is very rapid as CO2 easily diffuses across the bloodndashbrain barrier however in metabolic acidosis compensation is delayed until plasma bicarbonate fully equilibrates with cerebrospinal fluid (CSF) bicarbonate There is an inverse relationship between alveolar ventilation and partial pressure of dissolved carbon dioxide (PaCO2) a reduction in alveolar ventilation raises PaCO2 and decreases pH Changes in pH therefore affect alveolar ventilation and conversely changes in alveolar ventilation cause significant changes in pH
Renal regulationThe kidneys provide a delayed but sustained response to acidndashbase imbalances by excreting either acidic or alkaline urine In full-term and preterm babies the capacity for acid excretion and bicarbonate reabsorption is reduced as glomerular filtration rates are low and tubular function immature7 Renal function matures with gestation postnatal age and glucocorticoid and thyroid hormones78 Due to their limited capacity to preserve HCO3
minus newborn infants have lower serum bicarbonate levels and are predisposed to acidosis7
Bicarbonate is not effectively reabsorbed due to its size and electrical charge Instead intraluminal HCO3
minus combines with secreted H+ in tubular luminal fluid to produce carbonic acid which dissociates to give H2O and CO2 This CO2 diffuses into tubular cells combines with intracellular H2O and forms carbonic acid which liberates HCO3
minus and H+ HCO3minus is then
recovered to the circulation by exchange for chloride ions (Clminus) through the basal cell membrane247
Renal acid secretion occurs at all sites except the loop of Henle Primary active transport accounts for 5 and secondary for the remaining 95 of total H+ excretion Secondary trans-port involves an exchange between luminal Na+ and intracel-lular H+ Both ions bind to a membrane transport protein The Na+ concentration gradient between the tubular lumen and cells enables Na+ drag into the cell which generates energy to fuel active H+ excretion into the tubular lumen1ndash47
Quantifying acidosis
Standard base excess is a calculated value derived from PaCO2 and pH It is expressed as the mmollitre of base above or below normal buffer bases required to correct the pH to 74 at a PaCO2 of 40 mmHg A negative base excess or base deficit indicates an acidosis while a positive base excess indicates a relative alkalosis15
Anion gap is the measured difference between anions and cations in the blood
Anion gap = (Na+ + k+) minus (HCO3+Clminus)
paeDiatRiCS anD CHilD HealtH 184 17
Calculation of the anion gap enables clinicians better to define the underlying cause of a metabolic acidosis9 The common causes of an increased anion gap acidosis in neonates include lactic acidosis due to tissue hypoperfusion and hypoxia it may also be seen with certain inborn errors of metabolism and in uraemia910 The anion gap can help distinguish between the rela-tively benign non-anion gap hyperchloraemic acidosis seen in premature infants and a pathological lactic acidosis due to poor end-organ perfusion1011
Strong ion theory
Stewart described a complex acidndashbase model which proposed that H+ concentration results from the dissociation of water which is influenced by PaCO2 the strong ion difference and plasma weak acids12
Strong ions are ions that dissociate at normal body pH and include Na+ K+ and Clminus Weak acids in plasma which contrib-ute include albumin inorganic phosphate and plasma proteins their concentrations do not change with pH and are therefore a constant The effect of these factors and other unmeasured tissue ions on acidndashbase status can be quantified by the calculation of the strong ion gap (SIG)112 In the neonatal unit it is perhaps more important that we consider how principles of this model may relate to acidndashbase status rather than fully to quantify the SIG Theoretically low albumin and phosphate levels which fre-quently occur in premature infants by reducing the concentra-tion of weak acids can produce a relative alkalosis while high phosphate levels in renal failure may contribute to acidosis
Tissue oxygenation
Oxygenation is closely linked to acidndashbase status as optimal cel-lular function requires oxygen to fuel aerobic metabolism and produce energy In hypoxic conditions anaerobic metabolism predominates which is energy inefficient and results in a lactic acidosis1011
Tissue oxygen availability is related to regional blood flow haemoglobin level and haemoglobin oxygen affinity Arterial blood gases measure the partial pressure of dissolved oxygen (PaO2) which represents a small component of total oxygen con-tent the majority being transported bound to haemoglobin The relationship between percentage haemoglobin saturation (SaO2) and PaO2 is described by the sigmoidal oxyhaemoglobin disso-ciation curve which enables us to relate the two measures to each other235 The affinity of haemoglobin for oxygen is altered by local tissue factors Increases in temperature H+ PaCO2 and 23-diphosphoglycerate (DPG) levels shift the oxyhaemoglobin dissociation curve to the right reducing affinity for oxygen Decreases in temperature H+ PaCO2 and 23-DPG levels shift the curve to the left increasing oxygen affinity1ndash35 In the body haemoglobin oxygen affinity continuously changes increasing in the lungs to enable efficient oxygen uptake and decreasing at tissue level to provide efficient oxygen delivery to metabolically active tissues
Avoiding both hypoxia and hyperoxia is important in the neo-natal unit as deleterious effects of hypoxia are seen in infants with pulmonary hypertension1314 while hyperoxia is associated with an increased incidence of retinopathy of prematurity1516
3 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Clinical acidndashbase imbalances
Clinical acidndashbase imbalances can be respiratory metabolic or a mixture of both These abnormalities may be corrected by the acidndashbase regulatory mechanisms in the body in an attempt to maintain normal pH (Figure 1)
Respiratory acidosisThis occurs when any disorder leads to decreased alveolar ventilation Common causes of respiratory acidosis are listed in Table 1 Reduced respiratory clearance of CO2 means more dissolved CO2 accumulates in the plasma leading to increased production of carbonic acid and H+ Through chemoreceptor stimulation respiratory acidosis rapidly alters ventilation in an attempt to reduce CO226 Chemoreceptor mediated ventila-tory increases may only partly adjust in premature infants with underlying lung disease In babies with a sustained respiratory acidosis eg in chronic lung disease then metabolic compen-sation occurs through increased renal excretion of H+ and reabsorption of HCO3
minus slowly restoring pH to around 80 of normal47
paeDiatRiCS anD CHilD HealtH 184 17
The management of PaCO2 levels in infants receiving mechan-ical ventilation has important clinical implications Premature babies have impaired cerebral autoregulation17 and adverse neurological sequelae are reported in association with high PaCO2 levels18ndash20 Ventilation strategies which advocate lsquoper-missive hypercarbiarsquo have been developed to minimize airways damage from mechanical ventilation21 Published data suggest pulmonary benefits however the safe level of PaCO2 remains to be defined in premature infants2021
Respiratory alkalosisThis occurs when more CO2 is excreted than is produced by the body Pathological conditions leading to respiratory alkalosis are rare Hyperventilation in the neonatal setting is often iatrogenic or may be due to disorders in brainstem control of breathing including hypoxicndashischaemic encephalopathy or primary central nervous system abnormalities (see Table 1)
If respiratory alkalosis is sustained it may be compensated for by reduced reabsorption of filtered bicarbonate Reported adverse associations of low PaCO2 include periventricular leuco-malacia and intraventricular haemorrhage1922
K+
H+
Overventilation
CO2 + H2O harr H2CO3 harr H+ + HCO3ndash
Bicarbonate Buffer
Intracellular Buffer
uarr H+ excretionuarr HCO3
ndash absorption
uarr buffered H+
(NH4+ H2PO4
ndash)uarr ventilation rate
RespiratoryAcidosis
MetabolicAcidosis
darr CO2and uarr pH
RespiratoryAlkalosis
MetabolicAlkalosis
darr H+ anduarr pH
darr ventilation rate
uarrCO2
and darr pH
darr H+ excretiondarr HCO3
ndash absorption
uarrH+ and
darr pH
Brain
Brain
Intracellular Buffer
H+
K+
Sepsis
HypoxiaRDS
Metabolismand growth
Diuretics
Airwayobstruction
Neuromuscularproblems
IEM
Gastric losses
+ +
ndash -
Renal BufferRespiratory Buffer
Figure 1 mechanisms for regulation of extracellular pH iem inborn errors of metabolism RDS respiratory distress syndrome
4 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Common causes of acidndashbase imbalances
pH PCO2 H2CO3 Base excess Common neonatal causes
Respiratory acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
uarr normal normal bull upper airway obstruction choanal atresia
pierre-Robin sequence
bull lung abnormalities respiratory distress
syndrome transient tachypneoa of
newborn pneumonia meconium aspiration
syndrome pulmonary hypoplasia
congenital pulmonary malformations
bull Central hypoventilation hypoxic-ischaemic
encephalopathy intracranial haemorrhage
bull neuromuscular insufficiency congenital
myopathies congenital neuropathies
bull iatrogenic inadequate ventilatory settings
Compensated lower limit
of normal
uarr uarr gt+3
metabolic acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
normal darr ltminus3 increased anion gap
bull lactic acidosis sepsis hypoperfusion
shock necrotizing enterocolitis
bull inorganic acidosis inborn errors of
metabolism renal failure
normal anion gap
bull increased gastrointestinal H2Co3 losses
ileostomy diarrhoea
bull Renal tubular acidoses
Compensated lower limit
of normal
darr darr ltminus3
Respiratory alkalosis Uncompensated gt 745 darr normal normal bull iatrogenic excessive ventilatory settings
bull Compensatory hyperventilation hypoxic-
ischaemic encephalopathy
Compensated higher limit
of normal
darr darr ltminus3
metabolic alkalosis Uncompensated gt 745 normal uarr gt+3 bull gastric losses vomiting non-replacement
of excessive nasogastric aspirates
bull thiazide and loop diuretics
bull Hypokalaemia
Compensated higher limit
of normal
uarr uarr gt+3
Table 1
Metabolic acidosisThis frequently affects infants in the neonatal unit and has many causes1011 (see Table 1) There may be overproduction of tissue acid impaired acid clearance gastrointestinal loss of bicarbonate or an exogenous increased acid load eg chloride total paren-teral nutrition (TPN) or albumin1ndash323
Calculation of the anion gap to distinguish an increased anion gap acidosis from a non-anion gap acidosis is important both for treatment and prognosis1011 Acidosis stimulates respiratory compensation but this is limited in unstable infants Similarly renal compensation with improved HCO3
minus conservation is con-strained by tubular immaturity Treatment of the acidosis should be directed at the underlying cause eg hypoxia hypotension or excess Clminus rather than by administration of base
Metabolic alkalosisThis is unusual in neonates and is most frequently seen in infants with chronic lung disease or heart failure who are receiving diuretics Diuretics cause alkalosis by increasing renal fluid and Na+ losses An active process to reabsorb Na+ occurs in tubule cells which through enhanced H+ secretion and HCO3
minus reab-sorption produce alkalosis27
paeDiatRiCS anD CHilD HealtH 184 17
Metabolic alkalosis may also occur with excessive loss of gas-tric contents eg protracted vomiting or inadequate replacement of nasogastric aspirates (see Table 1)
Interpreting blood gases
Blood gas measurements can provide important diagnostic and prognostic information and a systematic approach to blood gas analysis is described in Table 2 The clinical management of infants with abnormal gases requires a good understanding of acidndashbase physiology and tissue oxygenation and an apprecia-tion of factors which may affect the reliability of samples
Arterial blood sampling is the gold standard however indwelling arterial catheters and arterial stab samples are usually restricted to infants who are critically ill or those who require sig-nificant ongoing intervention Gases are most frequently measured in capillary or venous samples which correlate well with arterial samples for PaCO2 pH and base excess in babies and children receiving intensive care These correlations however are not valid in infants with peripheral vasoconstriction and hypotension2324
Non-invasive monitoring techniques may enable us to reduce the frequency of blood gas sampling Transcutaneous monitoring
5 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
A systematic approach to blood gas analysis
1 Collect the relevant information
bull type of gas ndash capillary or arterial
bull Current respiratory support ndash document level
bull transcutaneous Co2 and Sao2 levels
bull Clarify no significant clinical events before sampling
2 pH accept a range between 730 and 745 in newborn
babies this is lower than in older children is there an
alkalosis (pH gt 745) or an acidosis (lt 730)
3 Co2 aim for a range between 45 and 65 kpa a paCo2 level
more than 65 kpa suggests inadequate alveolar ventilation
while less than 45 kpa suggests hyperventilation Correlate
values with non-invasive measures
4 o2 Can only be assessed from arterial gases aim for pao2
between 60 and 80 kpa Correlate results with pulse
oximetry levels
5 HCo3 and base excess normal HCo3 level is between 20 and
24 mmollitre and bases excess +3 to minus3
6 anion gap look at the anion gap and lactate to help identify
the cause of an acidosis normal lactate levels should be less
than 2 mmollitre
7 Respiratory or metabolic compensation look at the pH and
assess whether it is appropriate for the Co2 level or is there
evidence of compensation
8 interpret use both the clinical history and blood gas
findings to help you identify the primary problem aim your
management at treating the underlying cause
9 Reassess if clinical management changes have been made
repeat the blood gas after an appropriate time interval to
ensure improvement
Table 2
provides a highly accurate and reliable method for measuring PaCO2 through the skin it can however be technically difficult may cause tissue damage and is of limited reliability when peripheral perfusion is reduced25 Continuous end-tidal CO2 measurements correlate well with arterial CO2 values in patients with normal ventilation and perfusion however in babies with lung disease alveolar collapse small tidal volumes and rapid respiratory rates can make these measurements unreliable26 Despite its limitations transcutaneous monitoring provides the best method for CO2 trend monitoring in the neonatal intensive care unit (NICU)25
Oxygen saturation levels can be continuously measured non-invasively using pulse oximetry While oximetry is easy to perform and accurate on occasion SaO2 levels obtained may be unreliable when tissue perfusion is poor or with movement artefact SaO2 monitoring is highly sensitive at detecting hypoxia but is limited in detecting hyperoxia as at levels more than 90 small changes in SaO2 may result in unacceptably large increases in PaO227 It is therefore essential that SaO2 alarm limits are set for all neonates receiving respiratory support to detect hypoxia and prevent hyperoxia1627
Continuous non-invasive monitoring provides invaluable information when managing complex infants in the NICU but it does not replace the need for regular blood gas analysis
paeDiatRiCS anD CHilD HealtH 184 17
ReFeRenCeS
1 Kellum Ja Determinants of blood pH in health and disease
Crit Care 2000 4 6ndash14
2 Quigley R Baum m neonatal acid base balance and disturbances
Semin Perinatol 2004 28 97ndash102
3 Brouillette Rt Waxman DH evaluation of the newbornrsquos blood gas
status Clin Chem 1997 43 215ndash221
4 Chan JC acid-base disorders and the kidney Adv Pediatr 1983 30
401ndash471
5 Siggaard-andersen o the pH-log pCo2 blood acidndashbase nomogram
revised Scand J Lab Invest 1962 14 598ndash604
6 Saetta m mortola Jp interaction of hypoxic and hypercapnic stimuli
on breathing pattern in the newborn rat J Appl Physiol 1987 62
506ndash512
7 Baum m Quigley R postnatal renal development in Seldin DW
giebisch g eds the kidney physiology and pathophysiology new
york lippincott Williams and Wilkins 2000 p 703ndash726
8 ortiz la Quan a Weinberg a et al effect of prenatal
dexamethasone on rat renal development Kidney Int 2001 59
1663ndash1669
9 gabow pa Kaehny WD Fennessey pV goodman Si gross pa
Schrier RW Diagnostic importance of an increased serum anion gap
N Engl J Med 1980 303 854ndash858
10 lorenz Jm Kleinman li markarian K oliver m Fernandez J Serum
anion gap in the differential diagnosis of metabolic acidosis in
critically ill newborns J Pediatr 1999 135 751ndash755
11 Deshpande Sa platt mp association between blood lactate and
acid-base status and mortality in ventilated babies Arch Dis Child
1997 76 F15ndash20
12 Stewart pa modern quantitative acid-base chemistry Can J Physiol
Pharmacol 1983 61 1444ndash1461
13 Dakshinamurti S pathophysiologic mechanisms of persistent
pulmonary hypertension of the newborn Pediatr Pulmonol 2005
39 492ndash503
14 mourani pm ivy DD gao D abman SH pulmonary vascular
effects of inhaled nitric oxide and oxygen tension in
bronchopulmonary dysplasia Am J Respir Crit Care Med 2004
170 1006ndash1013
15 Deulofeut R Critz a adams-Chapman i Sola a avoiding hyperoxia
in infants le 1250 g is associated with improved short- and long-
term outcomes J Perinatol 2006 26 700ndash705
16 Chow lC Wright KW Sola a Can changes in clinical practice
decrease the incidence of severe retinopathy of prematurity in very
low birth weight infants Pediatrics 2003 111 339ndash345
17 Boylan gB young K panerai RB Rennie Jm evans DH Dynamic
cerebral autoregulation in sick newborn infants Pediatr Res 2000
48 12ndash17
18 Kaiser JR gauss CH pont mm Williams DK Hypercapnia during
the first 3 days of life is associated with severe intraventricular
hemorrhage in very low birth weight infants J Perinatol 2006 26
279ndash285
19 Fabres J Carlo Wa phillips V Howard g ambalavanan n Both
extremes of arterial carbon dioxide pressure and the magnitude of
fluctuations in arterial carbon dioxide pressure are associated with
severe intraventricular hemorrhage in preterm infants Pediatrics
2007 119 299ndash305
20 thome uH Carroll W Wu tJ et al outcome of extremely preterm
infants randomized at birth to different paCo2 targets during the
first seven days of life Biol Neonate 2006 90 218ndash225
6 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
21 Carlo Wa Stark aR Wright ll et al minimal ventilation to prevent
bronchopulmonary dysplasia in extremely-low-birth-weight infants
J Pediatr 2002 141 370ndash374
22 okumura a Hayakawa F Kato t et al Hypocarbia in preterm
infants with periventricular leukomalacia the relation between
hypocarbia and mechanical ventilation Pediatrics 2001 107
469ndash475
23 peters o Ryan S matthew l Cheng K lunn J Randomised
controlled trial of acetate in preterm neonates receiving parenteral
nutrition Arch Dis Child 1997 77 F12ndash15
24 yildizda D yapiciolu H yilmaz Hl Sertdemir y Correlation of
simultaneously obtained capillary venous and arterial blood gases
of patients in a paediatric intensive care unit Arch Dis Child 2004
89 176ndash180
25 aliwalas ll noble l nesbitt K et al agreement of carbon
dioxide levels measured by arterial transcutaneous and end tidal
methods in preterm infants 28 weeks gestation J Perinatol 2005
25 26ndash29
26 Hagerty JJ Kleinman me Zurakowski D et al accuracy of a new
low-flow sidestream capnography technology in newborns a pilot
study J Perinatol 2002 22 219ndash225
paeDiatRiCS anD CHilD HealtH 184 17
27 poets CF Wilken m Seidenberg J Southall Dp von der Hardt H
Reliability of a pulse oximeter in the detection of hyperoxemia
J Pediatr 1993 122 87ndash90
Practice points
bull a stable extracellular pH is important for optimal cellular
functioning
bull abnormalities in acidndashbase balance are regulated by buffer
systems and the respiratory and renal tract
bull maintaining a stable pH is challenging for newborn babies
due to their high rates of acid production and immature
regulatory mechanisms
bull arterial or capillary blood gases provide an effective way to
monitor acidndashbase balance in newborns
bull Blood gases should be analysed in a structured manner
assessing pH and then respiratory and metabolic components
bull the treatment of acidndashbase abnormalities should be directed
at the underlying problem not merely at correcting pH
7 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Recognition and management of neonatal seizuresmalcolm levene
AbstractSeizures are the most common major manifestation of central nervous
system dysfunction in the newborn there are many causes but perina-
tal asphyxia and haemorrhagicinfarction lesions account for about 75
there is now considerable evidence that frequent but short seizures in
the neonate affect subsequent neurodevelopmental outcome Studies
using eeg or modified continuous tracing of eeg activity (aeeg or CFm)
have shown that there is often electroconvulsive dissociation this re-
fers to poor correlation between electrical seizures and clinical seizures
Commonly used anticonvulsants appear to increase electroconvulsive
dissociation effective management of neonatal seizures has proved very
disappointing and less than 50 of seizures are abolished by first-line
anticonvulsant medication (phenobarbitone or phenytoin) Drugs such
as midazolam and lidocaine may further reduce seizures but require
more evaluation the challenge is to assess new and more effective anti-
convulsants which are themselves associated with little neurotoxicity
Keywords antiepileptic drugs eeg neonatal seizures neurodegeneration
Convulsions are the most common major neurological sign seen in newborn infants and their incidence estimated from large population studies is 26 per 1000 live births1 Premature infants are over four times more likely to have convulsions than full-term infants12 Neonatal status epilepticus (continuous seizure activity lasting 30 min or more) diagnosed clinically is rare and accounts for only 5 of infants with seizures1 although this is now recognized more frequently as the result of continuous EEG monitoring3
Neonatal convulsions are described as presenting in a num-ber of different ways and various seizure types can be seen in the same baby over a number of hours The frequencies of the various patterns of seizure activity are given in Table 1 In very premature babies and to a lesser extent in term infants minor movement abnormalities may be difficult to identify as subtle seizures These include lip smacking tongue thrusting mouth-ing pedalling type movements of the lower limbs or swimming movements of the arms Apnoea can be a common manifesta-tion of subtle seizures The signs can be protean and vary from baby to baby or even in the same baby Virtually any stereotypic
Malcolm Levene MD FMedSc FRCPCH FRCH is Professor and Head of
Department of Paediatrics and Child Health at University of Leeds Leeds
and Honorary Neonatologist at Leeds General Infirmary Leeds UK
paeDiatRiCS anD CHilD HealtH 184 178
movement may be a manifestation of a seizure disorder in the newborn
Aetiology
The more carefully the fitting baby is investigated the more likely it is that a cause for the seizures will be found A number of recent papers have described the aetiology of neonatal con-vulsions after extensive investigations14 Tekgul et al4 recently studied a consecutive group of full-term infants with evidence of neonatal convulsions (recognized both clinically and on EEG) and reported their outcome Table 2 summarizes these data as well as risk of moderate or severe disability for each causative factor Perinatal asphyxia is the commonest cause for convul-sions in term infants with haemorrhagic or ischaemic lesions also being common
Overall the prognosis for the group of term babies with con-vulsions was good 72 had a favourable outcome Where asphyxia (hypoxicndashischaemic insult) is the cause of neonatal convulsions the outcome is poor in 50 The prognosis for neonatal convulsions when they were due to arterial or cere-brovenous infarction or intracranial haemorrhage was generally good Individually inborn errors are a very rare cause of neo-natal convulsions but in view of the treatable nature of some of these it is essential that these be considered and investigated appropriately5
Patterns of seizure activity in the newborn
Movement pattern Frequency ()
Clonic 50
tonic 20
Subtle 10ndash35 depending on maturity
myoclonic 5
Table 1
Cause incidence and outcome of neonatal convulsions in term infants14
Aetiological factor Incidence () Poor outcome ()
asphyxia 38ndash40 50
Cerebral arteriovenous
infarction
20 0
intracranial haemorrhage 12ndash20 13
Congenital cerebral anomaly 5ndash10 100
Hypoglycaemiahypocalcaemia 3ndash19
infection 3ndash20
inborn error of metabolism 1
unknown cause 10ndash13 0
Refers to moderate and severe neurodevelopmental abnormalitynumbers too small to make meaningful predictions
Table 2
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Controversies in the clinical management of neonatal seizures
In recent years we have learnt much more about the neurobi-ology of seizures and their effect on the developing brain The neonatal brain is in a neurophysiologically hyperexcitable state compared to the more mature brain and therefore is more prone to seizure activity This is due largely to a relative excess of GABA neuroreceptors GABA receptors are usually inhibitory but in the immature brain they have a paradoxically excitatory effect This changes at about term in primates and with progressive develop-ment they adopt a neuroinhibitory role6
The propensity to seizures in the neonatal brain makes resolv-ing the balance of risks between continuing seizure activity on the one hand against potentially adverse effects of therapy on the other a very important equation Added to this is the problem of accurately diagnosing neonatal seizures and whether commonly used anticonvulsants are successful in controlling them
These conundrums can be posed as a series of challenging questions which are discussed below
Do neonatal convulsions cause brain injuryConvulsions are a sign of neurological compromise and may indi-cate significant underlying structural brain damage or biochemi-cal disturbance which may cause further brain damage in its own right There has been considerable debate about the scale of the disability that convulsions cause the immature brain over and above that due to the underlying cause Most of our knowledge comes from studies in rodents and these have provided some tentative answers to this question
Seizures in the mature brain lead to neuronal necrosis but studies in very young rat pups whose brain development is somewhat similar to full-term infants have shown that a series of five brief seizures on five successive days does not cause struc-tural neuronal damage but does produce morphological changes in hippocampal neurones and worryingly deficits in the rat learning and visual spatial memory function in adolescent and adult life7 A single prolonged neonatal convulsion in similarly immature rats does not produce any functional effects8 Others have shown that following priming of the neonatal rat brain by short seizures as described above a further insult comprising induction of status epilepticus in the same rats at an older age causes neuronal necrosis9 This has been referred to as the lsquotwo hit hypothesisrsquo10
A more specific question is does seizure activity in an already significantly compromised brain cause additional neuropathol-ogy Wirrell et al11 studied a series of immature rat pups with the induction of an hypoxicndashischaemic (asphyxial) insult fol-lowed by either chemically-induced fits or a control sham pro-cedure In the more severely asphyxiated animals the degree of brain damage was increased significantly in those that had the additional burden of induced seizures
In summary these studies show that the immature brain is more resistant to short frequent post-seizure damage than the mature brain but despite resulting in no loss of neuronal numbers the function of the brain is permanently affected in later life In the asphyxiated brain seizures appear to have an additional adverse effect on brain damage Furthermore the immature brain that has been lsquoprimedrsquo by early seizures is more
paeDiatRiCS anD CHilD HealtH 184 179
vulnerable to status epilepticus later in life It would appear from these data that frequent seizures in the human infant should be stopped and this begs the question as to whether currently used anticonvulsants effectively control neonatal seizures
Can we rely on clinical versus EEG diagnosis of neonatal convulsionsTraditionally the diagnosis of neonatal convulsions has been made by observation and description of the frequency of abnor-mal movements EEG has been technically difficult in the hostile electrical activity of a neonatal intensive care environment and considerable expertise is required for analysis of the trace It is usually not practical to undertake traditional EEG recordings at the time the baby shows abnormal movements More recently various technological developments have allowed more direct investigation of neuronal electrical activity by either video-EEG or compressed recording of the amplitude integrated EEG (aEEG or CFM)
Rennie et al3 at Kingrsquos College Hospital London have under-taken extensive evaluation of video-EEG and have found that this technique detects many convulsions not recognized by a single channel aEEG or CFM trace Of 19 infants with evidence of convulsions on EEG only four were recognized on CFM but this may have been due to the observersrsquo lack of experi-ence with this technique In other centres that have developed appropriate expertise aEEG or CFM has proved more sensitive to the detection of seizures Video-EEG studies have also shown that many movements interpreted by experienced clinicians to be seizures are not associated with abnormal cortical activity Conversely many electrical seizures are not associated with abnormal movements This is referred to as electroconvulsive dissociation
In summary clinical observation alone to detect the fitting baby is unreliable in that it may either over-detect seizure activ-ity which is not present on EEG or under-detect clinical seizures in infants with EEG-proven convulsions The decision as to which babies to treat with antiepileptic drugs therefore becomes somewhat arbitrary
Do anticonvulsants stop neonatal seizuresAlthough neonatal seizures are common there are few random-ized controlled trials assessing the benefits of antiepileptic drugs (AEDs) in the treatment of this condition Phenobarbitone is the most widely used first-line AED and in an Australasian study 95 of neonatologists and paediatric neurologists used this drug as first-line management12 The most commonly used loading dosage is 20 mgkg but regimens of up to 40 mgkg have been recommended (Table 3)13 Four trials have evaluated the effect of phenobarbitone in abolishing neonatal seizures Two of these studies used EEG to monitor response to the drug1415 and one compared phenobarbitone with phenytoin15 In the latter study seizures were completely controlled in only 43 of babies and in the group where phenytoin was the first drug used com-plete seizure control was achieved in 45 This study switched babies from their first AED to the other if complete control was not obtained on EEG monitoring after exposure to first-line therapy In babies who had been given phenobarbitone as first-line therapy seizure control was only achieved in 57 after phenytoin was added In those given phenytoin first complete
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Dosage regimens for first- second- and third-line anticonvulsants in the neonatal period
Loading dose Second loading dose if first
unsuccessfulMaintenance dose
phenobarbitone 20 mgkg by slow iv injection 10 mgkg iv 25ndash5 mgkg od
phenytoin 20 mgkg iv over 20 min not recommended
midazolam 150ndash200 μgkg iv infusion 1 μgkgmin iv infusion increasing to 5 μgkgmin
until favourable response
lidocaine 2 mgkg iv over 10 min 6 mgkgh for 6 h iv then 4 mgkgh for 12 h then
2 mgkgh for 12 h
lorazepam 005ndash01 mgkg by slow iv injection
Diazepam 03ndash04 mgkg iv over 3ndash5 min
lidocaine should not be used if the infant has previously been treated with phenytoin
Table 3
seizure control was achieved with the adding of phenobarbitone in 62
Boylan et al14 assessed the efficacy of phenobarbitone (20ndash40 mgkg iv over 20 min) in 14 babies monitored by video-EEG in only four was there complete abolition of seizures and in the other 10 electroconvulsive seizure activity increased whereas clinical evidence of seizures reduced This has been termed elec-troclinical dissociation and anticonvulsant drug use in the new-born appears to increase this feature They also showed that the babies least likely to respond to the first-line AED are those with the most abnormal background EEG
Two studies have evaluated the use of phenobarbitone in babies who had sustained significant asphyxial insult at birth Hall et al13 compared high-dose phenobarbitone (mean 39 mgkg) versus standard dose (27 mgkg) and reported fewer convul-sions and a significant reduction of severe disability or death in the high dose group (RR 030 CI 010ndash093) A recent study from India16 of babies with hypoxicndashischaemic encephalopathy ran-domized 25 babies to phenobarbitone (20 mgkg loading dose) and compared them with 20 control babies Only 2 of 25 (4) in the phenobarbitone group developed convulsions compared with 8 of 20 (40) in the control group (p = 001) Because of the specific enrolment criteria (asphyxial insult) neither of these studies is strictly comparable to the studies by Painter et al15 and Boylan et al14 whose intention was to assess the efficacy of first-line anticonvulsant therapy on convulsions of any cause diagnosed either clinically or by EEG
Other anticonvulsants used as second- and third-line drugs have been subject to few studies in the newborn Midazolam is administered as a bolus followed by continuous infusion A recent study17 has shown that in 10 of 13 neonates given intravenous midazolam for status epilepticus control of electri-cal seizures was achieved within the first hour of treatment having been previously shown to be refractory to phenobarbi-tone treatment Some of these babies required a second bolus infusion of midazolam to obtain control of all electrographic seizures
In some parts of Europe lidocaine is used as a third-line anti-convulsant Malingre et al18 evaluated 20 infants refractory to
paeDiatRiCS anD CHilD HealtH 184 180
both phenobarbitone and midazolam and who were then given lidocaine by continuous infusion Lidocaine was effective in abolishing electroconvulsive seizures diagnosed by aEEG in 76 of the treatment courses studied No babies developed cardiac arrhythmias a previously reported complication of lidocaine in older patients As a result of pharmacokinetic studies the dosage regimen has been modified (see Table 3)
In summary phenobarbitone is effective in seizure control in less than 50 of babies and even when combined with phe-nytoin the efficacy of these drugs together remains poor More worrying is the observation that phenobarbitone tends to reduce clinically evident seizures thereby giving the clinician a false sense of security whilst having little or no effect on the num-bers of electroconvulsive disorders This has been summarized appropriately as lsquoafter all these years we still love what doesnrsquot workrsquo19 Both midazolam and lidocaine infusions appear to be effective in abolishing severe seizures in some infants resistant to phenobarbitone Lidocaine should not be given to babies previ-ously exposed to phenytoin for fear of a synergistic adverse effect on cardiac rhythm
Do antiepileptic drugs cause brain damageA riskndashbenefit analysis is needed to evaluate the efficacy of anticonvulsants in stopping neonatal seizures which is poor with standard anticonvulsants as discussed above against the risk of administering the anticonvulsant drugs themselves Phenobarbitone has been reported to have adverse effects on the developing brain including inhibition of brain growth20 neuronal toxicity21 and adverse behavioural and cognitive effects into adult life when administered to young animals22 Phenytoin shows unpredictable plasma levels and potential cardiotoxicity
Recent studies have shown an effect of AED exposure on the developing brain by causing neurodegeneration23 Phenytoin administration to immature rat pups at doses which produce serum levels similar to those achieved in human neonates was associated with widespread neuronal death as a result of apop-tosis (programmed cell death) Phenobarbitone had a similar effect when a dosage regimen similar to 40 mgkg was used and
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
this effect was maximal in the more immature brain Diazepam and clonazepam also resulted in a similar effect Midazolam and lidocaine were not tested in this study The combination of phenobarbitone or phenytoin with diazepam had a particularly profound effect on neurodegeneration
In summary recent data suggest that the commonly used AEDs for neonatal convulsions may in themselves cause neuro-degeneration due to apoptosis with lasting effects on develop-ment Many babies with neonatal convulsions are treated with at least two AEDs and this may produce more severe adverse effects than the seizures themselves
Practical management of neonatal seizures
Assimilation of these data and formulation of a rational policy is difficult when faced with a fitting neonate on an intensive care unit and pressure on the medical staff to lsquodo somethingrsquo but it is important to accept that sometimes doing nothing is preferable to using potentially dangerous drugs in a situation which does not warrant such intervention Many babies who have normal interseizure neurological clinical findings and whose seizures are relatively brief and infrequent probably do not need anticon-vulsant medication A normal or near-normal background EEG trace should reassure the clinician that anticonvulsants can be withheld
Some causes of neonatal convulsions are treatable such as meningitis hypoglycaemia hypocalcaemia and inborn errors of metabolism and each baby should be rapidly and carefully investigated for cause of the convulsions
In some babies clinical assessment of seizures is difficult ie when the baby is very sick small or paralyzed Sometimes it may be difficult to assess the significance of certain movement pat-terns Under these circumstances an EEG may prove to be very helpful In many units EEG is not available out of hours and a simple aEEG or CFM is strongly advised Modern instruments are very simple to apply and prolonged or frequent seizures should be identified with only moderate training The printout can be faxed to a more senior doctor if there is doubt as to what is shown on the trace
The balance of knowledge now is that frequent seizures cause additional damage to the developing brain and that treatment to abolish the seizures is warranted Unfortunately there is little evidence that the majority of seizures can be effectively termi-nated by current standard therapy Furthermore it appears that the more abnormal the background EEG the more difficult it is to control the seizures Nevertheless a written protocol for the management of neonatal convulsions is required on each unit Phenobarbitone and phenytoin remain the mainstay of treat-ment although their effectiveness is disappointing There is little to suggest that midazolam is more effective than lidocaine as third-line therapy but lidocaine is precluded if phenytoin has been previously used
In view of the anxiety as to the neurodegenerative effects on the immature brain of most anticonvulsants used in the neonatal period (particularly when multiple drugs are used) it is prefer-able to use only one drug to maximum dosage before introduc-ing a second In addition the duration of anticonvulsants should be minimized and the drugs stopped at the earliest opportu-nity It is my practice to stop anticonvulsants prior to discharge
paeDiatRiCS anD CHilD HealtH 184 18
from hospital if the baby is neurologically normal on clinical examination
REFEREnCES
1 Ronen gm penney S andrews W the epidemiology of clinical
neonatal seizures in newfoundland a population-based study
J Pediatr 1999 134 71ndash75
2 lanska mJ lanska DJ Baumann RJ et al a population-based study
of neonatal seizures in Fayette County Kentucky Neurology 1995
45 724ndash732
3 Rennie Jm Chorley g Boylan gB et al non-expert use of the
cerebral function monitor for neonatal seizure detection Arch Dis
Child Fetal Neonatal Ed 2004 89 F37ndashF40
4 tekgul H gauvreau K Soul J et al the current etoliologic profile
and neurodevelopmental outcome of seizures in term newborn
infants Pediatrics 2006 117 1270ndash1280
5 Surtees R Wolf n treatable neonatal epilepsy Arch Dis Child 2007
92 659ndash661
6 Ben-ari y Holmes gl effects of seizures on developmental
processes in the immature brain Lancet Neurol 2006 5 1055ndash
1063
7 Holmes gl gairsa Jl Chevassus-au-louis n et al Consequences of
neonatal seizures in the rat morphological and behavioral effects
Ann Neurol 1998 44 845ndash857
8 Stafstrom Ce Chronopoulos a thurber S et al age-dependent
cognitive and behavioural deficits following kainic-acid inducing
seizures Epilepsia 1993 34 420ndash432
9 Schmid R tandon p Stafstrom Ce et al effects of neonatal seizures
on subsequent seizure-induced brain injury Neurology 1999 53
1754ndash1761
10 Hoffmann aF Zhao Q Holmes gl Cognitive impairment following
status epilepticus and recurrent seizures during early development
support for the ldquotwo-hit hypothesisrdquo Epilepsy Behav 2004 5
873ndash877
11 Wirrell eC armstrong ea osman lD et al prolonged seizures
exacerbate perinatal hypoxic-ischemic brain damage Pediatr Res
2001 50 445ndash454
12 Carmo KB Barr p Drug treatment of neonatal seizures by
neonatologists and paediatric neurologists J Paediatr Child Health
2005 41 313ndash316
13 Hall Rt Hall FK Daily DK High-dose phenobarbital therapy in term
newborn infants with severe perinatal asphyxia a randomized
prospective study with three-year follow-up J Pediatr 1998 132
345ndash348
14 Boylan gB Rennie Jm pressler Rm et al phenobarbitone neonatal
seizures and video-eeg Arch Dis Child Fetal Neonatal Ed 2002 86
F165ndash170
15 painter mJ Scher mS Stein aD et al phenobarbital compared with
phenytoin for the treatment of neonatal seizures N Engl J Med
1999 341 485ndash489
16 Singh D Kumar p narang a a randomized controlled trial of
phenobarbital in neonates with hypoxic ischemic encephalopathy
J Matern Fetal Neonatal Med 2005 18 391ndash395
17 Castro Conde JR Borges H Domenech martinez e et al midazolam
in neonatal seizures with no response to phenobarbital Neurology
2005 64 876ndash879
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
18 malingre mm Van Rooij lgm Rademaker Cma et al Development
of an optimal lidocaine infusion strategy for neonatal seizures Eur
J Pediatr 2006 165 598ndash604
19 Sankar R painter mJ neonatal seizures after all these years we still
love what doesnrsquot work Neurology 2005 64 776ndash777
20 Diaz J Schain J Bailey Bg phenobarbital-induced brain growth
retardation in artificially reared rat pups Biol Neonate 1977 32 77ndash82
21 mattson RH phenobarbital toxicity in levy RH Dreifuss Fe
mattson RH et al eds antiepipeptic Drugs 3rd edn new york
Raven 1985 p 341ndash355
22 mikati ma Holmes gl Chronopoulos a et al phenobarbital
modifies seizure-related brain injury in the developing brain Ann
Neurol 1994 36 425ndash453
23 Bittigau p Sifringer m genz K et al antiepileptic drugs and
apoptotic neurodegeneration in the developing brain Proc Natl
Acad Sci U S A 2002 99 15089ndash15094
paeDiatRiCS anD CHilD HealtH 184 182
Practice points
bull the clinician needs to be aware that almost any repetitive
stereotype movement pattern can be a manifestation of
neonatal seizures
bull eeg is important in defining neonatal seizures
bull Frequent short-lived seizures have been shown to cause long-
term neurodevelopmental problems
bull Conventional anticonvulsant medication is ineffective in
abolishing neonatal seizures in greater than 50 of cases
bull there is evidence that exposure of the neonatal brain to
multiple anticonvulsants causes neuronal death
bull Future research is needed to evaluate more effective
anticonvulsants for treating this condition
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
Emotional support for families of sick neonatesMarina nicolaou
cristine Glazebrook
AbstractParents of sick neonates experience high levels of stress anxiety and
depression Most interventions with families of sick infants have focused
on fostering the motherndashinfant relationship through the provision of
information about infant developmental needs or through increased
motherndashinfant contact Many of these studies have reported improved
maternal well-being though there are some concerns about the scope
and practicality of large-scale interventions The few studies to have
prioritized emotional support for parents of sick neonates have pro-
duced encouraging results even interventions requiring relatively few re-
sources such as telephone support parent-to-parent support and group
support have been associated with reduced psychological morbidity for
parents The needs of parents can change throughout their infantrsquos hos-
pitalization and not all want or benefit from the provision of additional
support Thus neonatal intensive care units should aim to provide a
varied flexible and sustainable programme of support options Further
research should focus on the needs of fathers
Keywords mental health neonatal intensive care parents
The admission of an infant to neonatal care is acknowledged to be a source of considerable distress for families This review aims to explore evidence for the psychological impact on families of having an infant in neonatal intensive care and to identify evi-dence for the effectiveness of interventions to promote parental well-being It will conclude with recommendations for strategies to support parents of vulnerable infants and suggestions for fur-ther research
Psychological impact of neonatal care for parents
The majority of research examining the effect on parents of having a sick neonate has focused on families of premature or low birthweight infants Such research has found that parents with a sick neonate exhibit high levels of stress compared to normative samples and to parents of healthy full-term infants1 Singer et al2 examined the stress experienced by mothers of high-risk very low birthweight (VLBW) low-risk VLBW and term
Marina Nicolaou MPhil is a Teaching Assistant at the School of
Community Health Sciences University of Nottingham Nottingham UK
Cristine Glazebrook PhD is a Professor of Health Psychology at the School
of Community Health Sciences University of Nottingham Nottingham UK
PaeDiaTrics anD cHilD HealTH 184 196
infants Several self-report measures were used including the Brief Symptom Inventory the Parenting Stress Index (PSI) the Impact on Family Scale and the Family Inventory of Life Events and Changes (FILE) Mothers of VLBW infants had more psycho-logical distress at 1 month compared to mothers of term infants Mothers of high-risk VLBW infants also reported high psycho-logical distress at 2 years and high levels of parenting stress at 3 years Mothers have also been found to have higher stress levels compared to fathers Shaw et al3 examined the prevalence of acute stress disorder (ASD) in 40 parents whose infants were in the neonatal intensive care unit (NICU) Nearly half of the moth-ers (44) met the criteria for ASD although none of the fathers did Furthermore the severity of the symptoms (measured by the number of concurrent symptoms) was greater for the moth-ers than for the fathers3 The reasons behind this difference have been widely speculated with some believing that it is due to the mothersrsquo greater psychological involvement with the infant as evidenced by their general greater vulnerability to postpartum psychological disorder It could also reflect gender differences in coping style
Having an infant who requires intensive medical care repre-sents a significant emotional burden for families Not only is there extreme anxiety surrounding the infantrsquos health and distress for the childrsquos suffering there is also the unfamiliar and intimidating environment of the NICU to adjust to Hopper in her review of the literature identified sources of stress for parents of sick neo-nates as falling into three areas4 Situational factors included the severity of the infantrsquos illness and how parents adapted to the life crisis of having a sick infant Personal factors involved parental emotions about their roles and the instrumental and informa-tional support which were available to them The third area was classified as environmental sources of stress and included the environment of the NICU and the relationship between parents and members of staff This relationship has been examined by several studies in the nursing literature nurses are seen as ide-ally placed to provide the necessary support and information to parents with sick neonates However whilst some studies have shown that supportive and helpful hospital staff can have a posi-tive effect on parents other studies have highlighted the prob-lems and difficulties which can manifest It has been shown that parents and nurses often have very different ideas about issues eg the necessary skills and competencies needed in an NICU or the characteristics that make a lsquogood motherrsquo
Research has shown that there may be a relationship between high levels of parental stress and an increased likelihood of depression5 Postpartum depression is a psychiatric illness which appears in 10ndash15 of postpartum women Its reported preva-lence rates however have ranged from less than 10 up to 306 depending on the instruments used the population exam-ined and the timing of the research Several factors have been found to be associated with postpartum depression including poor social support and infant-related stressors6 Evidence indi-cates that postnatal depression may be underreported and this is of concern since the mental and psychological health of the mother can affect her relationship with her infant and thus the infantrsquos cognitive and emotional development5 Depressed moth-ers appear to look touch and talk to their infants less frequently and also appear to show fewer positive and more negative faces7 The vocalizations of mothers suffering with depression have also
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
been found to be less effective at promoting cognitive growth and learning in infants8
If researchers are interested in finding ways of providing sup-port for families of sick neonates then they must listen to what such families perceive their needs to be in order to avoid increas-ing anxiety and distress Furthermore the provision of appropri-ate support be it emotional informational or social will enhance parental coping abilities increase self-esteem and reduce anxiety It should be noted though that the research conducted around these issues has often taken lsquosupport needsrsquo as being synony-mous with lsquoinformation needsrsquo Such studies have examined the type the amount and quality of information that parents receive and perceive themselves as needing but have not explored in equal depth the perceived emotional support needs of families who have a sick infant In addition the needs of parents may change throughout their infantrsquos illness Ward examined the per-ceived needs of 52 parents of infants in an NICU9 Parents rated the needs of their hospitalized infant as most important along with the need to be reassured Interestingly they ranked their support needs as least important This research was conducted during the first week of the infantsrsquo hospitalization however which would explain the preoccupation of the parents with the infantrsquos health These results demonstrate that if researchers want to find ways of providing emotional support to parents of sick neonates they must be prepared not only to listen to parents but also to be flexible enough to satisfy the parentsrsquo changing needs and expectations
Interventions aimed at supporting parents
Most interventions that been evaluated in controlled studies have focused on supporting the motherndashinfant relationship and provid-ing information on infant development Many of these interven-tions have included the aim of improving the parental emotional state and thus psychological outcomes such as stress or anxi-ety have been assessed However few studies appear to include fathers This means that strategies implemented to provide emo-tional support to families of sick neonates are often derived from interventions tailored for mothers even though fathers may have different emotional needs
A wide range of interventions with mothers and infants has been evaluated in the NICU Increasing motherndashinfant contact through kangaroo care has been found to reduce maternal anxiety1011 and educational programmes delivered to fami-lies in the NICU have also been associated with reduced emo-tional difficulties in parents12ndash14 Kaaresen and colleagues implemented an intervention which consisted of eight sessions before discharge and four home visits all by trained nurses The sample included 71 premature infants in the intervention group 69 premature infants in the control group and 74 infants in the full-term control group The randomized controlled trial found that the intervention reduced parenting stress in both mothers and fathers of premature infants compared to controls to a level equivalent to parents in the term control group13 At 6 months corrected age mothers of preterm infants who had not received the intervention had total PSI scores which were 17 points higher than the mothers of infants born at term (an effect size of 057) A similar study evaluated the efficacy of an educationalndashbehavioural programmendashCreating Opportunities for
PaeDiaTrics anD cHilD HealTH 184 19
Parent Empowerment (COPE) ndash through a randomized controlled trial with 260 families of premature infants14 COPE was a four-phase educationalndashbehavioural programme which began as early as 2ndash4 d after mothers had given birth and continued until 1 week after discharge from the NICU The programme consisted of audiotaped and written infant behaviour information along with photographs which focused on common behaviours and characteristics of premature infants It also included various par-ent activities in the form of a four-phase workbook which aimed to assist mothers in the implementation of the experimental infor-mation COPE was found significantly to reduce maternal stress in the NICU as well as maternal anxiety and depressive symptoms after hospitalization In contrast a cluster randomized trial of a parenting intervention delivered to mothers of very premature infants from soon after birth showed no benefits for parenting stress1 The authors hypothesized that the intervention had not been of sufficient intensity particularly in the weeks surrounding discharge Neonatal care presents a significant barrier to parent-ing in the early weeks following a very preterm birth and so inter-ventions which focus on the developmental needs of infants and the parentndashchild relationship should particularly aim to support parents as they take on the parenting role There was also concern that the intervention had failed to reach those most at risk
Since large-scale projects can be costly to implement and may often fail to reach the families in most need it may be wiser to focus on intervention programmes which are more practical and easier to implement within a neonatal care setting Research has shown that even interventions which are based on one-off meet-ings with parents of sick neonates can be effective Jotzo and Poets examined the effect of an intervention programme aimed at reducing the severity of traumatic responses as a result of giv-ing birth prematurely15 Their programme consisted of a one-off intervention meeting along with additional psychological help throughout the hospitalization of the infant The meeting cov-ered a variety of issues including a reconstruction of the events shortly before and after the infantrsquos birth relaxation techniques discussion of coping strategies available resources and social support and support during emotional outbursts The measures used included the Impact of Event Scale (IES) and the Peritrau-matic Dissociative Experience Questionnaire At discharge the mothers who received the intervention were found to have a significantly lower traumatic impact as a result of premature birth Furthermore fewer mothers in the intervention group showed symptoms of clinically significant psychological trauma at discharge compared to mothers in the control group (36 vs 76)15 The lsquoParents Circle Programrsquo is another intervention with a similar structure16 This consisted of a 90 min session for parents with the aim of enhancing the developing relationship between parents and infants and to offer parents support A total of 104 parents (59 mothers and 45 fathers) and 44 members of hospital staff were asked to evaluate the programme and their results were analysed using content analysis Families reported gaining perspective on their situation feeling supported becom-ing aware of cues and optimizing interactions and becoming aware of available resources Parents and staff alike felt that participating in the intervention helped parents overcome the difficulties associated with the early time of their infantrsquos hos-pitalization Additional studies have also found positive results with fairly minimal interventions including discussion groups
7 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
in the NICU music during kangaroo care and pairing mothers of sick neonates with trained mothers who had been through similar experiences
Parent support programmes
Parent support programmes (PSPs) which are based in NICUs can provide parents with the opportunity to talk to parents who have been in similar situations and also to discuss their emo-tions with professionals who can help them cope with their situa-tion111718 The parent-to-parent support programme for mothers of preterm infants evaluated by Preyde and Ardal included edu-cational parental support group meetings and individual par-ent-to-parent support (primarily telephone support)19 Measures used included the Parental Stressor Scale NICU the State and the Trait Anxiety Inventories and the Beck Depression Inven-tory After 4 months of participation mothers in the intervention group reported lower levels of stress state anxiety and depres-sion compared to control group mothers The authors speculated however that the participants who were able to meet face to face with other parents were those who benefited the most Hurst conducted a comprehensive survey of an NICU-based PSP This PSP was provided in a variety of formats including a weekly parent support group hospital visitation and 24-h telephone sup-port20 Of the 477 participants 303 families used the PSP dur-ing a 2-year evaluation period with 78 using only one form of support and 18 using two forms Of a sub-sample of 48 parents asked to complete an evaluation of the PSP 92 stated that they would recommend such a programme to other parents Furthermore the majority of parents felt that it made them feel supported and helped them deal with their emotions20 This is an indication that such programmes can be very successful in sup-porting parents throughout their infantrsquos hospitalization It also shows that it can be beneficial to give parents several options and formats when it comes to such support services It is impor-tant to consider though that both the Hurst and the Preyde and Ardal studies found that some participants did not find the sup-port programmes helpful even reporting that they had caused them increased stress and anxiety Therefore it should not be assumed that support programmes will suit every individual and will provide the required support for all parents1920 NICUs need to be flexible enough to provide parents with a range of forms of support to choose from
The increased understanding of the strains that parents of sick neonates have to deal with has also led to efforts to improve customary practices in NICUs Family-centred care focuses on infants and their needs and attempts to redefine the relationship between parents and caregivers These practices strive to provide parents with support during their infantrsquos illness by focusing on freely sharing information and on the collaboration between parents and hospital staff Family-centred care has been found to be associated with several beneficial outcomes including improved parental satisfaction increased parental comfort staff satisfaction and decreased parental stress18 Research is already examining these practices and questioning how these can be improved further Such research reflects the increasing effort focused on lsquohumanizingrsquo the environment in NICUs in order to make parents feel more comfortable about spending time with their infants
PaeDiaTrics anD cHilD HealTH 184 19
Conclusion
Surprisingly few interventions have prioritized the provision of emotional support for parents of sick neonates or accounted for the changing needs and wishes of parents over the course of their infantrsquos care Large-scale supportive education-based inter-ventions have been shown to be effective in reducing parental distress However the feasibility and sustainability of such pro-grammes should also be considered Programmes which require significant additional resources can be expensive and there are also issues of training and quality control Interventions which require significant input from parents may also place additional burdens on families making them potentially less accessible to those most at risk Arguably the aim should be to explore ways of providing acceptable and effective informational support which could be complemented by emotional support from health professionals and from other parents in the unit Increasingly studies are exploring the use of computers and multimedia as an engaging flexible and cost-effective method of targeting indi-vidual needs and providing support and information Such com-puter-based and interactive multimedia interventions have been found to be successful with a range of patient groups and could therefore be examined as a complementary method of providing informational support to families with sick neonates
REfEREnCEs
1 Glazebrook c Marlow n israel c et al randomised trial of a
parenting intervention during neonatal intensive care Arch Dis Child
Fetal Neonatal Ed 2007 92 F438ndash443
2 singer lT salvator a Guo s collin M lilien l Baley J Maternal
psychological distress and parenting stress after the birth of a very
low-birth-weight infant JAMA 1999 281 799ndash805
3 shaw rJ Deblois T ikuta l Ginzburg K Fleisher B Koopman c
acute stress disorder among parents of infants in the neonatal
intensive care nursery Psychosomatics 2006 47 206ndash212
4 Hopper a sources of stress for parents of a sick neonate a
literature review Pediatr Nurs 2000 30 29ndash32
5 Davis l edwards H Mohay H wollin J The impact of very
premature birth on the psychological health of mothers Early Hum
Dev 2003 73 61ndash70
6 Bernazzani O saucier J-F David H Borgeat F Psychosocial
predictors of depressive symptomatology level in postpartum
women J Affect Disord 1997 46 39ndash49
7 Field T infants of depressed mothers Infant Behav Dev 1995 18
1ndash13
8 Kaplan Ps Bachorowski J-a Zarlengo-strouse P child-directed
speech produced by mothers with symptoms of depression fails
to promote associative learning in 4-month-old infants Child Dev
1999 70 560ndash570
9 ward K Perceived needs of parents of critically ill infants in
a neonatal intensive care unit (nicU) Pediatr Nurs 2001 27
281ndash286
10 lai Hl chen cJ Peng Tc et al randomized controlled trial of music
during kangaroo care on maternal state anxiety and preterm infantsrsquo
responses Int J Nurs Stud 2006 43 139ndash146
8 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
11 Tallandini Ma scalembra c Kangaroo mother care and mother-
premature infant dyadic interaction Infant Ment Health J 2006 27
251ndash275
12 Ohgi s Fukuda M akiyama T Gima H effect of an early intervention
programme on low birthweight infants with cerebral injuries
J Paediatr Child Health 2004 40 689ndash695
13 Kaaresen Pi ronning Ja Ulvund se Dahl lB a randomized
controlled trial of the effectiveness of an early-intervention program
in reducing parenting stress after preterm birth Pediatrics 2006
118 e9ndash19
14 Melnyk BM Feinstein nF alpert-Gillis l et al reducing premature
infantsrsquo length of stay and improving parentsrsquo mental health
outcomes with the creating opportunities for parent empowerment
(cOPe) neonatal intensive care unit program a randomized
controlled trial Pediatrics 2006 118 e1414ndash1427
15 Jotzo M Poets cF Helping parents cope with the trauma of
premature birth an evaluation of a trauma-preventive psychological
intervention Pediatrics 2005 115 915ndash919
16 Pearson J andersen K evaluation of a program to promote positive
parenting in the neonatal intensive care unit Neonatal Netw 2001
20 43ndash48
17 roman l lindsay J Boger r et al Parent-to-parent support
initiated in the neonatal intensive care unit Res Nurs Health 1995
18 385ndash394
18 Meyer ec coll cTG lester BM Boukydis cFZ McDonough sM Oh w
Family-based intervention improves maternal psychological well-
being and feeding interaction of preterm infants Pediatrics 1994
93 241ndash246
PaeDiaTrics anD cHilD HealTH 184 19
19 Preyde M ardal F effectiveness of a parent ldquobuddyrdquo program for
mothers of very preterm infants in a neonatal intensive care unit
CMAJ 2003 168 969ndash973
20 Hurst i One size does not fit all Parentsrsquo evaluations of a support
program in a newborn intensive care nursery J Perinat Neonatal
Nurs 2006 20 252ndash261
Practice points
bull Parents of sick neonates experience significant distress and
exhibit higher levels of stress anxiety and depression than
parents of healthy infants
bull educational support emotional support and increased
motherndashinfant contact have been shown to promote maternal
well-being
bull emotional support for fathers has been largely neglected in
the research literature
bull Parents benefit from a choice of supportive facilities which
could include face-to-face sessions with health professionals
telephone support hospital visitation parent-to-parent
support and unit-based group support meetings
bull Parentsrsquo support needs can change during their infantrsquos
hospitalization and not all parents want or benefit from the
provision of additional information and emotional support in
the neonatal unit
9 copy 2008 elsevier ltd all rights reserved
Personal Practice
When should enteral feeds be started in preterm infantsnicholas D embleton
AbstractPaediatricians are regularly faced with the question of when best to start
enteral feeds in preterm infants this is important as longer term out-
come may be compromised by sub-optimal nutrition in early life clinical
factors that may affect the decision to start and the risk and benefits
are discussed
Keywords breast milk feeding nutrition parenteral nutrition
Key points in the history
Alice is lsquonutritionally vulnerablersquo and whilst this may not be immediately apparent it will affect her long term outcome Her energy stores are extremely limited and consist primarily of pro-tein She has less than 5 fat and little energy associated with stored glycogen She is losing about 1 gkgd protein equivalent so she needs at least that and a minimum of 50ndash60 kcalkg of energy just to maintain the status quo let alone grow
Her weight is on the 25th centile Review of any antenatal his-tory may reveal whether fetal growth was normal Fetal growth retardation can occur with a weight greater than 10th centile The presence of antenatal absent or reversed end diastolic flow in the umbilical artery indicates poor gut blood flow This increases the risk of necrotizing enterocolitis (NEC) and might suggest a more cautious approach to starting feeds1
She has no important cardiovascular problems but if she were hypotensive gut blood flow may be low There is no umbilical
Nicholas D Embleton BSC (Hons) MBBS (Hons) MD FRCPCH is Consultant in
Neonatal Medicine at Newcastle Neonatal Service Royal Victoria
Infirmary Newcastle upon Tyne NE1 4LP UK
Should you start feeds at a day of age
alice was born following spontaneous labour at 30 weeksrsquo
gestation she weighed 1300 g and is now 18 h old she was
briefly ventilated and then extubated to continuous positive
airway pressure 12 h ago in 35 oxygen she has had caffeine
citrate but still has intermittent episodes of self-correcting
apnoea she was commenced on iv 10 dextrose but this was
replaced by a parenteral amino acid solution (referred to as
lsquotPnrsquo) along with intralipid at 0900 this morning serum glucose
is 11 mmoll and blood pressure is 42 systolic
PaeDiatrics anD cHilD HealtH 184 20
arterial catheter in situ but there is no good evidence that this should delay the decision to start feeds Her glucose is high but this is quite common in a baby like this Could this be a sign of sepsis Caffeine does not affect the incidence of NEC2 The great-est risk factor for NEC in this case is prematurity
What else might be found on examination
Up until 24 h ago she was swallowing large amounts of amniotic fluid What will have changed since then
General examination should confirm peripheral perfusion lsquogestaltrsquo view (does she look lsquowellrsquo) and cardiovascular status lsquoBowel soundsrsquo are not usually helpful
The most important variable likely to affect gut perfusion is the arterial duct Precordial lsquoheaversquo and a loud murmur are sug-gestive but it is possible to have a significant ductal shunt in a baby with a normal examination Cardiac ultrasound will con-firm this diagnosis It might be better to treat a large shunt first with indometacin and to delay starting feeds for a further 24 h
It is not possible to assess gut perfusion clinically but normal perfusion elsewhere (adequate urine output usually indicates adequate renal perfusion) would be reassuring Most preterm babies have a few abdominal lsquoloopsrsquo visible but a distended abdomen with many palpable loops suggests ileus This might be secondary to sepsis or poor gut blood flow Preterm babies do not pass much meconium in the first 24ndash48 h
Balance of risks between starting and withholding feeds
Alice requires 35ndash4 gkgd of protein and 120 kcalkgd to grow3 This will initially be provided parenterally Delaying feeds increases the risk of gut villous atrophy and prolongs the need for lsquototal parenteral nutrition (TPN)rsquo TPN requires intravenous access and so increases the risk of sepsis and when prolonged use is required combined with the lack of enteral feeding may result in hepatic impairment
Delaying feeds may allow a gut that has been chronically under-perfused to re-establish more normal perfusion although normal gut endocrine function digestive enzyme upregulation and motility require a source of intraluminal nutrients1 A recent study suggested benefit from delaying the introduction of feeds4 but methodologi-cal problems exist5 Although a Cochrane meta-analysis suggested no benefit only two studies were included6 A large UK-based trial is examining the effect of early or late feeding in preterm infants who were born growth retarded following identification of antena-tal absent or reversed end diastolic flow in the umbilical artery7
When starting feeds what volume should be used
There are no good data to guide this decision We start with 24 mlkg (1 mlkgh) and then increase by this amount each day Most babies achieve full enteral feeds (ge150 mlkgd) by a week of age Feeding guidelines improve the outcome8 Measure-ment or assessment of gastric aspirates is not consistently useful in predicting subsequent feeding intolerance or development of NEC Aspirate volumes equivalent to or sometimes greater than the amount given in the preceding 1ndash2 h are usually normal Most aspirates have a greenish colour Thick bloody or intensely bile-stained aspirates require detailed assessment
0 copy 2008 elsevier ltd all rights reserved
Personal Practice
What else affects decisions and outcome
Feeding success is affected by sepsis and NEC Scrupulous atten-tion should be paid to hand washing and intravenous access and blood sampling should be minimized There is no good evidence to support the routine use of pro-kinetic agents or H2 blockers
The most important clinical intervention affecting the occur-rence of NEC is the use of breast milk9 All efforts should be directed at persuading parents of the benefits and supporting the process Some clinicians delay starting feeds for a further 24 h whilst expressed breast milk becomes available Donor breast milk might be equally efficacious10
RefeRenceS
1 Dorling J Kempley s leaf a Feeding growth restricted preterm
infants with abnormal antenatal Doppler results Arch Dis Child Fetal
Neonatal Ed 2005 90 F359ndash363
2 schmidt B roberts rs Davis P et al caffeine therapy for apnea of
prematurity N Engl J Med 2006 354 2112ndash2121
PaeDiatrics anD cHilD HealtH 184 20
3 embleton nD Pang n cooke rJ Postnatal malnutrition and growth
retardation an inevitable consequence of current recommendations
in preterm infants Pediatrics 2001 107 270ndash273
4 Berseth cl Bisquera Ja Paje VU Prolonging small feeding volumes
early in life decreases the incidence of necrotizing enterocolitis in
very low birth weight infants Pediatrics 2003 111 529ndash534
5 Menon G Boyle eM embleton nD et al introduction of enteral
feeds in preterm infants Pediatrics 2004 114 327ndash328
6 Kennedy Ka tyson Je chamnanvanikij s early versus delayed
initiation of progressive enteral feedings for parenterally fed low
birth weight or preterm infants Cochrane Database Syst Rev 2000
cD001970
7 wwwnpeuoxacukadept
8 Patole sK de Klerk n impact of standardised feeding regimens on
incidence of neonatal necrotising enterocolitis a systematic review
and meta-analysis of observational studies Arch Dis Child Fetal
Neonatal Ed 2005 90 F147ndash151
9 lucas a cole tJ Breast milk and neonatal necrotising enterocolitis
Lancet 1990 336 1519ndash1523
10 Boyd ca Quigley Ma Brocklehurst P Donor breast milk versus
infant formula for preterm infants systematic review and meta-
analysis Arch Dis Child Fetal Neonatal Ed 2007 92 F169ndash175
1 copy 2008 elsevier ltd all rights reserved
self-assessment
Case 1A term male infant born to consanguineous parents is assessed at 24 h of age due to poor feeding profuse yellow watery diar-rhoea and irritability He weighed 32 kg at birth and delivery was uneventful There was no polyhydramnios He has been breastfed since birth On examination he is pale with a non-tender but distended abdomen and reduced bowel sounds His weight is 275 kg and he looks dehydrated Examination is otherwise normal
Initial investigations (normal values in parentheses) showed
sodium 149 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 65 mmollitre (25ndash75)
creatinine 147 μmollitre (40ndash110)
chloride 119 mmollitre (95ndash105)
haemoglobin 172 gdl (140ndash200)
White blood cell count 80 times 109litre (100ndash260)
Platelet count 302 times 109litre (150ndash400)
arterial blood gas
ph 720 (730ndash745)
PcO2 23 kPa (46ndash60)
Bicarbonate 68 mmollitre (220ndash260)
Base excess minus186 mmollitre (minus20 to +20)
lactate 59 mmollitre (06ndash24)
An abdominal X-ray shows distended bowel loops with no intramural thickening or pneumoperitoneum (Figure 1)
He was given nil by mouth and received intravenous fluids and antibiotics His dehydration improved but the metabolic acidosis and diarrhoea persisted despite receiving no enteral feeds and the commencement of total parenteral nutrition Blood and stool cultures were negative
1 Which of the following best describes these results Choose ONE answer ONLY from the followingA Hypernatraemia hyperchloraemic metabolic acidosis
with increased anion gapB Hypernatraemia hyperchloraemic metabolic acidosis
with normal anion gap
Manish Sadarangani BM BCh MA MRCPCH is Clinical Research Fellow
at the Department of Paediatrics University of Oxford Centre for
Clinical Vaccinology and Tropical Medicine Churchill Hospital
Oxford OX3 7LJ UK
Shabna Rajapaksa MB BChir MA MRCPCH is Specialist Registrar in
Paediatrics at the Paediatric Intensive Care Unit John Radcliffe
Hospital Oxford OX3 9DU UK
Nicholas Mann MD FRCP FRCPCH DCH is Consultant Paediatrician at the
Department of Paediatrics Royal Berkshire Hospital Reading RG1
5AN UK
self-assessment
C Hypernatraemic dehydration and compensated metabolic acidosis
D Acute renal failureE Renal tubular acidosis
2 What is the likely diagnosis Choose ONE answer ONLY from the followingA Hirschsprung disease ndash long segmentB Cystic fibrosis with meconium ileusC Microvillus inclusion diseaseD Cowrsquos milk protein intoleranceE Lactose intolerance
3 What is the investigation of choice Choose ONE answer ONLY from the followingA Rectal biopsy with staining for acetylcholine receptorsB Immunoreactive trypsinC Gastrointestinal endoscopy and biopsyD Stool microscopy and cultureE Stool reducing substances
Case 2A 4-year-old boy presents with a 3 d history of jaundice and a florid rash He has had orange urine and there is no change in his stool colour His family originate from Kosovo and have lived in the UK for the last 8 years He has never left the UK There is no history of blood transfusion or sex-ual abuse The grandmother was recently diagnosed with hepatitis B
On examination he is well apyrexial and mildly jaundiced with cervical and axillary lymphadenopathy He has an exten-sive papular rash over the face extremities and trunk (Figure 2) There is 3 cm hepatomegaly with no splenomegaly or ascites Examination is otherwise normal
Figure 1 abdominal X-ray of baby
Paediatrics and child health 184 202 copy 2008 elsevier ltd all rights reserved
self-assessment
Initial investigations are as follows
haemoglobin 110 gdl (113ndash135)
White blood cell count 108 times 109litre (50ndash150)
Platelet count 278 times 109litre (150ndash400)
inr 10 (08ndash12)
aPt ratio 10 (08ndash13)
sodium 140 mmollitre (135ndash145)
Potassium 42 mmollitre (35ndash50)
Urea 56 mmollitre (25ndash75)
creatinine 65 μmollitre (45ndash120)
total bilirubin 66 μmollitre (0ndash15)
conjugated bilirubin 23 μmollitre (0ndash10)
alanine aminotransferase (alt) 2033 iUlitre (0ndash35)
alkaline phosphatase 987 iUlitre (71ndash234)
Gamma-glutamyl transferase (GGt) 870 iUlitre (0ndash51)
1 What is the name of this rash Choose ONE answer ONLY from the followingA Erythema multiformeB Erythema migransC GianottiminusCrosti syndromeD EczemaE Dermatitis herpetiformis
2 What is the most likely diagnosis Choose ONE Answer ONLY from the followingA Autoimmune hepatitisB Hepatitis BC Hepatitis DD Wilson diseaseE Alpha-1 antitrypsin deficiency
3 What is the best means of management Choose ONE answer ONLY from the followingA Isolation until the jaundice disappearsB ImmunosuppressionC Copper chelating agents and genetic counsellingD Patient and family education with consideration of
antiviral agentsE Liver transplantation
Case 3A 10-month-old boy presents with 3 weeks of vomiting and constipation ndash he is passing hard stools every 2ndash3 days He has fallen from the 9th to below the 04th centile in the last 6 weeks He passed meconium within the first 24 h of life On examina-tion he looks pale and there are some dysmorphic features ndash a short nose long philtrum and wide mouth He has normal heart sounds with a grade 3 ejection systolic murmur loudest at the upper right sternal edge Examination is otherwise normal
Initial investigations are as follows
haemoglobin 91 gdl (113ndash141)
total white blood cell count 124 times 109litre (60ndash170)
Platelet count 407 times 109litre (150ndash400)
sodium 144 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 78 mmollitre (25ndash75)
creatinine 78 μmollitre (45ndash120)
albumin 52 glitre (35ndash50)
corrected calcium 384 mmollitre (238ndash263)
Phosphate 167 mmollitre (099ndash157)
1 What is the most likely diagnosis Choose ONE answer ONLY from the followingA HyperparathyroidismB Acute leukaemiaC Williams syndromeD Hypervitaminosis DE Familial hypocalciuric hypercalcaemia
2 Which investigation would be most useful in establishing the diagnosis Choose ONE answer ONLY from the followingA Intact parathyroid hormone assayB Blood filmC Fluorescent in-situ hybridization for 7q1123 deletionD 25-hydroxyvitamin D assayE Urine calciumcreatinine ratio
3 Which of the following treatments would not be suitable for this patient Choose ONE answer ONLY from the followingA Low calcium dietB Normal saline infusionC FurosemideD CorticosteroidsE Bisphosphonates
Case 4A 10-week-old girl presents with a 2-day history of poor feed-ing Her mother has been concerned about weakness since birth She only has a flicker of movement in the arms none in the legs and has a weak cry She has been passing urine and opening her bowels normally She was born at full term by normal delivery and did not require any resuscitation at birth Normal fetal movements were felt antenatally and there was no polyhydramnios She is the first child of non- consanguineous parents and there is no significant family his-tory On examination she is alert and fixing and following appropriately She has a weak cry and a weak suck There is reduced central and peripheral tone with marked head lag
Figure 2 rash found on examination
Paediatrics and child health 184 203 copy 2008 elsevier ltd all rights reserved
self-assessment
Muscle power is grade 3 out of 5 in the arms and legs There is no muscle or tongue fasciculation and she has absent reflexes throughout The remainder of the examination is normal
Electromyogram shows irregular polyphasic motor unit potentials with marked instability consistent with a dener-vating and re-innervating process (Figure 3)
1 Which of the following additional investigations may be helpful Choose ONE answer ONLY from the followingA Nerve conduction studiesB Creatine kinase assayC Muscle biopsyD SMN1 gene analysisE All of the above
2 What is the most likely cause of this childrsquos symptoms Choose ONE answer ONLY from the followingA Congenital myotonic dystrophyB Duchenne muscular dystrophyC PraderminusWilli syndromeD Spinal muscular atrophyE Mitochondrial myopathy
3 What is the mode of inheritance of this disease Choose ONE answer ONLY from the followingA X-linked recessiveB Autosomal recessiveC Autosomal dominantD MitochondrialE Sporadic
Case 5A 13-year-old girl presents with a 3-week history of fever up to 40degC night sweats and headache She has a reduced appetite with some weight loss She has no other specific symptoms She was on holiday in China 7 months ago On examination she looks well and has a temperature of 387degC There is no lymphadenopathy and no rashes Examination is entirely normal
Results of investigations are as follows
haemoglobin 126 gdl (120ndash160)
total white blood cell count 132 times 109litre (43ndash108)
neutrophil count 115 times 109litre (25ndash75)
Platelet count 244 times 109litre (150ndash400)
Blood film neutrophilia with left shift
erythrocyte sedimentation rate 63 mmh (1ndash20)
c-reactive protein 219 mglitre (0ndash5)
Blood culture Streptococcus intermedius
from anaerobic bottle only
csf culture negative
Magnetic resonance imaging (MRI) of the brain shows acute frontal sinusitis with a large intracranial frontal extra-dural empyema (Figure 4)
1 Which of the following would be appropriate management Choose ONE answer ONLY from the followingA A 12-week course of intravenous antibioticsB Drainage of the frontal sinus followed by 2 weeks of
intravenous antibioticsC Drainage of the empyema followed by 2 weeks of
intravenous antibioticsD Drainage of the empyema and the frontal sinus
followed by 2 weeks of oral antibiotics
1151
1152
1153
1154
1155
1156
1157
1158
1159
1200
50ms 1mV
Figure 3 electromyogram recording from the patient Figure 4 Parasagittal section from mri scan of patient
Paediatrics and child health 184 204 copy 2008 elsevier ltd all rights reserved
self-assessment
E Drainage of the empyema and the frontal sinus followed by 8 weeks of intravenous antibiotics
2 Streptococcus intermedius is a potential pathogen in which of the following infections Choose ONE answer ONLY from the followingA Liver abscessB Urinary tract infectionC MeningitisD Thoracic empyemaE Pneumonia
3 Which of the following statements regarding lsquopyrexia of unknown originrsquo in children is false Choose ONE answer ONLY from the followingA Malignancy is the underlying pathology in 5ndash15 of
casesB An aetiology will be found in over 90 of casesC The most common cause is infectionD A rheumatological cause is found in 10ndash20 of casesE Familial Mediterranean fever can occur in children of
non-Mediterranean ethnicity
Answers
Case 11 AThe anion gap is a useful tool to differentiate the causes of a metabolic acidosis It is calculated by the equation
Anion gap = [Na K ] [Cl HCO ]3+ + minus minus+ minus +
It represents the effect of unmeasured anions on the plasma pH and is normally 10ndash18 mmollitre
2 CMicrovillus inclusion disease is a severe autosomal recessive enteropathy that is typically apparent within hours or days after birth It is the second most common cause of protracted diarrhoea in the newborn after infectious causes It is characterized by severe yellow watery diarrhoea and malabsorption due to hypoplasia andor atrophy of the villi of the small intestine secondary to an inherited defect in the brush border membrane This results in severe dehydration malnutrition and metabolic acidosis due to bicarbonate loss from the gut
3 CDiagnosis of microvillus inclusion disease is made on small bowel biopsy Electron microscopy findings are of intracellular brush border inclusions and densely packed apical cytoplasmic vesicular bodies indicating microvillous atrophy There is no cure Treatment is supportive with total parenteral nutrition and consideration of small bowel transplantation
Further reAding
Goulet O ruemmele f causes and management of intestinal failure
in children Gastroenterology 2006 130(suppl 1) s16ndash28
rhoads Jm Vogler rc lacey sr et al microvillus inclusion disease
In vitro jejunal electrolyte transport Gastroenterology 1991
100 811ndash817
Case 21 CGianottindashCrosti syndrome is a distinct self-limiting rash commonly associated with viral infections in children between 2 and 6 years of age It presents as multiple pink to redminusbrown papules or papulovesicles which may be pruritic and can become confluent Gianotti and Crosti initially described the exanthema as associated with hepatitis B virus and they termed it papular acrodermatitis of childhood It can occur in several viral diseases eg hepatitis A B and C coxsackie viruses and cytomegalovirus
2 BHepatitis is a syndrome characterized by inflammation or injury of liver cells which may develop into cell necrosis and subsequently fibrosis andor cirrhosis Biochemically there are raised liver enzymes The degree of transaminase elevation does not correlate with the severity of the disease process Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of viral hepatitis
3 DHepatitis B infection is transmitted via blood sexually or vertically Infection may be acute or chronic Diagnostic markers are the presence of surface antigen (HBsAg) and HBV DNA The presence of e antigen (HBeAg) indicates high infectivity Infected newborns have a 95 risk of becoming carriers this risk decreases with infection acquired later in childhood Approximately 15ndash25 of HBV carriers will die from cirrhosis or hepatocellular carcinoma Extrahepatic findings are more common in older children and include membranous glomerulonephritis and GianottiminusCrosti syndrome Fulminant hepatic failure occurs in severe cases resulting in persistent jaundice encephalopathy and coagulopathy Management includes counselling family members monitoring for ongoing liver disease and consideration of antiviral therapy
Further reAding
Brandt O abeck d Gianotti r Burgdorf W Gianotti crosti
syndrome J Am Acad Dermatol 2006 54 136ndash145
slowik mK Jhaveri r hepatitis B and c viruses in infants and
young children Semin Pediatr Infect Dis 2005 16 296ndash305
Case 31 CHypercalcaemia is uncommon in infancy The most common symptoms in this age group are irritability vomiting and constipation It may be a manifestation of Williams syndrome vitamin D or calcium excess as well as disorders associated with reduced bone formation such as hypophosphatasia or increased bone resorption such as malignancy Occasionally
Paediatrics and child health 184 205 copy 2008 elsevier ltd all rights reserved
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-
SympoSium neonatology
8 Hawdon Jm Ward platt mp mcphail S Cameron H Walkinshaw Sa
prediction of impaired metabolic adaptation by antenatal Doppler
studies in small for gestational age fetuses Arch Dis Child 1992
67 787ndash792
9 Deshpande S Hawdon Jm et al adaptation to extrauterine life in
Rodeck C Whittle m eds Fetal medicine Basic Science and Clinical
practice edinburgh Churchill livingstone 1999
10 Ward platt m Deshpande S metabolic adaptation at birth Semin
Fetal Neonatal Med 2005 10 341ndash350
11 eyre Ja Stuart ag Forsyth RJ Heaviside D Bartlett K glucose
export from the brain in man evidence for a role for astrocytic
glycogen as a reservoir of glucose for neural metabolism Brain Res
1994 28 349ndash352
12 Hawdon Jm Ward platt mp aynsley-green a patterns of metabolic
adaptation for preterm and term infants in the first neonatal week
Arch Dis Child 1992 67 357ndash365
13 Hawdon Jm Ward platt mp aynsley-green a prevention and
management of neonatal hypoglycaemia Arch Dis Child Fetal
Neonatal Ed 1994 70 F60ndash64
14 Hawdon Jm Hypoglycaemia and the neonatal brain Eur J Paediatr
1999 158 S9ndash12
15 massieu l Haces ml montiel t Hernaacutendez-Fonseca K acetoacetate
protects hippocampal neurons against glutamate-mediated neuronal
damage during glycolysis inhibition Neuroscience 2003 120
365ndash378
16 yamada Ka Rensing n thio ll Ketogenic diet reduces
hypoglycaemia-induced neuronal death in young rats Neurosci Lett
2005 385 210ndash214
17 nehlig a Brain uptake and metabolism of ketone bodies in animal
models Prostaglandins Leukot Essent Fatty Acids 2004 70
265ndash275
18 Hernaacutendez mJ Vannucci RC Salcedo a Brennan RW Cerebral blood
flow and metabolism during hypoglycemia in newborn dogs
J Neurochem 1980 35 622ndash628
19 Vannucci RC nardis ee Vannucci SJ Campbell pa Cerebral
carbohydrate and energy metabolism during hypoglycaemia in
newborn dogs Am J Physiol 1981 256 H1659ndashH1666
20 anwar m Vannucci RC autoradiographic determination of regional
cerebral blood flow during hypoglycaemia in newborn dogs Pediatr
Res 1988 24 41ndash45
21 Hawdon Jm Williams aF et al Formula supplements given to
healthy breastfed preterm babies inhibit postnatal metabolic
adaptation results of a randomised controlled trial Arch Dis Child
2000 82 a30
paeDiatRiCS anD CHilD HealtH 184 16
22 de Rooy l Hawdon Jm nutritional factors that affect the postnatal
metabolic adaptation of full-term small- and large-for gestational
age infants Pediatrics 2002 109 e42
23 Hawdon Jm Hypoglycaemia and brain injury ndash when neonatal
metabolic adaptation fails in levene m ed Fetal and neonatal
neurology and neurosurgery edinburgh Churchill livingstone in
press
24 Hussain K Congenital hyperinsulinism Semin Fetal Neonatal Med
2005 10 369ndash376
25 acolet D Diabetes in pregnancy Caring for the Baby after Birth
CemaCH 2007 2
26 Hussain K Sharief n the inaccuracy of venous and capillary blood
glucose measurement using reagent strips in the newborn period
and the effect of haematocrit Early Hum Dev 2000 57 111ndash121
27 Hawdon Jm Disorders of blood glucose homeostasis in the neonate
in Rennie Jm ed Robertonrsquos textbook of neonatology 4th edn
edinburgh Churchill livingstone 2005
28 Deshpande S Ward platt mp the investigation and management
of neonatal hypoglycaemia Semin Fetal Neonatal Med 2005 10
351ndash361
Practice points
bull identify risk factors for impaired metabolic adaptation
bull Clinical monitoring including accurate blood glucose
measurement for at-risk babies
bull Feed at-risk babies soon after birth and maintain thermal
homeostasis
bull take first blood glucose level at 3ndash4 h of age
bull intervene in at-risk baby with no clinical signs if two
consecutive blood glucose measurements lt 20 mmollitre
bull intervene in any baby with blood glucose measurement
lt 10 mmollitre
bull intervene in any baby with abnormal clinical signs regardless
of blood glucose level
bull investigate for underlying cause of failure of metabolic
adaptation
bull maintain lactation and breast feeding
5 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Resuscitation of the term and premature babyJonathan Wyllie
Abstractalthough most newly born babies establish normal respiration and
circulation without help up to 1minus2 may require some resuscitation
or stabilization Babies who do not establish adequate regular normal
breathing or who have a heart rate of less than 100 beatsmin or other
problems such as prematurity may require assistance the differences in
approach to the resuscitation of such babies originate in the physiology
and pathophysiology of acute asphyxia at birth However management
of airway and breathing remain the key features of resuscitation and
where cardiac depression has occurred this is nearly always due to hy-
poxia secondary to respiratory compromise therefore most babies will
respond within 2minus3 min of effective aeration of the lungs and the need
for intubation chest compressions or drugs is rare the international
liaison Committee on Resuscitation (ilCoR) evaluated evidence in 2000
and 2005 in order to provide guidelines for resuscitation they will do
so again for 2010 this evidence is limited in terms of both quantity and
quality and controversies still exist more research is needed to ensure
that our future actions are based upon evidence rather than history this
article will review the recommended approach to resuscitation as well as
some newer evidence
Keywords guidelines neonatal newborn premature resuscitation
Background
In the UK 669 601 babies were born alive in 2006 and most made the transition to extrauterine life without problems Those babies who did not establish adequate regular normal breathing or who had a heart rate of less than 100 beatsmin may have required assistance1 Factual evidence concerning the true requirement for resuscitation at birth is sparse Up to 10 of newborns may require some assistance to begin breathing with less than 1 needing extensive resuscitation2 However just because a baby received resuscitation does not necessarily mean that it was required and rates of intervention may be altered by educa-tion34 or the personnel present at deliveries5 In a UK tertiary centre with a standard approach to resuscitation at birth up to 12 of all babies received some airway assistance with just over 1 being intubated3 In Sweden only 1 of babies over 2500 g required mask or endotracheal tube ventilation at birth of which most responded to the former4
Jonathan Wyllie MBChB FRCPCH is Consultant Neonatologist at the James
Cook University Hospital Marton Road Middlesbrough TS4 3BW UK
paeDiatRiCS anD CHilD HealtH 184 16
Sometimes it is possible to predict babies who are likely to have respiratory depression at birth and to have appropriate per-sonnel present at delivery Guidelines for attendance at deliveries will vary with institution but even when almost 40 of deliv-eries are attended there may still be a further 15 of babies who require unexpected resuscitation5 a proportion that seems to remain whatever changes are made
The physiology of babies requiring help at birth has been summarized previously167 It allows a logical approach to resus-citation (Figure 1) when evidence is lacking and may prompt further research
Resuscitation at birth
PreparationAt birth resuscitation is more likely in babies with intrapartum evidence of significant fetal compromise those less than 35 weeksrsquo gestation those delivering vaginally by the breech and in multiple births Personnel trained in newborn resuscitation should be available at every delivery1 Someone experienced in tracheal intubation and advanced resuscitation should also be easily available for normal low-risk deliveries in hospital and ideally in attendance for deliveries with an increased likelihood of needing resuscitation In the latter cases the equipment and environment can be prepared beforehand including a discussion with the parents Wash your hands put on gloves and consider what help may be needed
Cord clampingAt birth it has long been known that delay in clamping the cord will lead to less anaemia in babies and reduce subsequent iron deficiency8 However few hospitals have practised this interven-tion due to worries about hypothermia and the need to resusci-tate or stabilize babies In developed countries the advantages seemed to be outweighed by the potential disadvantages A recent randomized controlled study of delayed clamping of the cord in premature babies found that the intervention group had less late-onset sepsis and fewer intraventricular haemorrhages9 This is a low-risk strategy which needs further evaluation in order to introduce it without increasing other risk factors in pre-mature deliveries
Assessment and temperature controlAssessment and temperature control for the newborn baby should occur at all deliveries The assessment indicates the need for resuscitation Babies may vary from 23 to 40+ weeksrsquo ges-tation and in weight from 500 to 5000 g They are born naked and wet and if left cannot cope with an environmental tem-perature of less than 32degC However if the term baby is imme-diately dried put skin-to-skin with the mother and covered the delivery room temperature can be as low as 25ndash28degC Obviously the smaller the baby the greater the surface area to mass ratio and the greater the risk of hypothermia Compromised babies are particularly vulnerable10 and hypothermia will lower oxygen tension11 increase metabolic acidosis12 and inhibit surfactant production13
An effective method of maintaining the temperature of prema-ture babies less than 28 weeksrsquo gestation is wrapping them with plastic before drying and then placing them under a radiant
6 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Dry the babyRemove any wet towels and cover
Start the clock or note the time
Give 5 inflation breathsLook for a response
If no increase in heart rate look for chest movement
Re-check head positionApply Jaw thrust
Repeat inflation breathsLook for a response
If no increase in heart rate look for chest movement
Try alternative airway opening manoeuvresRepeat inflation breaths
Look for a response
If no increase in heart rate look for chest movement
If the heart rate is not detectable or slow (lt60)Start compressions
3 compressions to each breath
Reassess heart rate every 30 secondsConsider venous access and drugs
Assess colour tone breathing and heart rate
Open the airway
If not breathing
If still not breathing
If no response
If still no response
When the chest is moving
If meconium present
Baby breathing wellDo not suction the airway
Baby floppy and not breathing wellConsider inspection and suction before
inflation breaths
Head in neutral position
Inflation breathsUse a well-fitting face mask
connedted to a
pressure-limited gas supply
Each breath 2ndash3 seconds
duration at 30 cm H2O for a
term baby
Get help from a second personto support the airway andor
inspect the oropharynx under
direct vision and consider
suction andor insert an
oropharyngeal airway
Chest compressionsCompvent ratio 31
Rate 120 events per minute
Ensure the chest moves with each ventilation breath
If breathingReassess heart rate and monitor baby
If heart rate is satisfactory but increasingContinue ventilation breaths at about 30 per
minute until baby is breathing adequately
If heart rate is satisfactory but increasingContinue ventilation breaths at about 30 per
minute until baby is breathing adequately
If heart rate is increasingStop compressions
Continue ventilation breaths at about 30 per
minute until baby is breathing adequately
If the chest is not movingRecheck head position and repeat inflation
breaths If competent consider intubation
If the chest is still not movingThe airway is the problem
Figure 1 newborn life support (Courtesy of the Resuscitation Council uK)
heater14 There is a small risk of hyperthermia so the temperature must be monitored carefully
An assessment is made of the babyrsquos colour tone respira-tions and heart rate127 The most important of these is heart rate and a stethoscope is more reliable than cord pulsation15 How-ever saturation monitors may offer a more reliable assessment of both heart rate and colour16 but their interpretation requires a detailed knowledge of normal saturations at birth at differing gestations A baby who is apnoeic and floppy in the absence of neurological disease is unconscious and likely to be in terminal apnoea however this does not change the initial approach other
paeDiatRiCS anD CHilD HealtH 184 167
than the need to summon help early APGAR scores are never calculated to guide resuscitation
Airway
If a baby is in primary apnoea then with an open airway the first gasp will start to aerate the lungs and most babies will be able to lsquoresuscitatersquo themselves as shown in physiological stud-ies on animals Neutral positioning of the babyrsquos head chin lift jaw thrust oropharyngeal airways and endotracheal intubation may all be helpful in certain situations if performed correctly17
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Endotracheal intubationThe placement of an endotracheal tube has long been the gold standard of airway control and this remains true in the unconscious baby if it is correctly sized placed and fixed in a timely manner However experience is directly related to effec-tiveness in endotracheal intubation1819 and the success rate of less experienced clinicians such as a resident (STA1-3) or a fel-low (STA3-5) is lower varying between 33 and 68 Even senior neonatologists often take longer than guidelines recom-mend19 Experienced clinicians may judge correct endotracheal position visually or by an increase in heart rate with the first breaths but detection of exhaled carbon dioxide will give more rapid confirmation in larger babies12171920 and this can be par-ticularly useful for less experienced clinicians or those supervis-ing them However not all systems for the detection of exhaled carbon dioxide work in the smallest premature infants
Laryngeal masksLaryngeal masks may be effective for ventilating term newborn babies but there are few data for small premature infants There have been reports of dislodged laryngeal airways during paedi-atric arrests when chest compressions have been administered Although success of placement at first attempt by paediatri-cians is greater with a laryngeal mask than with an endotra-cheal tube21 the only and small randomized controlled trial in the delivery room favoured endotracheal intubation when per-formed by an anaesthetist22 Based mainly upon case reports the laryngeal mask can be recommended when positioning and mask ventilation and endotracheal intubation have failed to secure the airway but not as yet as a primary method of airway control
MeconiumIn 2000 Wisewell et al23 reported a large randomized controlled trial showing that tracheal intubation and suctioning of meco-nium-stained but vigorous babies at birth did not reduce the incidence or severity of meconium aspiration syndrome More recently another randomized trial has now shown that suction-ing on the perineum similarly offers no benefit24 Neither of these practices is recommended but intubation and suction of meconium from the trachea of non-vigorous babies born through meconium-stained liquor is still recommended
Breathing
In the apnoeic baby the first breaths establish the resting lung volume and aerate the fluid-filled alveoli This mechanical effect aided by surface tension within the alveoli causes the initial fall in pulmonary vascular resistance Experimentally this effect occurs even if the lungs are ventilated with nitrogen but is increased when air is used presumably due to the vasodilator effect of 21 oxygen The mechanical stretching of the lung also triggers the activation of cyclo-oxygenase beginning the production of prostacyclin Bradykinin is produced which has a further direct vasodilator effect and also possibly via prostacyclin Therefore adequate airway control and passive ventilation is vital not only because babies requiring resuscitation at birth have an almost uniformly respiratory aetiology but also in order to promote post-natal adaptation and reverse any maladaptation
paeDiatRiCS anD CHilD HealtH 184 16
In term babies peak ventilatory pressures of 20ndash30 cmH2O may be required but the minimal pressure needed to achieve an improvement in heart rate should be used or if there is no response chest wall movement Longer breaths at lower pressure may be more effective in displacing alveolar fluid and establish-ing the resting lung volume in lungs with sufficient surfactant and may improve initial oxygenation However premature new-borns are obviously physiologically and anatomically less pre-pared for delivery than infants at term Over-inflation has been implicated in histological lung damage in animal models and high tidal volumes appear to be equally damaging whether given before or immediately after administration of surfactant How-ever the same effect is not seen if these excessive tidal volumes are delivered 15 min after administration of surfactant2526 It is now thought that both excess end expiratory volume and inad-equate end-expiratory volume may cause lung damage2728 In premature infants it would therefore seem sensible to use lower pressures of 20ndash25 cmH2O12 delivered in a controlled way to prevent over-inflation and to apply positive end-expiratory pres-sure (PEEP) to prevent damage from under-inflation PEEP also improves both lung compliance and gas exchange2930 Without PEEP the airways collapse during the expiratory phase in animal models of newborn resuscitation
If animal data can be extrapolated it would also seem appro-priate to give surfactant as soon as possible to premature babies in order to ameliorate damage2526
The majority of newborn infants requiring resuscitation will re-establish regular respiration after administration of a few breaths which may be due to Headrsquos paradoxical reflex by which the inflation triggers an inspiratory effort
VentilationOnce the lungs are aerated if the newborn remains apnoeic ventilation should be continued at 30ndash60 breathsmin avoiding hyperventilation and using the minimum pressure possible to maintain a heart rate greater than 100 beatsmin
Face mask the majority of infants who require ventilation receive it via a face mask This may be attached to a bagvalve system with a spring lsquoblow offrsquo system or a lsquoT-piecersquo with a set flow and pressure It is important to realize that the bagvalve system is flow sensitive and that the harder the operator presses the greater the flow and the higher the delivered pressure In fact 60 cmH2O can be achieved with vigorous squeezing of a self-inflating bag Therefore it may be advantageous that most opera-tors are unlikely to be as effective as they suppose in creating a seal with the mask31 This is a skill that requires tuition and prac-tice31 In delivering a set pressure T-piece systems such as the Tom Thumbcopy or Neopuffcopy perform better than any bagminusvalve system but require a gas supply There is no evidence that lung compliance can be assessed using any bag system
Continuous airway pressure case series have suggested that early or delivery room use of continuous positive airway pres-sure (CPAP) in premature babies may reduce chronic lung dis-ease There have been two randomized trials of which one was a pilot study The data from the COIN trial do not show any advan-tage other than a reduction in intubation and surfactant use in the intervention group However an excess of pneumothorax
8 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
was also reported The Vermont Oxford Network and the SUP-PORT trials will provide further data but at present the delivery room use of CPAP cannot be widely recommended and should be limited to those units experienced in its use or taking part in research
Air or oxygen oxygen has been in widespread use for resuscita-tion at birth since the 1930s and even hyperbaric oxygen was seriously supported in the 1960s For many years there have been concerns about tissue damage from oxygen deprivation during and after resuscitation It became evident in the 1950s that unrestricted oxygen therapy could have serious conse-quences for future vision More recently concerns have been raised about potential adverse effects on respiratory physiology cerebral circulation and tissue damage from oxygen free radicals even during resuscitation A meta-analysis of four human studies demonstrated a reduction in mortality and no evidence of harm in infants resuscitated in air versus 100 oxygen3233 However there are several significant methodological concerns with these studies and the results should be interpreted with caution There is insufficient evidence to recommend any specific concentration of oxygen to be used for newborn resuscitation Monitoring the oxygen saturation of babies may be helpful but as yet there are no time-related normal target ranges and healthy term babies may take up to 10 min to achieve preductal oxygen saturation of greater than 95 and up to 60 min to achieve this postductally
There is therefore equipoise which would be open to an appropriate randomized controlled trial In the meantime the evidence only supports use of either 21 or 100 oxygen It is provoking to realize that if air had been in constant use since the 1930s there would be insufficient evidence for use of supple-mental oxygen
Circulation
Early resuscitation (temperature control airway breathing) provides oxygenated blood in the pulmonary arterioles which if returned to the heart causes the rate to increase34 If due to acidosis and hypoxia the circulation is ineffective then chest compressions may be needed They should be commenced when the heart rate remains below 60min despite effective airway and breathing management127 The best technique is using two hands to encircle the chest1 A ratio of three compressions to one breath is internationally accepted127 but has no evidence to support it Research has shown that neither compressions nor drugs will work in this situation without oxygenated blood so effective lung aeration and ventilation is essential A logical approach would be to fill the alveoli with air and to compress the chest until they are empty However training and teamwork require an agreed ratio which has therefore not changed since guidelines were first agreed internationally Success is assessed by an increase in heart rate which should therefore be assessed every 30 s Compressions stop when the spontaneous heart rate is greater than 60 beatsmin
In hypoxic newborn animal models successful resuscitation can restore cardiac output and blood pressure to levels above baseline within 5ndash10 min However it should be noted that there is a decline to 30 lower than basal levels within 2 h and that blood pressure is relatively spared suggesting an even greater
paeDiatRiCS anD CHilD HealtH 184 16
reduction in tissue perfusion This should be considered in the later care of any neonate who was hypoxic at birth
Drugs
Neonatal bradycardia at birth is almost always due to hypoxia plusmn acidosis and therefore drugs are rarely needed Adrenaline (epi-nephrine) is reported as being used in between 1 and 4 babies per 2000 births which is a large variation in practice Reported success is also variable and must be interpreted in light of this variation The use of drugs in extremely premature infants is con-troversial Some data suggested good outcomes for babies below 28 weeksrsquo gestation given adrenaline but these were flawed by high numbers of babies receiving resuscitative drugs some before the airway had been appropriately managed Audit data now suggest a poor outcome such that many clinicians would now council against the use of adrenaline and other drugs to resuscitate extremely premature newborn babies
Adrenaline (epinephrine)In 2003 a Cochrane review of randomized controlled trials involv-ing adrenaline use for resuscitation of neonates was unable to identify a single clinical trial35 Despite the lack of human neo-natal data animal models show the potential of adrenaline in asphyxial cardiac arrest and it is reasonable to use it when ade-quate ventilation and chest compressions have failed to increase the heart rate above 60 beatsmin Use 10ndash30 μgkg intrave-nously and preferably via an umbilical venous line The tracheal route cannot be recommended but if used it is likely that doses within this range will be ineffective and 100 μgkg might be tried However the safety of such doses has not been studied
BicarbonateThe use of bicarbonate has long been controversial but many of the concerns relate to the rapid correction of acidosis in neonates after resuscitation or the routine use of bicarbonate infusion nei-ther of which can be advocated There are no published human neonatal data to support its use although some exist from animal studies Animal data have also shown that the binding of adren-aline to receptors in the myocardium is significantly impaired by lactic acidosis and recent work on human lymphocyte beta-adrenergic receptors supports this view Whether this is also true of the more important alpha receptors is unknown In practice reversing intracardiac acidosis may improve myocardial function and assist in achieving a return of spontaneous circulation 1ndash2 mmolkg of bicarbonate may be given but this remains a contro-versial area
VolumeVolume expansion should only be given when it is suspected that the baby has suffered blood loss or the infant appears to be in shock (pale poor perfusion weak pulse) and has not responded adequately to other resuscitative measures If there is no history suggestive of blood loss shock is most likely to be due to myo-cardial dysfunction in which case fluids should be administered cautiously The most logical replacement fluid would be blood but in its absence isotonic crystalloid rather than albumin is the solution of choice given in 10 mlkg aliquots and observing the response Three randomized trials in neonates have shown
9 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
isotonic crystalloid to be as effective as albumin for the treat-ment of hypotension but none has examined either the relative or actual effectiveness in resuscitation A recent blinded randomized study comparing normal saline albumin or no volume expansion in a normovolaemic asphyxiated neonatal animal model showed that volume expansion was not beneficial and made a number of parameters worse36
NaloxoneNaloxone is not recommended as part of the initial resuscita-tion of newborns with respiratory depression Before it is given supporting ventilation should have restored the heart rate and colour The dose is 100 μgkg intravenously or intramuscularly Tracheal administration cannot be recommended Although administration of naloxone to neonates who have been exposed to maternal opioids during labour is a practice of long-standing it lacks the proper evidence of efficacy
Non-response to resuscitation
There are few more frightening situations professionally than applying the correct interventions in resuscitating or stabilizing a baby and getting no response Each stage must be adequately performed before moving onto the next and this requires regular reassessment When experienced help is needed at a newborn resuscitation it is usually the airway and ventilation that require correction If the heart rate does not increase this usually means that the lungs have not been successfully aerated In some cases however it may mean that the heart cannot respond as the cir-culation is inadequate In this situation the only way to check that the lungs have been successfully aerated is to see the chest move with ventilation or to obtain evidence of ventilation from a detector of exhaled carbon dioxide If you do not see chest movement after another five breaths the most likely cause is an obstructed airway either due to incorrect positioning or because the jaw has not been drawn forwards An oropharyngeal airway can be very helpful at this point especially in the term baby Only very occasionally is the airway blocked by mucus vernix blood or meconium but if the airway is guaranteed and there is no heart rate response or chest movement this should be sought by direct suction of the trachea even in the absence of any meconium staining of liquor Pneumothoraces can occur spontaneously after delivery but are rare at resuscitation carried out with pressure-limited devices Equally rare are diaphragmatic hernias that have not been diagnosed antenatally giving problems at resuscitation
If the chest is moving but the heart rate has not responded to resuscitation consider rare possibilities such as fetal blood loss pneumothorax or heart block (mothers with undiagnosed systemic lupus erythematosis delivered for fetal bradycardia) as possibilities With adequate ventilation there is no evidence of oxygen concentrations less than 100 being responsible for prolonged bradycardia or failure to respond although current practice would support increasing the delivered oxygen concen-tration if resuscitation had been commenced using air
Outcome
The prognosis for the full-term baby subjected to sudden acute asphyxia is usually good provided the episode does not last for
paeDiatRiCS anD CHilD HealtH 184 17
long Most babies resuscitated from primary apnoea have no sequelae secondary to the resuscitation Many babies who start to breathe again regularly within 20 min of the circulation being restored recover completely but it is rare for a baby who is still gasping after 30 min to recover
The prognosis for the preterm baby of less than about 34 weeksrsquo gestation subjected to severe acute anoxia is less predict-able This is because of the risk of secondary intraventricular haemorrhage or periventricular intracerebral haemorrhage andor infarction after even a relatively brief asphyxial episode espe-cially in the period immediately around birth
The effects of chronic hypoxia are also difficult to predict but a reasonably clear idea of the extent of the problem should be obtainable within 36ndash48 h of the original chronic asphyxial insult A mild short-lasting state of hyperexcitability usually car-ries a good prognosis even if there is seizure activity but more severe symptoms can be associated with permanent handicap This is seen especially in infants with encephalopathy requiring ventilation
REFERENCEs
1 Biarent D Bingham R Richmond S et al european Resuscitation
Council guidelines for Resuscitation 2005 Section 6 paediatric life
support Resuscitation 2005 67(suppl 1) S97ndashS133
2 international liaison Committee on Resuscitation part 7 neonatal
resuscitation Resuscitation 2005 67 293ndash303
3 Singh J Santosh S Wyllie J mellon a effects of a course in
neonatal resuscitation - evaluation of an educational intervention
on the standard of neonatal resuscitation Resuscitation 2006 68
385ndash389
4 palme-Kilander C methods of resuscitation in low-apgar-score
newborn infants - a national survey Acta Paediatr 1992 81
739ndash744
5 Kroll l twohey l Daubeney p et al Risk factors at delivery and
the need for skilled resuscitation Eur J Obstet Gynecol Reprod Biol
1994 44 175ndash177
6 Wyllie Jp Resuscitation of the newborn The Foundation Years
2007 3(4) 153ndash157
7 Richmond S ed newborn life Support Resuscitation at Birth
london Resuscitation Council 2006
8 Ceriani Cernadas Jm Carroli g pelligrine l et al the effect of timing
of cord clamping on neonatal venous hematocrit values and clinical
outcome at term a randomized controlled trial Pediatrics 2006
117 e779ndashe786
9 mercer JS Vohr BR mcgrath mm padbury JF Wallach m oh W
Delayed cord clamping in very preterm infants reduces the incidence
of intraventricular hemorrhage and late-onset sepsis a randomized
controlled trial Pediatrics 2006 117 1235ndash1242
10 Dahm lS James lS newborn temperature and calculated heat loss
in the delivery room Pediatrics 1972 49 504ndash513
11 Stephenson J Du J tk o the effect of cooling on blood gas
tensions in newborn infants J Pediatr 1970 76 848ndash852
12 gandy gm adamsons Jr K Cunningham n Silverman Wa James lS
thermal environment and acid-base homeostasis in human infants
during the first few hours of life J Clin Invest 1964 43 751ndash758
13 gluck l Kulovich mV eidelman ai et al Biochemical development
of surface activity in mammalian lung pulmonary lecithin synthesis
0 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
in the human fetus and newborn and etiology of the respiratory
distress syndrome Pediatr Res 1972 6 81ndash99
14 Vohra S Roberts RS Zhang B Janes m Schmidt B Heat loss
prevention (Help) in the delivery room a randomised controlled
trial of polyethylene occlusive skin wrapping in very preterm infants
J Pediatr 2004 145 750ndash753
15 owen CJ Wyllie Jp Determination of heart rate in babies at birth
Resuscitation 2004 60 213ndash217
16 orsquoDonnell Cp Kamlin Co Davis pg Carlin JB morley CJ Clinical
assessment of infant colour at delivery Arch Dis Child Fetal
Neonatal Ed 2007 92 F465ndashF467
17 international liaison Committee on Resuscitation part 13 neonatal
Resuscitation guidelines Circulation 2005 112(suppl 24)
iV188ndashiV195
18 leone ta Rich W Finer nn neonatal intubation Success of
pediatric trainees J Pediatr 2005 146 638ndash641
19 orsquoDonnell Cp Kamlin Co Davis pg morley CJ endotracheal
intubation attempts during neonatal resuscitation success
rates duration and adverse effects Pediatrics 2006 117
e16ndash21
20 Repetto Je Donohue pa-CpK Baker SF Kelly l nogee lm use of
capnography in the delivery room for assessment of endotracheal
tube placement J Perinatol 2001 21 284ndash287
21 gandini D Brimacombe JR neonatal resuscitation with laryngeal
mask airway in normal and low birth weight infants Anesth Analg
1999 89 642ndash643
22 esmail n Saleh m ali a laryngeal mask airway versus endotracheal
intubation for apgar score improvement in neonatal resuscitation
Egypt J Anesthiol 2002 18 115ndash121
23 Wiswell te gannon Cm Jacob J et al Delivery room management
of the apparently vigorous meconium-stained neonate results of
the multicenter international collaborative trial Pediatrics 2000
105 1ndash7
24 Vain ne Szyld eg prudent lm Wisewell te aguilar am Vivas ni
oropharyngeal and nasopharyngeal suctioning of meconium-stained
neonates before delivery of their shoulders multicentre randomised
controlled trial Lancet 2004 364 597ndash602
25 Bjorklund lJ ingimarsson J Curstedt t larsson a Robertson B
Werner o lung recruitment at birth does not improve lung function
in immature lambs receiving surfactant Acta Anaes Scand 2001 45
986ndash993
26 Bjorklund lJ ingimarsson J Curstedt t et al manual ventilation
with a few large breaths at birth compromises the therapeutic effect
of subsequent surfactant replacement in immature lambs Pediatr
Res 1997 42 348ndash355
paeDiatRiCS anD CHilD HealtH 184 17
27 taskar V John J evander e Robertson B Jonson B Surfactant
dysfunction makes lungs vulnerable to repetitive collapse and re-
expansion Am J Respir Crit Care Med 1997 155 313ndash320
28 muscedere Jg mullen JB gan K Slutsky aS tidal ventilation at low
airway pressures can augment lung injury Am J Respir Crit Care Med
1994 149 1327ndash1334
29 nilsson R grossman g Robertson B Bronchiolar epithelial lesions
induced in the premature rabbit neonate by short periods of artificial
ventilation Acta Pathol Microbiol Scand 1980 88 359ndash367
30 probyn me Hooper SB Dargaville pa et al positive end expiratory
pressure during resuscitation of premature lambs rapidly improves
blood gases without adversely affecting arterial pressure Pediatr
Res 2004 56 198ndash204
31 Wood Fe morley CJ Dawson Ja et al improved techniques
reduce face mask leak during simulated neonatal resuscitation
study 2 Arch Dis Child Fetal Neonatal Ed in press doi101136
adc2007117788
32 tan a Schulz a orsquoDonnell CpF Davis pg air versus oxygen for
resuscitation of infants at birth Cochrane Database Syst Rev 2004
(3) CD002273
33 Davis pg tan a orsquoDonnell Cp Schulze a Resuscitation of newborn
infants with 100 oxygen or air a systematic review and meta-
analysis Lancet 2004 364 1329ndash1333
34 Dawes g Fetal and neonatal physiology Chicago year Book
publisher 1968 p 141ndash159
35 Ziino aJa Davies mW Davis pg epinephrine for the resuscitation
of apparently stillborn or extremely bradycardic newborn infants
Cochrane Database Syst Rev 2003 (2) CD003849
36 Wyckoff m garcia D margraf l perlman J laptook a Randomized
trial of volume infusion during resuscitation of asphyxiated neonatal
piglets Pediatr Res 2007 61 415ndash420
Practice points
bull Resuscitation at birth is different from that at all other times
of life
bull a standard approach can be applied to most newborn
resuscitation
bull guidelines are based on a rigorous evaluation of evidence
where possible
bull evidence is sparse but evolving
bull most preterm babies require stabilization rather than
resuscitation
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Acidndashbase physiology and blood gas interpretation in the neonateSusern tan
morag Campbell
Abstractacidndashbase balance describes the complex processes that work to main-
tain a stable extracellular pH for optimal cellular function the process
of balancing the production and neutralization of tissue acid provides a
great challenge for newborn infants who have significantly higher rates
of acid production than adults Factors which help maintain a stable
acidndashbase balance include buffers the respiratory system and renal sys-
tem Both intracellular and extracellular buffers resist changes in pH
the most important extracellular buffer system for maintaining stable
pH is the bicarbonate system in response to acidosis or alkalosis the
respiratory system balances the production of acid with the clearance
of Co2 by altering respiratory rate the kidneys provide a delayed but
sustained response to pH imbalance by excreting either acidic or alkaline
urine in response to systemic acidosis and alkalosis respectively in sick
premature infants these systems have a limited capacity completely to
control pH this review discusses the physiology of the three systems
which control acidndashbase balance patterns of clinical abnormalities in
acidndashbase status and their underlying causes are discussed We present
a systematic approach to blood gas analysis and interpretation in new-
born infants
Keywords acidosis alkalosis bicarbonate bloodndashgas analysis
metabolic pH
Introduction
Blood gas analysis is a routine procedure performed on newborn babies receiving respiratory support in the neonatal intensive care The combination of invasive and non-invasive assessment of ventilation and oxygenation enables clinicians appropriately to modify respiratory care according to each individual babyrsquos rapidly changing clinical status
Understanding the fundamentals of acidndashbase balance helps us to use blood gas analysis not only to assess respiratory sta-tus but also to provide information on metabolic status and the adequacy of tissue perfusion
Susern Tan MBBS MRCP is Clinical Fellow at the Neonatal Intensive Care
Unit 6th Floor North Wing St Thomasrsquo Hospital London SE1 7EH UK
Morag Campbell MBChB MRCP is Consultant Neonatologist at the
Neonatal Intensive Care Unit 6th Floor North Wing St Thomasrsquo
Hospital London SE1 7EH UK
paeDiatRiCS anD CHilD HealtH 184 17
What is understood by acid-base balance
Acidndashbase balance refers to the complex physiological processes used by the body to maintain a stable extracellular pH1 A serum pH within the range of 735ndash745 provides the ideal environment for cellular metabolism Maintaining a stable pH is critical as the metabolic activity of proteins is pH dependent and small changes in hydrogen ion (H+) concentration can potentially alter physio-logical function
Acids are substances that yield free H+ in solution while a base accepts H+ and in solution combines with an acid to neu-tralize it In the normal metabolic state H+ are continuously pro-duced and neutralized to maintain a steady pH balance12 The rate of H+ production is two to three times higher in neonates because of their rapid growth rates and increased acid production from protein turnover and bone mineralization The challenge of maintaining a stable pH through processing and neutralizing H+ is therefore greatest in newborn infants
Using exact values of H+ concentration to assess acidndashbase status is cumbersome and it is more commonly expressed as pH defined by the equation
pH = minuslog H+
Maintaining acidndashbase balance
The balance between production and excretion of acids in the body is controlled by buffer systems which have an immediate effect and by the respiratory and the renal systems
Buffer systemsBuffer solutions resist change in pH when acid or alkali is added due to their capacity to absorb or give up H+ The three main buffer systems in the body are the bicarbonate phosphate and protein systems1ndash3 The protein and phosphate buffer systems are intracellular and act as lsquosinksrsquo for extracellular H+ which are exchanged with intracellular potassium (K+) and sodium ions (Na+) In an acute metabolic acidosis hyperkalaemia may develop due to this H+ exchange4
The bicarbonate buffer system is extracellular and consists of a mixture of carbonic acid (H2CO3) and sodium bicarbon-ate (NaHCO3) This buffer system helps maintain a stable pH by soaking up excess H+ with HCO3
minus which in solution forms carbonic acid (H2CO3) Carbonic acid is a weak acid and readily dissociates to give CO2 which is transported in dissolved form to the lungs for excretion
H+ + HCO3minus harr H2CO3 harr H2O + CO2
The bicarbonate system therefore completes the neutraliza-tion of excess H+ and a stable plasma pH is maintained The relationships between pH HCO3
minus and CO2 in this system are described by the HendersonndashHasselbalch equation15
pH = 61 + log HCO3minus003 times CO2
where 61 is the log of the dissociation coefficient of carbonic acid and 003 the solubility of CO2 in plasma Buffers are most potent when there are equal amounts of H+ and HCO3
minus in solution The
2 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
bicarbonate system is not a potent buffer however as HCO3minus
and CO2 are readily altered by the body this system plays a very powerful role in pH homeostasis15
Respiratory regulationThe respiratory system adapts within minutes to hours as part of the acute response to acidosis This system modifies pH by balancing production of H+ with ventilatory clearance of CO2
H+ directly stimulates chemoreceptors in the respiratory cen-tre of the brainstem producing an increase in respiratory rate26 The response to respiratory acidosis is very rapid as CO2 easily diffuses across the bloodndashbrain barrier however in metabolic acidosis compensation is delayed until plasma bicarbonate fully equilibrates with cerebrospinal fluid (CSF) bicarbonate There is an inverse relationship between alveolar ventilation and partial pressure of dissolved carbon dioxide (PaCO2) a reduction in alveolar ventilation raises PaCO2 and decreases pH Changes in pH therefore affect alveolar ventilation and conversely changes in alveolar ventilation cause significant changes in pH
Renal regulationThe kidneys provide a delayed but sustained response to acidndashbase imbalances by excreting either acidic or alkaline urine In full-term and preterm babies the capacity for acid excretion and bicarbonate reabsorption is reduced as glomerular filtration rates are low and tubular function immature7 Renal function matures with gestation postnatal age and glucocorticoid and thyroid hormones78 Due to their limited capacity to preserve HCO3
minus newborn infants have lower serum bicarbonate levels and are predisposed to acidosis7
Bicarbonate is not effectively reabsorbed due to its size and electrical charge Instead intraluminal HCO3
minus combines with secreted H+ in tubular luminal fluid to produce carbonic acid which dissociates to give H2O and CO2 This CO2 diffuses into tubular cells combines with intracellular H2O and forms carbonic acid which liberates HCO3
minus and H+ HCO3minus is then
recovered to the circulation by exchange for chloride ions (Clminus) through the basal cell membrane247
Renal acid secretion occurs at all sites except the loop of Henle Primary active transport accounts for 5 and secondary for the remaining 95 of total H+ excretion Secondary trans-port involves an exchange between luminal Na+ and intracel-lular H+ Both ions bind to a membrane transport protein The Na+ concentration gradient between the tubular lumen and cells enables Na+ drag into the cell which generates energy to fuel active H+ excretion into the tubular lumen1ndash47
Quantifying acidosis
Standard base excess is a calculated value derived from PaCO2 and pH It is expressed as the mmollitre of base above or below normal buffer bases required to correct the pH to 74 at a PaCO2 of 40 mmHg A negative base excess or base deficit indicates an acidosis while a positive base excess indicates a relative alkalosis15
Anion gap is the measured difference between anions and cations in the blood
Anion gap = (Na+ + k+) minus (HCO3+Clminus)
paeDiatRiCS anD CHilD HealtH 184 17
Calculation of the anion gap enables clinicians better to define the underlying cause of a metabolic acidosis9 The common causes of an increased anion gap acidosis in neonates include lactic acidosis due to tissue hypoperfusion and hypoxia it may also be seen with certain inborn errors of metabolism and in uraemia910 The anion gap can help distinguish between the rela-tively benign non-anion gap hyperchloraemic acidosis seen in premature infants and a pathological lactic acidosis due to poor end-organ perfusion1011
Strong ion theory
Stewart described a complex acidndashbase model which proposed that H+ concentration results from the dissociation of water which is influenced by PaCO2 the strong ion difference and plasma weak acids12
Strong ions are ions that dissociate at normal body pH and include Na+ K+ and Clminus Weak acids in plasma which contrib-ute include albumin inorganic phosphate and plasma proteins their concentrations do not change with pH and are therefore a constant The effect of these factors and other unmeasured tissue ions on acidndashbase status can be quantified by the calculation of the strong ion gap (SIG)112 In the neonatal unit it is perhaps more important that we consider how principles of this model may relate to acidndashbase status rather than fully to quantify the SIG Theoretically low albumin and phosphate levels which fre-quently occur in premature infants by reducing the concentra-tion of weak acids can produce a relative alkalosis while high phosphate levels in renal failure may contribute to acidosis
Tissue oxygenation
Oxygenation is closely linked to acidndashbase status as optimal cel-lular function requires oxygen to fuel aerobic metabolism and produce energy In hypoxic conditions anaerobic metabolism predominates which is energy inefficient and results in a lactic acidosis1011
Tissue oxygen availability is related to regional blood flow haemoglobin level and haemoglobin oxygen affinity Arterial blood gases measure the partial pressure of dissolved oxygen (PaO2) which represents a small component of total oxygen con-tent the majority being transported bound to haemoglobin The relationship between percentage haemoglobin saturation (SaO2) and PaO2 is described by the sigmoidal oxyhaemoglobin disso-ciation curve which enables us to relate the two measures to each other235 The affinity of haemoglobin for oxygen is altered by local tissue factors Increases in temperature H+ PaCO2 and 23-diphosphoglycerate (DPG) levels shift the oxyhaemoglobin dissociation curve to the right reducing affinity for oxygen Decreases in temperature H+ PaCO2 and 23-DPG levels shift the curve to the left increasing oxygen affinity1ndash35 In the body haemoglobin oxygen affinity continuously changes increasing in the lungs to enable efficient oxygen uptake and decreasing at tissue level to provide efficient oxygen delivery to metabolically active tissues
Avoiding both hypoxia and hyperoxia is important in the neo-natal unit as deleterious effects of hypoxia are seen in infants with pulmonary hypertension1314 while hyperoxia is associated with an increased incidence of retinopathy of prematurity1516
3 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Clinical acidndashbase imbalances
Clinical acidndashbase imbalances can be respiratory metabolic or a mixture of both These abnormalities may be corrected by the acidndashbase regulatory mechanisms in the body in an attempt to maintain normal pH (Figure 1)
Respiratory acidosisThis occurs when any disorder leads to decreased alveolar ventilation Common causes of respiratory acidosis are listed in Table 1 Reduced respiratory clearance of CO2 means more dissolved CO2 accumulates in the plasma leading to increased production of carbonic acid and H+ Through chemoreceptor stimulation respiratory acidosis rapidly alters ventilation in an attempt to reduce CO226 Chemoreceptor mediated ventila-tory increases may only partly adjust in premature infants with underlying lung disease In babies with a sustained respiratory acidosis eg in chronic lung disease then metabolic compen-sation occurs through increased renal excretion of H+ and reabsorption of HCO3
minus slowly restoring pH to around 80 of normal47
paeDiatRiCS anD CHilD HealtH 184 17
The management of PaCO2 levels in infants receiving mechan-ical ventilation has important clinical implications Premature babies have impaired cerebral autoregulation17 and adverse neurological sequelae are reported in association with high PaCO2 levels18ndash20 Ventilation strategies which advocate lsquoper-missive hypercarbiarsquo have been developed to minimize airways damage from mechanical ventilation21 Published data suggest pulmonary benefits however the safe level of PaCO2 remains to be defined in premature infants2021
Respiratory alkalosisThis occurs when more CO2 is excreted than is produced by the body Pathological conditions leading to respiratory alkalosis are rare Hyperventilation in the neonatal setting is often iatrogenic or may be due to disorders in brainstem control of breathing including hypoxicndashischaemic encephalopathy or primary central nervous system abnormalities (see Table 1)
If respiratory alkalosis is sustained it may be compensated for by reduced reabsorption of filtered bicarbonate Reported adverse associations of low PaCO2 include periventricular leuco-malacia and intraventricular haemorrhage1922
K+
H+
Overventilation
CO2 + H2O harr H2CO3 harr H+ + HCO3ndash
Bicarbonate Buffer
Intracellular Buffer
uarr H+ excretionuarr HCO3
ndash absorption
uarr buffered H+
(NH4+ H2PO4
ndash)uarr ventilation rate
RespiratoryAcidosis
MetabolicAcidosis
darr CO2and uarr pH
RespiratoryAlkalosis
MetabolicAlkalosis
darr H+ anduarr pH
darr ventilation rate
uarrCO2
and darr pH
darr H+ excretiondarr HCO3
ndash absorption
uarrH+ and
darr pH
Brain
Brain
Intracellular Buffer
H+
K+
Sepsis
HypoxiaRDS
Metabolismand growth
Diuretics
Airwayobstruction
Neuromuscularproblems
IEM
Gastric losses
+ +
ndash -
Renal BufferRespiratory Buffer
Figure 1 mechanisms for regulation of extracellular pH iem inborn errors of metabolism RDS respiratory distress syndrome
4 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Common causes of acidndashbase imbalances
pH PCO2 H2CO3 Base excess Common neonatal causes
Respiratory acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
uarr normal normal bull upper airway obstruction choanal atresia
pierre-Robin sequence
bull lung abnormalities respiratory distress
syndrome transient tachypneoa of
newborn pneumonia meconium aspiration
syndrome pulmonary hypoplasia
congenital pulmonary malformations
bull Central hypoventilation hypoxic-ischaemic
encephalopathy intracranial haemorrhage
bull neuromuscular insufficiency congenital
myopathies congenital neuropathies
bull iatrogenic inadequate ventilatory settings
Compensated lower limit
of normal
uarr uarr gt+3
metabolic acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
normal darr ltminus3 increased anion gap
bull lactic acidosis sepsis hypoperfusion
shock necrotizing enterocolitis
bull inorganic acidosis inborn errors of
metabolism renal failure
normal anion gap
bull increased gastrointestinal H2Co3 losses
ileostomy diarrhoea
bull Renal tubular acidoses
Compensated lower limit
of normal
darr darr ltminus3
Respiratory alkalosis Uncompensated gt 745 darr normal normal bull iatrogenic excessive ventilatory settings
bull Compensatory hyperventilation hypoxic-
ischaemic encephalopathy
Compensated higher limit
of normal
darr darr ltminus3
metabolic alkalosis Uncompensated gt 745 normal uarr gt+3 bull gastric losses vomiting non-replacement
of excessive nasogastric aspirates
bull thiazide and loop diuretics
bull Hypokalaemia
Compensated higher limit
of normal
uarr uarr gt+3
Table 1
Metabolic acidosisThis frequently affects infants in the neonatal unit and has many causes1011 (see Table 1) There may be overproduction of tissue acid impaired acid clearance gastrointestinal loss of bicarbonate or an exogenous increased acid load eg chloride total paren-teral nutrition (TPN) or albumin1ndash323
Calculation of the anion gap to distinguish an increased anion gap acidosis from a non-anion gap acidosis is important both for treatment and prognosis1011 Acidosis stimulates respiratory compensation but this is limited in unstable infants Similarly renal compensation with improved HCO3
minus conservation is con-strained by tubular immaturity Treatment of the acidosis should be directed at the underlying cause eg hypoxia hypotension or excess Clminus rather than by administration of base
Metabolic alkalosisThis is unusual in neonates and is most frequently seen in infants with chronic lung disease or heart failure who are receiving diuretics Diuretics cause alkalosis by increasing renal fluid and Na+ losses An active process to reabsorb Na+ occurs in tubule cells which through enhanced H+ secretion and HCO3
minus reab-sorption produce alkalosis27
paeDiatRiCS anD CHilD HealtH 184 17
Metabolic alkalosis may also occur with excessive loss of gas-tric contents eg protracted vomiting or inadequate replacement of nasogastric aspirates (see Table 1)
Interpreting blood gases
Blood gas measurements can provide important diagnostic and prognostic information and a systematic approach to blood gas analysis is described in Table 2 The clinical management of infants with abnormal gases requires a good understanding of acidndashbase physiology and tissue oxygenation and an apprecia-tion of factors which may affect the reliability of samples
Arterial blood sampling is the gold standard however indwelling arterial catheters and arterial stab samples are usually restricted to infants who are critically ill or those who require sig-nificant ongoing intervention Gases are most frequently measured in capillary or venous samples which correlate well with arterial samples for PaCO2 pH and base excess in babies and children receiving intensive care These correlations however are not valid in infants with peripheral vasoconstriction and hypotension2324
Non-invasive monitoring techniques may enable us to reduce the frequency of blood gas sampling Transcutaneous monitoring
5 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
A systematic approach to blood gas analysis
1 Collect the relevant information
bull type of gas ndash capillary or arterial
bull Current respiratory support ndash document level
bull transcutaneous Co2 and Sao2 levels
bull Clarify no significant clinical events before sampling
2 pH accept a range between 730 and 745 in newborn
babies this is lower than in older children is there an
alkalosis (pH gt 745) or an acidosis (lt 730)
3 Co2 aim for a range between 45 and 65 kpa a paCo2 level
more than 65 kpa suggests inadequate alveolar ventilation
while less than 45 kpa suggests hyperventilation Correlate
values with non-invasive measures
4 o2 Can only be assessed from arterial gases aim for pao2
between 60 and 80 kpa Correlate results with pulse
oximetry levels
5 HCo3 and base excess normal HCo3 level is between 20 and
24 mmollitre and bases excess +3 to minus3
6 anion gap look at the anion gap and lactate to help identify
the cause of an acidosis normal lactate levels should be less
than 2 mmollitre
7 Respiratory or metabolic compensation look at the pH and
assess whether it is appropriate for the Co2 level or is there
evidence of compensation
8 interpret use both the clinical history and blood gas
findings to help you identify the primary problem aim your
management at treating the underlying cause
9 Reassess if clinical management changes have been made
repeat the blood gas after an appropriate time interval to
ensure improvement
Table 2
provides a highly accurate and reliable method for measuring PaCO2 through the skin it can however be technically difficult may cause tissue damage and is of limited reliability when peripheral perfusion is reduced25 Continuous end-tidal CO2 measurements correlate well with arterial CO2 values in patients with normal ventilation and perfusion however in babies with lung disease alveolar collapse small tidal volumes and rapid respiratory rates can make these measurements unreliable26 Despite its limitations transcutaneous monitoring provides the best method for CO2 trend monitoring in the neonatal intensive care unit (NICU)25
Oxygen saturation levels can be continuously measured non-invasively using pulse oximetry While oximetry is easy to perform and accurate on occasion SaO2 levels obtained may be unreliable when tissue perfusion is poor or with movement artefact SaO2 monitoring is highly sensitive at detecting hypoxia but is limited in detecting hyperoxia as at levels more than 90 small changes in SaO2 may result in unacceptably large increases in PaO227 It is therefore essential that SaO2 alarm limits are set for all neonates receiving respiratory support to detect hypoxia and prevent hyperoxia1627
Continuous non-invasive monitoring provides invaluable information when managing complex infants in the NICU but it does not replace the need for regular blood gas analysis
paeDiatRiCS anD CHilD HealtH 184 17
ReFeRenCeS
1 Kellum Ja Determinants of blood pH in health and disease
Crit Care 2000 4 6ndash14
2 Quigley R Baum m neonatal acid base balance and disturbances
Semin Perinatol 2004 28 97ndash102
3 Brouillette Rt Waxman DH evaluation of the newbornrsquos blood gas
status Clin Chem 1997 43 215ndash221
4 Chan JC acid-base disorders and the kidney Adv Pediatr 1983 30
401ndash471
5 Siggaard-andersen o the pH-log pCo2 blood acidndashbase nomogram
revised Scand J Lab Invest 1962 14 598ndash604
6 Saetta m mortola Jp interaction of hypoxic and hypercapnic stimuli
on breathing pattern in the newborn rat J Appl Physiol 1987 62
506ndash512
7 Baum m Quigley R postnatal renal development in Seldin DW
giebisch g eds the kidney physiology and pathophysiology new
york lippincott Williams and Wilkins 2000 p 703ndash726
8 ortiz la Quan a Weinberg a et al effect of prenatal
dexamethasone on rat renal development Kidney Int 2001 59
1663ndash1669
9 gabow pa Kaehny WD Fennessey pV goodman Si gross pa
Schrier RW Diagnostic importance of an increased serum anion gap
N Engl J Med 1980 303 854ndash858
10 lorenz Jm Kleinman li markarian K oliver m Fernandez J Serum
anion gap in the differential diagnosis of metabolic acidosis in
critically ill newborns J Pediatr 1999 135 751ndash755
11 Deshpande Sa platt mp association between blood lactate and
acid-base status and mortality in ventilated babies Arch Dis Child
1997 76 F15ndash20
12 Stewart pa modern quantitative acid-base chemistry Can J Physiol
Pharmacol 1983 61 1444ndash1461
13 Dakshinamurti S pathophysiologic mechanisms of persistent
pulmonary hypertension of the newborn Pediatr Pulmonol 2005
39 492ndash503
14 mourani pm ivy DD gao D abman SH pulmonary vascular
effects of inhaled nitric oxide and oxygen tension in
bronchopulmonary dysplasia Am J Respir Crit Care Med 2004
170 1006ndash1013
15 Deulofeut R Critz a adams-Chapman i Sola a avoiding hyperoxia
in infants le 1250 g is associated with improved short- and long-
term outcomes J Perinatol 2006 26 700ndash705
16 Chow lC Wright KW Sola a Can changes in clinical practice
decrease the incidence of severe retinopathy of prematurity in very
low birth weight infants Pediatrics 2003 111 339ndash345
17 Boylan gB young K panerai RB Rennie Jm evans DH Dynamic
cerebral autoregulation in sick newborn infants Pediatr Res 2000
48 12ndash17
18 Kaiser JR gauss CH pont mm Williams DK Hypercapnia during
the first 3 days of life is associated with severe intraventricular
hemorrhage in very low birth weight infants J Perinatol 2006 26
279ndash285
19 Fabres J Carlo Wa phillips V Howard g ambalavanan n Both
extremes of arterial carbon dioxide pressure and the magnitude of
fluctuations in arterial carbon dioxide pressure are associated with
severe intraventricular hemorrhage in preterm infants Pediatrics
2007 119 299ndash305
20 thome uH Carroll W Wu tJ et al outcome of extremely preterm
infants randomized at birth to different paCo2 targets during the
first seven days of life Biol Neonate 2006 90 218ndash225
6 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
21 Carlo Wa Stark aR Wright ll et al minimal ventilation to prevent
bronchopulmonary dysplasia in extremely-low-birth-weight infants
J Pediatr 2002 141 370ndash374
22 okumura a Hayakawa F Kato t et al Hypocarbia in preterm
infants with periventricular leukomalacia the relation between
hypocarbia and mechanical ventilation Pediatrics 2001 107
469ndash475
23 peters o Ryan S matthew l Cheng K lunn J Randomised
controlled trial of acetate in preterm neonates receiving parenteral
nutrition Arch Dis Child 1997 77 F12ndash15
24 yildizda D yapiciolu H yilmaz Hl Sertdemir y Correlation of
simultaneously obtained capillary venous and arterial blood gases
of patients in a paediatric intensive care unit Arch Dis Child 2004
89 176ndash180
25 aliwalas ll noble l nesbitt K et al agreement of carbon
dioxide levels measured by arterial transcutaneous and end tidal
methods in preterm infants 28 weeks gestation J Perinatol 2005
25 26ndash29
26 Hagerty JJ Kleinman me Zurakowski D et al accuracy of a new
low-flow sidestream capnography technology in newborns a pilot
study J Perinatol 2002 22 219ndash225
paeDiatRiCS anD CHilD HealtH 184 17
27 poets CF Wilken m Seidenberg J Southall Dp von der Hardt H
Reliability of a pulse oximeter in the detection of hyperoxemia
J Pediatr 1993 122 87ndash90
Practice points
bull a stable extracellular pH is important for optimal cellular
functioning
bull abnormalities in acidndashbase balance are regulated by buffer
systems and the respiratory and renal tract
bull maintaining a stable pH is challenging for newborn babies
due to their high rates of acid production and immature
regulatory mechanisms
bull arterial or capillary blood gases provide an effective way to
monitor acidndashbase balance in newborns
bull Blood gases should be analysed in a structured manner
assessing pH and then respiratory and metabolic components
bull the treatment of acidndashbase abnormalities should be directed
at the underlying problem not merely at correcting pH
7 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Recognition and management of neonatal seizuresmalcolm levene
AbstractSeizures are the most common major manifestation of central nervous
system dysfunction in the newborn there are many causes but perina-
tal asphyxia and haemorrhagicinfarction lesions account for about 75
there is now considerable evidence that frequent but short seizures in
the neonate affect subsequent neurodevelopmental outcome Studies
using eeg or modified continuous tracing of eeg activity (aeeg or CFm)
have shown that there is often electroconvulsive dissociation this re-
fers to poor correlation between electrical seizures and clinical seizures
Commonly used anticonvulsants appear to increase electroconvulsive
dissociation effective management of neonatal seizures has proved very
disappointing and less than 50 of seizures are abolished by first-line
anticonvulsant medication (phenobarbitone or phenytoin) Drugs such
as midazolam and lidocaine may further reduce seizures but require
more evaluation the challenge is to assess new and more effective anti-
convulsants which are themselves associated with little neurotoxicity
Keywords antiepileptic drugs eeg neonatal seizures neurodegeneration
Convulsions are the most common major neurological sign seen in newborn infants and their incidence estimated from large population studies is 26 per 1000 live births1 Premature infants are over four times more likely to have convulsions than full-term infants12 Neonatal status epilepticus (continuous seizure activity lasting 30 min or more) diagnosed clinically is rare and accounts for only 5 of infants with seizures1 although this is now recognized more frequently as the result of continuous EEG monitoring3
Neonatal convulsions are described as presenting in a num-ber of different ways and various seizure types can be seen in the same baby over a number of hours The frequencies of the various patterns of seizure activity are given in Table 1 In very premature babies and to a lesser extent in term infants minor movement abnormalities may be difficult to identify as subtle seizures These include lip smacking tongue thrusting mouth-ing pedalling type movements of the lower limbs or swimming movements of the arms Apnoea can be a common manifesta-tion of subtle seizures The signs can be protean and vary from baby to baby or even in the same baby Virtually any stereotypic
Malcolm Levene MD FMedSc FRCPCH FRCH is Professor and Head of
Department of Paediatrics and Child Health at University of Leeds Leeds
and Honorary Neonatologist at Leeds General Infirmary Leeds UK
paeDiatRiCS anD CHilD HealtH 184 178
movement may be a manifestation of a seizure disorder in the newborn
Aetiology
The more carefully the fitting baby is investigated the more likely it is that a cause for the seizures will be found A number of recent papers have described the aetiology of neonatal con-vulsions after extensive investigations14 Tekgul et al4 recently studied a consecutive group of full-term infants with evidence of neonatal convulsions (recognized both clinically and on EEG) and reported their outcome Table 2 summarizes these data as well as risk of moderate or severe disability for each causative factor Perinatal asphyxia is the commonest cause for convul-sions in term infants with haemorrhagic or ischaemic lesions also being common
Overall the prognosis for the group of term babies with con-vulsions was good 72 had a favourable outcome Where asphyxia (hypoxicndashischaemic insult) is the cause of neonatal convulsions the outcome is poor in 50 The prognosis for neonatal convulsions when they were due to arterial or cere-brovenous infarction or intracranial haemorrhage was generally good Individually inborn errors are a very rare cause of neo-natal convulsions but in view of the treatable nature of some of these it is essential that these be considered and investigated appropriately5
Patterns of seizure activity in the newborn
Movement pattern Frequency ()
Clonic 50
tonic 20
Subtle 10ndash35 depending on maturity
myoclonic 5
Table 1
Cause incidence and outcome of neonatal convulsions in term infants14
Aetiological factor Incidence () Poor outcome ()
asphyxia 38ndash40 50
Cerebral arteriovenous
infarction
20 0
intracranial haemorrhage 12ndash20 13
Congenital cerebral anomaly 5ndash10 100
Hypoglycaemiahypocalcaemia 3ndash19
infection 3ndash20
inborn error of metabolism 1
unknown cause 10ndash13 0
Refers to moderate and severe neurodevelopmental abnormalitynumbers too small to make meaningful predictions
Table 2
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Controversies in the clinical management of neonatal seizures
In recent years we have learnt much more about the neurobi-ology of seizures and their effect on the developing brain The neonatal brain is in a neurophysiologically hyperexcitable state compared to the more mature brain and therefore is more prone to seizure activity This is due largely to a relative excess of GABA neuroreceptors GABA receptors are usually inhibitory but in the immature brain they have a paradoxically excitatory effect This changes at about term in primates and with progressive develop-ment they adopt a neuroinhibitory role6
The propensity to seizures in the neonatal brain makes resolv-ing the balance of risks between continuing seizure activity on the one hand against potentially adverse effects of therapy on the other a very important equation Added to this is the problem of accurately diagnosing neonatal seizures and whether commonly used anticonvulsants are successful in controlling them
These conundrums can be posed as a series of challenging questions which are discussed below
Do neonatal convulsions cause brain injuryConvulsions are a sign of neurological compromise and may indi-cate significant underlying structural brain damage or biochemi-cal disturbance which may cause further brain damage in its own right There has been considerable debate about the scale of the disability that convulsions cause the immature brain over and above that due to the underlying cause Most of our knowledge comes from studies in rodents and these have provided some tentative answers to this question
Seizures in the mature brain lead to neuronal necrosis but studies in very young rat pups whose brain development is somewhat similar to full-term infants have shown that a series of five brief seizures on five successive days does not cause struc-tural neuronal damage but does produce morphological changes in hippocampal neurones and worryingly deficits in the rat learning and visual spatial memory function in adolescent and adult life7 A single prolonged neonatal convulsion in similarly immature rats does not produce any functional effects8 Others have shown that following priming of the neonatal rat brain by short seizures as described above a further insult comprising induction of status epilepticus in the same rats at an older age causes neuronal necrosis9 This has been referred to as the lsquotwo hit hypothesisrsquo10
A more specific question is does seizure activity in an already significantly compromised brain cause additional neuropathol-ogy Wirrell et al11 studied a series of immature rat pups with the induction of an hypoxicndashischaemic (asphyxial) insult fol-lowed by either chemically-induced fits or a control sham pro-cedure In the more severely asphyxiated animals the degree of brain damage was increased significantly in those that had the additional burden of induced seizures
In summary these studies show that the immature brain is more resistant to short frequent post-seizure damage than the mature brain but despite resulting in no loss of neuronal numbers the function of the brain is permanently affected in later life In the asphyxiated brain seizures appear to have an additional adverse effect on brain damage Furthermore the immature brain that has been lsquoprimedrsquo by early seizures is more
paeDiatRiCS anD CHilD HealtH 184 179
vulnerable to status epilepticus later in life It would appear from these data that frequent seizures in the human infant should be stopped and this begs the question as to whether currently used anticonvulsants effectively control neonatal seizures
Can we rely on clinical versus EEG diagnosis of neonatal convulsionsTraditionally the diagnosis of neonatal convulsions has been made by observation and description of the frequency of abnor-mal movements EEG has been technically difficult in the hostile electrical activity of a neonatal intensive care environment and considerable expertise is required for analysis of the trace It is usually not practical to undertake traditional EEG recordings at the time the baby shows abnormal movements More recently various technological developments have allowed more direct investigation of neuronal electrical activity by either video-EEG or compressed recording of the amplitude integrated EEG (aEEG or CFM)
Rennie et al3 at Kingrsquos College Hospital London have under-taken extensive evaluation of video-EEG and have found that this technique detects many convulsions not recognized by a single channel aEEG or CFM trace Of 19 infants with evidence of convulsions on EEG only four were recognized on CFM but this may have been due to the observersrsquo lack of experi-ence with this technique In other centres that have developed appropriate expertise aEEG or CFM has proved more sensitive to the detection of seizures Video-EEG studies have also shown that many movements interpreted by experienced clinicians to be seizures are not associated with abnormal cortical activity Conversely many electrical seizures are not associated with abnormal movements This is referred to as electroconvulsive dissociation
In summary clinical observation alone to detect the fitting baby is unreliable in that it may either over-detect seizure activ-ity which is not present on EEG or under-detect clinical seizures in infants with EEG-proven convulsions The decision as to which babies to treat with antiepileptic drugs therefore becomes somewhat arbitrary
Do anticonvulsants stop neonatal seizuresAlthough neonatal seizures are common there are few random-ized controlled trials assessing the benefits of antiepileptic drugs (AEDs) in the treatment of this condition Phenobarbitone is the most widely used first-line AED and in an Australasian study 95 of neonatologists and paediatric neurologists used this drug as first-line management12 The most commonly used loading dosage is 20 mgkg but regimens of up to 40 mgkg have been recommended (Table 3)13 Four trials have evaluated the effect of phenobarbitone in abolishing neonatal seizures Two of these studies used EEG to monitor response to the drug1415 and one compared phenobarbitone with phenytoin15 In the latter study seizures were completely controlled in only 43 of babies and in the group where phenytoin was the first drug used com-plete seizure control was achieved in 45 This study switched babies from their first AED to the other if complete control was not obtained on EEG monitoring after exposure to first-line therapy In babies who had been given phenobarbitone as first-line therapy seizure control was only achieved in 57 after phenytoin was added In those given phenytoin first complete
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Dosage regimens for first- second- and third-line anticonvulsants in the neonatal period
Loading dose Second loading dose if first
unsuccessfulMaintenance dose
phenobarbitone 20 mgkg by slow iv injection 10 mgkg iv 25ndash5 mgkg od
phenytoin 20 mgkg iv over 20 min not recommended
midazolam 150ndash200 μgkg iv infusion 1 μgkgmin iv infusion increasing to 5 μgkgmin
until favourable response
lidocaine 2 mgkg iv over 10 min 6 mgkgh for 6 h iv then 4 mgkgh for 12 h then
2 mgkgh for 12 h
lorazepam 005ndash01 mgkg by slow iv injection
Diazepam 03ndash04 mgkg iv over 3ndash5 min
lidocaine should not be used if the infant has previously been treated with phenytoin
Table 3
seizure control was achieved with the adding of phenobarbitone in 62
Boylan et al14 assessed the efficacy of phenobarbitone (20ndash40 mgkg iv over 20 min) in 14 babies monitored by video-EEG in only four was there complete abolition of seizures and in the other 10 electroconvulsive seizure activity increased whereas clinical evidence of seizures reduced This has been termed elec-troclinical dissociation and anticonvulsant drug use in the new-born appears to increase this feature They also showed that the babies least likely to respond to the first-line AED are those with the most abnormal background EEG
Two studies have evaluated the use of phenobarbitone in babies who had sustained significant asphyxial insult at birth Hall et al13 compared high-dose phenobarbitone (mean 39 mgkg) versus standard dose (27 mgkg) and reported fewer convul-sions and a significant reduction of severe disability or death in the high dose group (RR 030 CI 010ndash093) A recent study from India16 of babies with hypoxicndashischaemic encephalopathy ran-domized 25 babies to phenobarbitone (20 mgkg loading dose) and compared them with 20 control babies Only 2 of 25 (4) in the phenobarbitone group developed convulsions compared with 8 of 20 (40) in the control group (p = 001) Because of the specific enrolment criteria (asphyxial insult) neither of these studies is strictly comparable to the studies by Painter et al15 and Boylan et al14 whose intention was to assess the efficacy of first-line anticonvulsant therapy on convulsions of any cause diagnosed either clinically or by EEG
Other anticonvulsants used as second- and third-line drugs have been subject to few studies in the newborn Midazolam is administered as a bolus followed by continuous infusion A recent study17 has shown that in 10 of 13 neonates given intravenous midazolam for status epilepticus control of electri-cal seizures was achieved within the first hour of treatment having been previously shown to be refractory to phenobarbi-tone treatment Some of these babies required a second bolus infusion of midazolam to obtain control of all electrographic seizures
In some parts of Europe lidocaine is used as a third-line anti-convulsant Malingre et al18 evaluated 20 infants refractory to
paeDiatRiCS anD CHilD HealtH 184 180
both phenobarbitone and midazolam and who were then given lidocaine by continuous infusion Lidocaine was effective in abolishing electroconvulsive seizures diagnosed by aEEG in 76 of the treatment courses studied No babies developed cardiac arrhythmias a previously reported complication of lidocaine in older patients As a result of pharmacokinetic studies the dosage regimen has been modified (see Table 3)
In summary phenobarbitone is effective in seizure control in less than 50 of babies and even when combined with phe-nytoin the efficacy of these drugs together remains poor More worrying is the observation that phenobarbitone tends to reduce clinically evident seizures thereby giving the clinician a false sense of security whilst having little or no effect on the num-bers of electroconvulsive disorders This has been summarized appropriately as lsquoafter all these years we still love what doesnrsquot workrsquo19 Both midazolam and lidocaine infusions appear to be effective in abolishing severe seizures in some infants resistant to phenobarbitone Lidocaine should not be given to babies previ-ously exposed to phenytoin for fear of a synergistic adverse effect on cardiac rhythm
Do antiepileptic drugs cause brain damageA riskndashbenefit analysis is needed to evaluate the efficacy of anticonvulsants in stopping neonatal seizures which is poor with standard anticonvulsants as discussed above against the risk of administering the anticonvulsant drugs themselves Phenobarbitone has been reported to have adverse effects on the developing brain including inhibition of brain growth20 neuronal toxicity21 and adverse behavioural and cognitive effects into adult life when administered to young animals22 Phenytoin shows unpredictable plasma levels and potential cardiotoxicity
Recent studies have shown an effect of AED exposure on the developing brain by causing neurodegeneration23 Phenytoin administration to immature rat pups at doses which produce serum levels similar to those achieved in human neonates was associated with widespread neuronal death as a result of apop-tosis (programmed cell death) Phenobarbitone had a similar effect when a dosage regimen similar to 40 mgkg was used and
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
this effect was maximal in the more immature brain Diazepam and clonazepam also resulted in a similar effect Midazolam and lidocaine were not tested in this study The combination of phenobarbitone or phenytoin with diazepam had a particularly profound effect on neurodegeneration
In summary recent data suggest that the commonly used AEDs for neonatal convulsions may in themselves cause neuro-degeneration due to apoptosis with lasting effects on develop-ment Many babies with neonatal convulsions are treated with at least two AEDs and this may produce more severe adverse effects than the seizures themselves
Practical management of neonatal seizures
Assimilation of these data and formulation of a rational policy is difficult when faced with a fitting neonate on an intensive care unit and pressure on the medical staff to lsquodo somethingrsquo but it is important to accept that sometimes doing nothing is preferable to using potentially dangerous drugs in a situation which does not warrant such intervention Many babies who have normal interseizure neurological clinical findings and whose seizures are relatively brief and infrequent probably do not need anticon-vulsant medication A normal or near-normal background EEG trace should reassure the clinician that anticonvulsants can be withheld
Some causes of neonatal convulsions are treatable such as meningitis hypoglycaemia hypocalcaemia and inborn errors of metabolism and each baby should be rapidly and carefully investigated for cause of the convulsions
In some babies clinical assessment of seizures is difficult ie when the baby is very sick small or paralyzed Sometimes it may be difficult to assess the significance of certain movement pat-terns Under these circumstances an EEG may prove to be very helpful In many units EEG is not available out of hours and a simple aEEG or CFM is strongly advised Modern instruments are very simple to apply and prolonged or frequent seizures should be identified with only moderate training The printout can be faxed to a more senior doctor if there is doubt as to what is shown on the trace
The balance of knowledge now is that frequent seizures cause additional damage to the developing brain and that treatment to abolish the seizures is warranted Unfortunately there is little evidence that the majority of seizures can be effectively termi-nated by current standard therapy Furthermore it appears that the more abnormal the background EEG the more difficult it is to control the seizures Nevertheless a written protocol for the management of neonatal convulsions is required on each unit Phenobarbitone and phenytoin remain the mainstay of treat-ment although their effectiveness is disappointing There is little to suggest that midazolam is more effective than lidocaine as third-line therapy but lidocaine is precluded if phenytoin has been previously used
In view of the anxiety as to the neurodegenerative effects on the immature brain of most anticonvulsants used in the neonatal period (particularly when multiple drugs are used) it is prefer-able to use only one drug to maximum dosage before introduc-ing a second In addition the duration of anticonvulsants should be minimized and the drugs stopped at the earliest opportu-nity It is my practice to stop anticonvulsants prior to discharge
paeDiatRiCS anD CHilD HealtH 184 18
from hospital if the baby is neurologically normal on clinical examination
REFEREnCES
1 Ronen gm penney S andrews W the epidemiology of clinical
neonatal seizures in newfoundland a population-based study
J Pediatr 1999 134 71ndash75
2 lanska mJ lanska DJ Baumann RJ et al a population-based study
of neonatal seizures in Fayette County Kentucky Neurology 1995
45 724ndash732
3 Rennie Jm Chorley g Boylan gB et al non-expert use of the
cerebral function monitor for neonatal seizure detection Arch Dis
Child Fetal Neonatal Ed 2004 89 F37ndashF40
4 tekgul H gauvreau K Soul J et al the current etoliologic profile
and neurodevelopmental outcome of seizures in term newborn
infants Pediatrics 2006 117 1270ndash1280
5 Surtees R Wolf n treatable neonatal epilepsy Arch Dis Child 2007
92 659ndash661
6 Ben-ari y Holmes gl effects of seizures on developmental
processes in the immature brain Lancet Neurol 2006 5 1055ndash
1063
7 Holmes gl gairsa Jl Chevassus-au-louis n et al Consequences of
neonatal seizures in the rat morphological and behavioral effects
Ann Neurol 1998 44 845ndash857
8 Stafstrom Ce Chronopoulos a thurber S et al age-dependent
cognitive and behavioural deficits following kainic-acid inducing
seizures Epilepsia 1993 34 420ndash432
9 Schmid R tandon p Stafstrom Ce et al effects of neonatal seizures
on subsequent seizure-induced brain injury Neurology 1999 53
1754ndash1761
10 Hoffmann aF Zhao Q Holmes gl Cognitive impairment following
status epilepticus and recurrent seizures during early development
support for the ldquotwo-hit hypothesisrdquo Epilepsy Behav 2004 5
873ndash877
11 Wirrell eC armstrong ea osman lD et al prolonged seizures
exacerbate perinatal hypoxic-ischemic brain damage Pediatr Res
2001 50 445ndash454
12 Carmo KB Barr p Drug treatment of neonatal seizures by
neonatologists and paediatric neurologists J Paediatr Child Health
2005 41 313ndash316
13 Hall Rt Hall FK Daily DK High-dose phenobarbital therapy in term
newborn infants with severe perinatal asphyxia a randomized
prospective study with three-year follow-up J Pediatr 1998 132
345ndash348
14 Boylan gB Rennie Jm pressler Rm et al phenobarbitone neonatal
seizures and video-eeg Arch Dis Child Fetal Neonatal Ed 2002 86
F165ndash170
15 painter mJ Scher mS Stein aD et al phenobarbital compared with
phenytoin for the treatment of neonatal seizures N Engl J Med
1999 341 485ndash489
16 Singh D Kumar p narang a a randomized controlled trial of
phenobarbital in neonates with hypoxic ischemic encephalopathy
J Matern Fetal Neonatal Med 2005 18 391ndash395
17 Castro Conde JR Borges H Domenech martinez e et al midazolam
in neonatal seizures with no response to phenobarbital Neurology
2005 64 876ndash879
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
18 malingre mm Van Rooij lgm Rademaker Cma et al Development
of an optimal lidocaine infusion strategy for neonatal seizures Eur
J Pediatr 2006 165 598ndash604
19 Sankar R painter mJ neonatal seizures after all these years we still
love what doesnrsquot work Neurology 2005 64 776ndash777
20 Diaz J Schain J Bailey Bg phenobarbital-induced brain growth
retardation in artificially reared rat pups Biol Neonate 1977 32 77ndash82
21 mattson RH phenobarbital toxicity in levy RH Dreifuss Fe
mattson RH et al eds antiepipeptic Drugs 3rd edn new york
Raven 1985 p 341ndash355
22 mikati ma Holmes gl Chronopoulos a et al phenobarbital
modifies seizure-related brain injury in the developing brain Ann
Neurol 1994 36 425ndash453
23 Bittigau p Sifringer m genz K et al antiepileptic drugs and
apoptotic neurodegeneration in the developing brain Proc Natl
Acad Sci U S A 2002 99 15089ndash15094
paeDiatRiCS anD CHilD HealtH 184 182
Practice points
bull the clinician needs to be aware that almost any repetitive
stereotype movement pattern can be a manifestation of
neonatal seizures
bull eeg is important in defining neonatal seizures
bull Frequent short-lived seizures have been shown to cause long-
term neurodevelopmental problems
bull Conventional anticonvulsant medication is ineffective in
abolishing neonatal seizures in greater than 50 of cases
bull there is evidence that exposure of the neonatal brain to
multiple anticonvulsants causes neuronal death
bull Future research is needed to evaluate more effective
anticonvulsants for treating this condition
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
Emotional support for families of sick neonatesMarina nicolaou
cristine Glazebrook
AbstractParents of sick neonates experience high levels of stress anxiety and
depression Most interventions with families of sick infants have focused
on fostering the motherndashinfant relationship through the provision of
information about infant developmental needs or through increased
motherndashinfant contact Many of these studies have reported improved
maternal well-being though there are some concerns about the scope
and practicality of large-scale interventions The few studies to have
prioritized emotional support for parents of sick neonates have pro-
duced encouraging results even interventions requiring relatively few re-
sources such as telephone support parent-to-parent support and group
support have been associated with reduced psychological morbidity for
parents The needs of parents can change throughout their infantrsquos hos-
pitalization and not all want or benefit from the provision of additional
support Thus neonatal intensive care units should aim to provide a
varied flexible and sustainable programme of support options Further
research should focus on the needs of fathers
Keywords mental health neonatal intensive care parents
The admission of an infant to neonatal care is acknowledged to be a source of considerable distress for families This review aims to explore evidence for the psychological impact on families of having an infant in neonatal intensive care and to identify evi-dence for the effectiveness of interventions to promote parental well-being It will conclude with recommendations for strategies to support parents of vulnerable infants and suggestions for fur-ther research
Psychological impact of neonatal care for parents
The majority of research examining the effect on parents of having a sick neonate has focused on families of premature or low birthweight infants Such research has found that parents with a sick neonate exhibit high levels of stress compared to normative samples and to parents of healthy full-term infants1 Singer et al2 examined the stress experienced by mothers of high-risk very low birthweight (VLBW) low-risk VLBW and term
Marina Nicolaou MPhil is a Teaching Assistant at the School of
Community Health Sciences University of Nottingham Nottingham UK
Cristine Glazebrook PhD is a Professor of Health Psychology at the School
of Community Health Sciences University of Nottingham Nottingham UK
PaeDiaTrics anD cHilD HealTH 184 196
infants Several self-report measures were used including the Brief Symptom Inventory the Parenting Stress Index (PSI) the Impact on Family Scale and the Family Inventory of Life Events and Changes (FILE) Mothers of VLBW infants had more psycho-logical distress at 1 month compared to mothers of term infants Mothers of high-risk VLBW infants also reported high psycho-logical distress at 2 years and high levels of parenting stress at 3 years Mothers have also been found to have higher stress levels compared to fathers Shaw et al3 examined the prevalence of acute stress disorder (ASD) in 40 parents whose infants were in the neonatal intensive care unit (NICU) Nearly half of the moth-ers (44) met the criteria for ASD although none of the fathers did Furthermore the severity of the symptoms (measured by the number of concurrent symptoms) was greater for the moth-ers than for the fathers3 The reasons behind this difference have been widely speculated with some believing that it is due to the mothersrsquo greater psychological involvement with the infant as evidenced by their general greater vulnerability to postpartum psychological disorder It could also reflect gender differences in coping style
Having an infant who requires intensive medical care repre-sents a significant emotional burden for families Not only is there extreme anxiety surrounding the infantrsquos health and distress for the childrsquos suffering there is also the unfamiliar and intimidating environment of the NICU to adjust to Hopper in her review of the literature identified sources of stress for parents of sick neo-nates as falling into three areas4 Situational factors included the severity of the infantrsquos illness and how parents adapted to the life crisis of having a sick infant Personal factors involved parental emotions about their roles and the instrumental and informa-tional support which were available to them The third area was classified as environmental sources of stress and included the environment of the NICU and the relationship between parents and members of staff This relationship has been examined by several studies in the nursing literature nurses are seen as ide-ally placed to provide the necessary support and information to parents with sick neonates However whilst some studies have shown that supportive and helpful hospital staff can have a posi-tive effect on parents other studies have highlighted the prob-lems and difficulties which can manifest It has been shown that parents and nurses often have very different ideas about issues eg the necessary skills and competencies needed in an NICU or the characteristics that make a lsquogood motherrsquo
Research has shown that there may be a relationship between high levels of parental stress and an increased likelihood of depression5 Postpartum depression is a psychiatric illness which appears in 10ndash15 of postpartum women Its reported preva-lence rates however have ranged from less than 10 up to 306 depending on the instruments used the population exam-ined and the timing of the research Several factors have been found to be associated with postpartum depression including poor social support and infant-related stressors6 Evidence indi-cates that postnatal depression may be underreported and this is of concern since the mental and psychological health of the mother can affect her relationship with her infant and thus the infantrsquos cognitive and emotional development5 Depressed moth-ers appear to look touch and talk to their infants less frequently and also appear to show fewer positive and more negative faces7 The vocalizations of mothers suffering with depression have also
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
been found to be less effective at promoting cognitive growth and learning in infants8
If researchers are interested in finding ways of providing sup-port for families of sick neonates then they must listen to what such families perceive their needs to be in order to avoid increas-ing anxiety and distress Furthermore the provision of appropri-ate support be it emotional informational or social will enhance parental coping abilities increase self-esteem and reduce anxiety It should be noted though that the research conducted around these issues has often taken lsquosupport needsrsquo as being synony-mous with lsquoinformation needsrsquo Such studies have examined the type the amount and quality of information that parents receive and perceive themselves as needing but have not explored in equal depth the perceived emotional support needs of families who have a sick infant In addition the needs of parents may change throughout their infantrsquos illness Ward examined the per-ceived needs of 52 parents of infants in an NICU9 Parents rated the needs of their hospitalized infant as most important along with the need to be reassured Interestingly they ranked their support needs as least important This research was conducted during the first week of the infantsrsquo hospitalization however which would explain the preoccupation of the parents with the infantrsquos health These results demonstrate that if researchers want to find ways of providing emotional support to parents of sick neonates they must be prepared not only to listen to parents but also to be flexible enough to satisfy the parentsrsquo changing needs and expectations
Interventions aimed at supporting parents
Most interventions that been evaluated in controlled studies have focused on supporting the motherndashinfant relationship and provid-ing information on infant development Many of these interven-tions have included the aim of improving the parental emotional state and thus psychological outcomes such as stress or anxi-ety have been assessed However few studies appear to include fathers This means that strategies implemented to provide emo-tional support to families of sick neonates are often derived from interventions tailored for mothers even though fathers may have different emotional needs
A wide range of interventions with mothers and infants has been evaluated in the NICU Increasing motherndashinfant contact through kangaroo care has been found to reduce maternal anxiety1011 and educational programmes delivered to fami-lies in the NICU have also been associated with reduced emo-tional difficulties in parents12ndash14 Kaaresen and colleagues implemented an intervention which consisted of eight sessions before discharge and four home visits all by trained nurses The sample included 71 premature infants in the intervention group 69 premature infants in the control group and 74 infants in the full-term control group The randomized controlled trial found that the intervention reduced parenting stress in both mothers and fathers of premature infants compared to controls to a level equivalent to parents in the term control group13 At 6 months corrected age mothers of preterm infants who had not received the intervention had total PSI scores which were 17 points higher than the mothers of infants born at term (an effect size of 057) A similar study evaluated the efficacy of an educationalndashbehavioural programmendashCreating Opportunities for
PaeDiaTrics anD cHilD HealTH 184 19
Parent Empowerment (COPE) ndash through a randomized controlled trial with 260 families of premature infants14 COPE was a four-phase educationalndashbehavioural programme which began as early as 2ndash4 d after mothers had given birth and continued until 1 week after discharge from the NICU The programme consisted of audiotaped and written infant behaviour information along with photographs which focused on common behaviours and characteristics of premature infants It also included various par-ent activities in the form of a four-phase workbook which aimed to assist mothers in the implementation of the experimental infor-mation COPE was found significantly to reduce maternal stress in the NICU as well as maternal anxiety and depressive symptoms after hospitalization In contrast a cluster randomized trial of a parenting intervention delivered to mothers of very premature infants from soon after birth showed no benefits for parenting stress1 The authors hypothesized that the intervention had not been of sufficient intensity particularly in the weeks surrounding discharge Neonatal care presents a significant barrier to parent-ing in the early weeks following a very preterm birth and so inter-ventions which focus on the developmental needs of infants and the parentndashchild relationship should particularly aim to support parents as they take on the parenting role There was also concern that the intervention had failed to reach those most at risk
Since large-scale projects can be costly to implement and may often fail to reach the families in most need it may be wiser to focus on intervention programmes which are more practical and easier to implement within a neonatal care setting Research has shown that even interventions which are based on one-off meet-ings with parents of sick neonates can be effective Jotzo and Poets examined the effect of an intervention programme aimed at reducing the severity of traumatic responses as a result of giv-ing birth prematurely15 Their programme consisted of a one-off intervention meeting along with additional psychological help throughout the hospitalization of the infant The meeting cov-ered a variety of issues including a reconstruction of the events shortly before and after the infantrsquos birth relaxation techniques discussion of coping strategies available resources and social support and support during emotional outbursts The measures used included the Impact of Event Scale (IES) and the Peritrau-matic Dissociative Experience Questionnaire At discharge the mothers who received the intervention were found to have a significantly lower traumatic impact as a result of premature birth Furthermore fewer mothers in the intervention group showed symptoms of clinically significant psychological trauma at discharge compared to mothers in the control group (36 vs 76)15 The lsquoParents Circle Programrsquo is another intervention with a similar structure16 This consisted of a 90 min session for parents with the aim of enhancing the developing relationship between parents and infants and to offer parents support A total of 104 parents (59 mothers and 45 fathers) and 44 members of hospital staff were asked to evaluate the programme and their results were analysed using content analysis Families reported gaining perspective on their situation feeling supported becom-ing aware of cues and optimizing interactions and becoming aware of available resources Parents and staff alike felt that participating in the intervention helped parents overcome the difficulties associated with the early time of their infantrsquos hos-pitalization Additional studies have also found positive results with fairly minimal interventions including discussion groups
7 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
in the NICU music during kangaroo care and pairing mothers of sick neonates with trained mothers who had been through similar experiences
Parent support programmes
Parent support programmes (PSPs) which are based in NICUs can provide parents with the opportunity to talk to parents who have been in similar situations and also to discuss their emo-tions with professionals who can help them cope with their situa-tion111718 The parent-to-parent support programme for mothers of preterm infants evaluated by Preyde and Ardal included edu-cational parental support group meetings and individual par-ent-to-parent support (primarily telephone support)19 Measures used included the Parental Stressor Scale NICU the State and the Trait Anxiety Inventories and the Beck Depression Inven-tory After 4 months of participation mothers in the intervention group reported lower levels of stress state anxiety and depres-sion compared to control group mothers The authors speculated however that the participants who were able to meet face to face with other parents were those who benefited the most Hurst conducted a comprehensive survey of an NICU-based PSP This PSP was provided in a variety of formats including a weekly parent support group hospital visitation and 24-h telephone sup-port20 Of the 477 participants 303 families used the PSP dur-ing a 2-year evaluation period with 78 using only one form of support and 18 using two forms Of a sub-sample of 48 parents asked to complete an evaluation of the PSP 92 stated that they would recommend such a programme to other parents Furthermore the majority of parents felt that it made them feel supported and helped them deal with their emotions20 This is an indication that such programmes can be very successful in sup-porting parents throughout their infantrsquos hospitalization It also shows that it can be beneficial to give parents several options and formats when it comes to such support services It is impor-tant to consider though that both the Hurst and the Preyde and Ardal studies found that some participants did not find the sup-port programmes helpful even reporting that they had caused them increased stress and anxiety Therefore it should not be assumed that support programmes will suit every individual and will provide the required support for all parents1920 NICUs need to be flexible enough to provide parents with a range of forms of support to choose from
The increased understanding of the strains that parents of sick neonates have to deal with has also led to efforts to improve customary practices in NICUs Family-centred care focuses on infants and their needs and attempts to redefine the relationship between parents and caregivers These practices strive to provide parents with support during their infantrsquos illness by focusing on freely sharing information and on the collaboration between parents and hospital staff Family-centred care has been found to be associated with several beneficial outcomes including improved parental satisfaction increased parental comfort staff satisfaction and decreased parental stress18 Research is already examining these practices and questioning how these can be improved further Such research reflects the increasing effort focused on lsquohumanizingrsquo the environment in NICUs in order to make parents feel more comfortable about spending time with their infants
PaeDiaTrics anD cHilD HealTH 184 19
Conclusion
Surprisingly few interventions have prioritized the provision of emotional support for parents of sick neonates or accounted for the changing needs and wishes of parents over the course of their infantrsquos care Large-scale supportive education-based inter-ventions have been shown to be effective in reducing parental distress However the feasibility and sustainability of such pro-grammes should also be considered Programmes which require significant additional resources can be expensive and there are also issues of training and quality control Interventions which require significant input from parents may also place additional burdens on families making them potentially less accessible to those most at risk Arguably the aim should be to explore ways of providing acceptable and effective informational support which could be complemented by emotional support from health professionals and from other parents in the unit Increasingly studies are exploring the use of computers and multimedia as an engaging flexible and cost-effective method of targeting indi-vidual needs and providing support and information Such com-puter-based and interactive multimedia interventions have been found to be successful with a range of patient groups and could therefore be examined as a complementary method of providing informational support to families with sick neonates
REfEREnCEs
1 Glazebrook c Marlow n israel c et al randomised trial of a
parenting intervention during neonatal intensive care Arch Dis Child
Fetal Neonatal Ed 2007 92 F438ndash443
2 singer lT salvator a Guo s collin M lilien l Baley J Maternal
psychological distress and parenting stress after the birth of a very
low-birth-weight infant JAMA 1999 281 799ndash805
3 shaw rJ Deblois T ikuta l Ginzburg K Fleisher B Koopman c
acute stress disorder among parents of infants in the neonatal
intensive care nursery Psychosomatics 2006 47 206ndash212
4 Hopper a sources of stress for parents of a sick neonate a
literature review Pediatr Nurs 2000 30 29ndash32
5 Davis l edwards H Mohay H wollin J The impact of very
premature birth on the psychological health of mothers Early Hum
Dev 2003 73 61ndash70
6 Bernazzani O saucier J-F David H Borgeat F Psychosocial
predictors of depressive symptomatology level in postpartum
women J Affect Disord 1997 46 39ndash49
7 Field T infants of depressed mothers Infant Behav Dev 1995 18
1ndash13
8 Kaplan Ps Bachorowski J-a Zarlengo-strouse P child-directed
speech produced by mothers with symptoms of depression fails
to promote associative learning in 4-month-old infants Child Dev
1999 70 560ndash570
9 ward K Perceived needs of parents of critically ill infants in
a neonatal intensive care unit (nicU) Pediatr Nurs 2001 27
281ndash286
10 lai Hl chen cJ Peng Tc et al randomized controlled trial of music
during kangaroo care on maternal state anxiety and preterm infantsrsquo
responses Int J Nurs Stud 2006 43 139ndash146
8 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
11 Tallandini Ma scalembra c Kangaroo mother care and mother-
premature infant dyadic interaction Infant Ment Health J 2006 27
251ndash275
12 Ohgi s Fukuda M akiyama T Gima H effect of an early intervention
programme on low birthweight infants with cerebral injuries
J Paediatr Child Health 2004 40 689ndash695
13 Kaaresen Pi ronning Ja Ulvund se Dahl lB a randomized
controlled trial of the effectiveness of an early-intervention program
in reducing parenting stress after preterm birth Pediatrics 2006
118 e9ndash19
14 Melnyk BM Feinstein nF alpert-Gillis l et al reducing premature
infantsrsquo length of stay and improving parentsrsquo mental health
outcomes with the creating opportunities for parent empowerment
(cOPe) neonatal intensive care unit program a randomized
controlled trial Pediatrics 2006 118 e1414ndash1427
15 Jotzo M Poets cF Helping parents cope with the trauma of
premature birth an evaluation of a trauma-preventive psychological
intervention Pediatrics 2005 115 915ndash919
16 Pearson J andersen K evaluation of a program to promote positive
parenting in the neonatal intensive care unit Neonatal Netw 2001
20 43ndash48
17 roman l lindsay J Boger r et al Parent-to-parent support
initiated in the neonatal intensive care unit Res Nurs Health 1995
18 385ndash394
18 Meyer ec coll cTG lester BM Boukydis cFZ McDonough sM Oh w
Family-based intervention improves maternal psychological well-
being and feeding interaction of preterm infants Pediatrics 1994
93 241ndash246
PaeDiaTrics anD cHilD HealTH 184 19
19 Preyde M ardal F effectiveness of a parent ldquobuddyrdquo program for
mothers of very preterm infants in a neonatal intensive care unit
CMAJ 2003 168 969ndash973
20 Hurst i One size does not fit all Parentsrsquo evaluations of a support
program in a newborn intensive care nursery J Perinat Neonatal
Nurs 2006 20 252ndash261
Practice points
bull Parents of sick neonates experience significant distress and
exhibit higher levels of stress anxiety and depression than
parents of healthy infants
bull educational support emotional support and increased
motherndashinfant contact have been shown to promote maternal
well-being
bull emotional support for fathers has been largely neglected in
the research literature
bull Parents benefit from a choice of supportive facilities which
could include face-to-face sessions with health professionals
telephone support hospital visitation parent-to-parent
support and unit-based group support meetings
bull Parentsrsquo support needs can change during their infantrsquos
hospitalization and not all parents want or benefit from the
provision of additional information and emotional support in
the neonatal unit
9 copy 2008 elsevier ltd all rights reserved
Personal Practice
When should enteral feeds be started in preterm infantsnicholas D embleton
AbstractPaediatricians are regularly faced with the question of when best to start
enteral feeds in preterm infants this is important as longer term out-
come may be compromised by sub-optimal nutrition in early life clinical
factors that may affect the decision to start and the risk and benefits
are discussed
Keywords breast milk feeding nutrition parenteral nutrition
Key points in the history
Alice is lsquonutritionally vulnerablersquo and whilst this may not be immediately apparent it will affect her long term outcome Her energy stores are extremely limited and consist primarily of pro-tein She has less than 5 fat and little energy associated with stored glycogen She is losing about 1 gkgd protein equivalent so she needs at least that and a minimum of 50ndash60 kcalkg of energy just to maintain the status quo let alone grow
Her weight is on the 25th centile Review of any antenatal his-tory may reveal whether fetal growth was normal Fetal growth retardation can occur with a weight greater than 10th centile The presence of antenatal absent or reversed end diastolic flow in the umbilical artery indicates poor gut blood flow This increases the risk of necrotizing enterocolitis (NEC) and might suggest a more cautious approach to starting feeds1
She has no important cardiovascular problems but if she were hypotensive gut blood flow may be low There is no umbilical
Nicholas D Embleton BSC (Hons) MBBS (Hons) MD FRCPCH is Consultant in
Neonatal Medicine at Newcastle Neonatal Service Royal Victoria
Infirmary Newcastle upon Tyne NE1 4LP UK
Should you start feeds at a day of age
alice was born following spontaneous labour at 30 weeksrsquo
gestation she weighed 1300 g and is now 18 h old she was
briefly ventilated and then extubated to continuous positive
airway pressure 12 h ago in 35 oxygen she has had caffeine
citrate but still has intermittent episodes of self-correcting
apnoea she was commenced on iv 10 dextrose but this was
replaced by a parenteral amino acid solution (referred to as
lsquotPnrsquo) along with intralipid at 0900 this morning serum glucose
is 11 mmoll and blood pressure is 42 systolic
PaeDiatrics anD cHilD HealtH 184 20
arterial catheter in situ but there is no good evidence that this should delay the decision to start feeds Her glucose is high but this is quite common in a baby like this Could this be a sign of sepsis Caffeine does not affect the incidence of NEC2 The great-est risk factor for NEC in this case is prematurity
What else might be found on examination
Up until 24 h ago she was swallowing large amounts of amniotic fluid What will have changed since then
General examination should confirm peripheral perfusion lsquogestaltrsquo view (does she look lsquowellrsquo) and cardiovascular status lsquoBowel soundsrsquo are not usually helpful
The most important variable likely to affect gut perfusion is the arterial duct Precordial lsquoheaversquo and a loud murmur are sug-gestive but it is possible to have a significant ductal shunt in a baby with a normal examination Cardiac ultrasound will con-firm this diagnosis It might be better to treat a large shunt first with indometacin and to delay starting feeds for a further 24 h
It is not possible to assess gut perfusion clinically but normal perfusion elsewhere (adequate urine output usually indicates adequate renal perfusion) would be reassuring Most preterm babies have a few abdominal lsquoloopsrsquo visible but a distended abdomen with many palpable loops suggests ileus This might be secondary to sepsis or poor gut blood flow Preterm babies do not pass much meconium in the first 24ndash48 h
Balance of risks between starting and withholding feeds
Alice requires 35ndash4 gkgd of protein and 120 kcalkgd to grow3 This will initially be provided parenterally Delaying feeds increases the risk of gut villous atrophy and prolongs the need for lsquototal parenteral nutrition (TPN)rsquo TPN requires intravenous access and so increases the risk of sepsis and when prolonged use is required combined with the lack of enteral feeding may result in hepatic impairment
Delaying feeds may allow a gut that has been chronically under-perfused to re-establish more normal perfusion although normal gut endocrine function digestive enzyme upregulation and motility require a source of intraluminal nutrients1 A recent study suggested benefit from delaying the introduction of feeds4 but methodologi-cal problems exist5 Although a Cochrane meta-analysis suggested no benefit only two studies were included6 A large UK-based trial is examining the effect of early or late feeding in preterm infants who were born growth retarded following identification of antena-tal absent or reversed end diastolic flow in the umbilical artery7
When starting feeds what volume should be used
There are no good data to guide this decision We start with 24 mlkg (1 mlkgh) and then increase by this amount each day Most babies achieve full enteral feeds (ge150 mlkgd) by a week of age Feeding guidelines improve the outcome8 Measure-ment or assessment of gastric aspirates is not consistently useful in predicting subsequent feeding intolerance or development of NEC Aspirate volumes equivalent to or sometimes greater than the amount given in the preceding 1ndash2 h are usually normal Most aspirates have a greenish colour Thick bloody or intensely bile-stained aspirates require detailed assessment
0 copy 2008 elsevier ltd all rights reserved
Personal Practice
What else affects decisions and outcome
Feeding success is affected by sepsis and NEC Scrupulous atten-tion should be paid to hand washing and intravenous access and blood sampling should be minimized There is no good evidence to support the routine use of pro-kinetic agents or H2 blockers
The most important clinical intervention affecting the occur-rence of NEC is the use of breast milk9 All efforts should be directed at persuading parents of the benefits and supporting the process Some clinicians delay starting feeds for a further 24 h whilst expressed breast milk becomes available Donor breast milk might be equally efficacious10
RefeRenceS
1 Dorling J Kempley s leaf a Feeding growth restricted preterm
infants with abnormal antenatal Doppler results Arch Dis Child Fetal
Neonatal Ed 2005 90 F359ndash363
2 schmidt B roberts rs Davis P et al caffeine therapy for apnea of
prematurity N Engl J Med 2006 354 2112ndash2121
PaeDiatrics anD cHilD HealtH 184 20
3 embleton nD Pang n cooke rJ Postnatal malnutrition and growth
retardation an inevitable consequence of current recommendations
in preterm infants Pediatrics 2001 107 270ndash273
4 Berseth cl Bisquera Ja Paje VU Prolonging small feeding volumes
early in life decreases the incidence of necrotizing enterocolitis in
very low birth weight infants Pediatrics 2003 111 529ndash534
5 Menon G Boyle eM embleton nD et al introduction of enteral
feeds in preterm infants Pediatrics 2004 114 327ndash328
6 Kennedy Ka tyson Je chamnanvanikij s early versus delayed
initiation of progressive enteral feedings for parenterally fed low
birth weight or preterm infants Cochrane Database Syst Rev 2000
cD001970
7 wwwnpeuoxacukadept
8 Patole sK de Klerk n impact of standardised feeding regimens on
incidence of neonatal necrotising enterocolitis a systematic review
and meta-analysis of observational studies Arch Dis Child Fetal
Neonatal Ed 2005 90 F147ndash151
9 lucas a cole tJ Breast milk and neonatal necrotising enterocolitis
Lancet 1990 336 1519ndash1523
10 Boyd ca Quigley Ma Brocklehurst P Donor breast milk versus
infant formula for preterm infants systematic review and meta-
analysis Arch Dis Child Fetal Neonatal Ed 2007 92 F169ndash175
1 copy 2008 elsevier ltd all rights reserved
self-assessment
Case 1A term male infant born to consanguineous parents is assessed at 24 h of age due to poor feeding profuse yellow watery diar-rhoea and irritability He weighed 32 kg at birth and delivery was uneventful There was no polyhydramnios He has been breastfed since birth On examination he is pale with a non-tender but distended abdomen and reduced bowel sounds His weight is 275 kg and he looks dehydrated Examination is otherwise normal
Initial investigations (normal values in parentheses) showed
sodium 149 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 65 mmollitre (25ndash75)
creatinine 147 μmollitre (40ndash110)
chloride 119 mmollitre (95ndash105)
haemoglobin 172 gdl (140ndash200)
White blood cell count 80 times 109litre (100ndash260)
Platelet count 302 times 109litre (150ndash400)
arterial blood gas
ph 720 (730ndash745)
PcO2 23 kPa (46ndash60)
Bicarbonate 68 mmollitre (220ndash260)
Base excess minus186 mmollitre (minus20 to +20)
lactate 59 mmollitre (06ndash24)
An abdominal X-ray shows distended bowel loops with no intramural thickening or pneumoperitoneum (Figure 1)
He was given nil by mouth and received intravenous fluids and antibiotics His dehydration improved but the metabolic acidosis and diarrhoea persisted despite receiving no enteral feeds and the commencement of total parenteral nutrition Blood and stool cultures were negative
1 Which of the following best describes these results Choose ONE answer ONLY from the followingA Hypernatraemia hyperchloraemic metabolic acidosis
with increased anion gapB Hypernatraemia hyperchloraemic metabolic acidosis
with normal anion gap
Manish Sadarangani BM BCh MA MRCPCH is Clinical Research Fellow
at the Department of Paediatrics University of Oxford Centre for
Clinical Vaccinology and Tropical Medicine Churchill Hospital
Oxford OX3 7LJ UK
Shabna Rajapaksa MB BChir MA MRCPCH is Specialist Registrar in
Paediatrics at the Paediatric Intensive Care Unit John Radcliffe
Hospital Oxford OX3 9DU UK
Nicholas Mann MD FRCP FRCPCH DCH is Consultant Paediatrician at the
Department of Paediatrics Royal Berkshire Hospital Reading RG1
5AN UK
self-assessment
C Hypernatraemic dehydration and compensated metabolic acidosis
D Acute renal failureE Renal tubular acidosis
2 What is the likely diagnosis Choose ONE answer ONLY from the followingA Hirschsprung disease ndash long segmentB Cystic fibrosis with meconium ileusC Microvillus inclusion diseaseD Cowrsquos milk protein intoleranceE Lactose intolerance
3 What is the investigation of choice Choose ONE answer ONLY from the followingA Rectal biopsy with staining for acetylcholine receptorsB Immunoreactive trypsinC Gastrointestinal endoscopy and biopsyD Stool microscopy and cultureE Stool reducing substances
Case 2A 4-year-old boy presents with a 3 d history of jaundice and a florid rash He has had orange urine and there is no change in his stool colour His family originate from Kosovo and have lived in the UK for the last 8 years He has never left the UK There is no history of blood transfusion or sex-ual abuse The grandmother was recently diagnosed with hepatitis B
On examination he is well apyrexial and mildly jaundiced with cervical and axillary lymphadenopathy He has an exten-sive papular rash over the face extremities and trunk (Figure 2) There is 3 cm hepatomegaly with no splenomegaly or ascites Examination is otherwise normal
Figure 1 abdominal X-ray of baby
Paediatrics and child health 184 202 copy 2008 elsevier ltd all rights reserved
self-assessment
Initial investigations are as follows
haemoglobin 110 gdl (113ndash135)
White blood cell count 108 times 109litre (50ndash150)
Platelet count 278 times 109litre (150ndash400)
inr 10 (08ndash12)
aPt ratio 10 (08ndash13)
sodium 140 mmollitre (135ndash145)
Potassium 42 mmollitre (35ndash50)
Urea 56 mmollitre (25ndash75)
creatinine 65 μmollitre (45ndash120)
total bilirubin 66 μmollitre (0ndash15)
conjugated bilirubin 23 μmollitre (0ndash10)
alanine aminotransferase (alt) 2033 iUlitre (0ndash35)
alkaline phosphatase 987 iUlitre (71ndash234)
Gamma-glutamyl transferase (GGt) 870 iUlitre (0ndash51)
1 What is the name of this rash Choose ONE answer ONLY from the followingA Erythema multiformeB Erythema migransC GianottiminusCrosti syndromeD EczemaE Dermatitis herpetiformis
2 What is the most likely diagnosis Choose ONE Answer ONLY from the followingA Autoimmune hepatitisB Hepatitis BC Hepatitis DD Wilson diseaseE Alpha-1 antitrypsin deficiency
3 What is the best means of management Choose ONE answer ONLY from the followingA Isolation until the jaundice disappearsB ImmunosuppressionC Copper chelating agents and genetic counsellingD Patient and family education with consideration of
antiviral agentsE Liver transplantation
Case 3A 10-month-old boy presents with 3 weeks of vomiting and constipation ndash he is passing hard stools every 2ndash3 days He has fallen from the 9th to below the 04th centile in the last 6 weeks He passed meconium within the first 24 h of life On examina-tion he looks pale and there are some dysmorphic features ndash a short nose long philtrum and wide mouth He has normal heart sounds with a grade 3 ejection systolic murmur loudest at the upper right sternal edge Examination is otherwise normal
Initial investigations are as follows
haemoglobin 91 gdl (113ndash141)
total white blood cell count 124 times 109litre (60ndash170)
Platelet count 407 times 109litre (150ndash400)
sodium 144 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 78 mmollitre (25ndash75)
creatinine 78 μmollitre (45ndash120)
albumin 52 glitre (35ndash50)
corrected calcium 384 mmollitre (238ndash263)
Phosphate 167 mmollitre (099ndash157)
1 What is the most likely diagnosis Choose ONE answer ONLY from the followingA HyperparathyroidismB Acute leukaemiaC Williams syndromeD Hypervitaminosis DE Familial hypocalciuric hypercalcaemia
2 Which investigation would be most useful in establishing the diagnosis Choose ONE answer ONLY from the followingA Intact parathyroid hormone assayB Blood filmC Fluorescent in-situ hybridization for 7q1123 deletionD 25-hydroxyvitamin D assayE Urine calciumcreatinine ratio
3 Which of the following treatments would not be suitable for this patient Choose ONE answer ONLY from the followingA Low calcium dietB Normal saline infusionC FurosemideD CorticosteroidsE Bisphosphonates
Case 4A 10-week-old girl presents with a 2-day history of poor feed-ing Her mother has been concerned about weakness since birth She only has a flicker of movement in the arms none in the legs and has a weak cry She has been passing urine and opening her bowels normally She was born at full term by normal delivery and did not require any resuscitation at birth Normal fetal movements were felt antenatally and there was no polyhydramnios She is the first child of non- consanguineous parents and there is no significant family his-tory On examination she is alert and fixing and following appropriately She has a weak cry and a weak suck There is reduced central and peripheral tone with marked head lag
Figure 2 rash found on examination
Paediatrics and child health 184 203 copy 2008 elsevier ltd all rights reserved
self-assessment
Muscle power is grade 3 out of 5 in the arms and legs There is no muscle or tongue fasciculation and she has absent reflexes throughout The remainder of the examination is normal
Electromyogram shows irregular polyphasic motor unit potentials with marked instability consistent with a dener-vating and re-innervating process (Figure 3)
1 Which of the following additional investigations may be helpful Choose ONE answer ONLY from the followingA Nerve conduction studiesB Creatine kinase assayC Muscle biopsyD SMN1 gene analysisE All of the above
2 What is the most likely cause of this childrsquos symptoms Choose ONE answer ONLY from the followingA Congenital myotonic dystrophyB Duchenne muscular dystrophyC PraderminusWilli syndromeD Spinal muscular atrophyE Mitochondrial myopathy
3 What is the mode of inheritance of this disease Choose ONE answer ONLY from the followingA X-linked recessiveB Autosomal recessiveC Autosomal dominantD MitochondrialE Sporadic
Case 5A 13-year-old girl presents with a 3-week history of fever up to 40degC night sweats and headache She has a reduced appetite with some weight loss She has no other specific symptoms She was on holiday in China 7 months ago On examination she looks well and has a temperature of 387degC There is no lymphadenopathy and no rashes Examination is entirely normal
Results of investigations are as follows
haemoglobin 126 gdl (120ndash160)
total white blood cell count 132 times 109litre (43ndash108)
neutrophil count 115 times 109litre (25ndash75)
Platelet count 244 times 109litre (150ndash400)
Blood film neutrophilia with left shift
erythrocyte sedimentation rate 63 mmh (1ndash20)
c-reactive protein 219 mglitre (0ndash5)
Blood culture Streptococcus intermedius
from anaerobic bottle only
csf culture negative
Magnetic resonance imaging (MRI) of the brain shows acute frontal sinusitis with a large intracranial frontal extra-dural empyema (Figure 4)
1 Which of the following would be appropriate management Choose ONE answer ONLY from the followingA A 12-week course of intravenous antibioticsB Drainage of the frontal sinus followed by 2 weeks of
intravenous antibioticsC Drainage of the empyema followed by 2 weeks of
intravenous antibioticsD Drainage of the empyema and the frontal sinus
followed by 2 weeks of oral antibiotics
1151
1152
1153
1154
1155
1156
1157
1158
1159
1200
50ms 1mV
Figure 3 electromyogram recording from the patient Figure 4 Parasagittal section from mri scan of patient
Paediatrics and child health 184 204 copy 2008 elsevier ltd all rights reserved
self-assessment
E Drainage of the empyema and the frontal sinus followed by 8 weeks of intravenous antibiotics
2 Streptococcus intermedius is a potential pathogen in which of the following infections Choose ONE answer ONLY from the followingA Liver abscessB Urinary tract infectionC MeningitisD Thoracic empyemaE Pneumonia
3 Which of the following statements regarding lsquopyrexia of unknown originrsquo in children is false Choose ONE answer ONLY from the followingA Malignancy is the underlying pathology in 5ndash15 of
casesB An aetiology will be found in over 90 of casesC The most common cause is infectionD A rheumatological cause is found in 10ndash20 of casesE Familial Mediterranean fever can occur in children of
non-Mediterranean ethnicity
Answers
Case 11 AThe anion gap is a useful tool to differentiate the causes of a metabolic acidosis It is calculated by the equation
Anion gap = [Na K ] [Cl HCO ]3+ + minus minus+ minus +
It represents the effect of unmeasured anions on the plasma pH and is normally 10ndash18 mmollitre
2 CMicrovillus inclusion disease is a severe autosomal recessive enteropathy that is typically apparent within hours or days after birth It is the second most common cause of protracted diarrhoea in the newborn after infectious causes It is characterized by severe yellow watery diarrhoea and malabsorption due to hypoplasia andor atrophy of the villi of the small intestine secondary to an inherited defect in the brush border membrane This results in severe dehydration malnutrition and metabolic acidosis due to bicarbonate loss from the gut
3 CDiagnosis of microvillus inclusion disease is made on small bowel biopsy Electron microscopy findings are of intracellular brush border inclusions and densely packed apical cytoplasmic vesicular bodies indicating microvillous atrophy There is no cure Treatment is supportive with total parenteral nutrition and consideration of small bowel transplantation
Further reAding
Goulet O ruemmele f causes and management of intestinal failure
in children Gastroenterology 2006 130(suppl 1) s16ndash28
rhoads Jm Vogler rc lacey sr et al microvillus inclusion disease
In vitro jejunal electrolyte transport Gastroenterology 1991
100 811ndash817
Case 21 CGianottindashCrosti syndrome is a distinct self-limiting rash commonly associated with viral infections in children between 2 and 6 years of age It presents as multiple pink to redminusbrown papules or papulovesicles which may be pruritic and can become confluent Gianotti and Crosti initially described the exanthema as associated with hepatitis B virus and they termed it papular acrodermatitis of childhood It can occur in several viral diseases eg hepatitis A B and C coxsackie viruses and cytomegalovirus
2 BHepatitis is a syndrome characterized by inflammation or injury of liver cells which may develop into cell necrosis and subsequently fibrosis andor cirrhosis Biochemically there are raised liver enzymes The degree of transaminase elevation does not correlate with the severity of the disease process Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of viral hepatitis
3 DHepatitis B infection is transmitted via blood sexually or vertically Infection may be acute or chronic Diagnostic markers are the presence of surface antigen (HBsAg) and HBV DNA The presence of e antigen (HBeAg) indicates high infectivity Infected newborns have a 95 risk of becoming carriers this risk decreases with infection acquired later in childhood Approximately 15ndash25 of HBV carriers will die from cirrhosis or hepatocellular carcinoma Extrahepatic findings are more common in older children and include membranous glomerulonephritis and GianottiminusCrosti syndrome Fulminant hepatic failure occurs in severe cases resulting in persistent jaundice encephalopathy and coagulopathy Management includes counselling family members monitoring for ongoing liver disease and consideration of antiviral therapy
Further reAding
Brandt O abeck d Gianotti r Burgdorf W Gianotti crosti
syndrome J Am Acad Dermatol 2006 54 136ndash145
slowik mK Jhaveri r hepatitis B and c viruses in infants and
young children Semin Pediatr Infect Dis 2005 16 296ndash305
Case 31 CHypercalcaemia is uncommon in infancy The most common symptoms in this age group are irritability vomiting and constipation It may be a manifestation of Williams syndrome vitamin D or calcium excess as well as disorders associated with reduced bone formation such as hypophosphatasia or increased bone resorption such as malignancy Occasionally
Paediatrics and child health 184 205 copy 2008 elsevier ltd all rights reserved
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-
SympoSium neonatology
Resuscitation of the term and premature babyJonathan Wyllie
Abstractalthough most newly born babies establish normal respiration and
circulation without help up to 1minus2 may require some resuscitation
or stabilization Babies who do not establish adequate regular normal
breathing or who have a heart rate of less than 100 beatsmin or other
problems such as prematurity may require assistance the differences in
approach to the resuscitation of such babies originate in the physiology
and pathophysiology of acute asphyxia at birth However management
of airway and breathing remain the key features of resuscitation and
where cardiac depression has occurred this is nearly always due to hy-
poxia secondary to respiratory compromise therefore most babies will
respond within 2minus3 min of effective aeration of the lungs and the need
for intubation chest compressions or drugs is rare the international
liaison Committee on Resuscitation (ilCoR) evaluated evidence in 2000
and 2005 in order to provide guidelines for resuscitation they will do
so again for 2010 this evidence is limited in terms of both quantity and
quality and controversies still exist more research is needed to ensure
that our future actions are based upon evidence rather than history this
article will review the recommended approach to resuscitation as well as
some newer evidence
Keywords guidelines neonatal newborn premature resuscitation
Background
In the UK 669 601 babies were born alive in 2006 and most made the transition to extrauterine life without problems Those babies who did not establish adequate regular normal breathing or who had a heart rate of less than 100 beatsmin may have required assistance1 Factual evidence concerning the true requirement for resuscitation at birth is sparse Up to 10 of newborns may require some assistance to begin breathing with less than 1 needing extensive resuscitation2 However just because a baby received resuscitation does not necessarily mean that it was required and rates of intervention may be altered by educa-tion34 or the personnel present at deliveries5 In a UK tertiary centre with a standard approach to resuscitation at birth up to 12 of all babies received some airway assistance with just over 1 being intubated3 In Sweden only 1 of babies over 2500 g required mask or endotracheal tube ventilation at birth of which most responded to the former4
Jonathan Wyllie MBChB FRCPCH is Consultant Neonatologist at the James
Cook University Hospital Marton Road Middlesbrough TS4 3BW UK
paeDiatRiCS anD CHilD HealtH 184 16
Sometimes it is possible to predict babies who are likely to have respiratory depression at birth and to have appropriate per-sonnel present at delivery Guidelines for attendance at deliveries will vary with institution but even when almost 40 of deliv-eries are attended there may still be a further 15 of babies who require unexpected resuscitation5 a proportion that seems to remain whatever changes are made
The physiology of babies requiring help at birth has been summarized previously167 It allows a logical approach to resus-citation (Figure 1) when evidence is lacking and may prompt further research
Resuscitation at birth
PreparationAt birth resuscitation is more likely in babies with intrapartum evidence of significant fetal compromise those less than 35 weeksrsquo gestation those delivering vaginally by the breech and in multiple births Personnel trained in newborn resuscitation should be available at every delivery1 Someone experienced in tracheal intubation and advanced resuscitation should also be easily available for normal low-risk deliveries in hospital and ideally in attendance for deliveries with an increased likelihood of needing resuscitation In the latter cases the equipment and environment can be prepared beforehand including a discussion with the parents Wash your hands put on gloves and consider what help may be needed
Cord clampingAt birth it has long been known that delay in clamping the cord will lead to less anaemia in babies and reduce subsequent iron deficiency8 However few hospitals have practised this interven-tion due to worries about hypothermia and the need to resusci-tate or stabilize babies In developed countries the advantages seemed to be outweighed by the potential disadvantages A recent randomized controlled study of delayed clamping of the cord in premature babies found that the intervention group had less late-onset sepsis and fewer intraventricular haemorrhages9 This is a low-risk strategy which needs further evaluation in order to introduce it without increasing other risk factors in pre-mature deliveries
Assessment and temperature controlAssessment and temperature control for the newborn baby should occur at all deliveries The assessment indicates the need for resuscitation Babies may vary from 23 to 40+ weeksrsquo ges-tation and in weight from 500 to 5000 g They are born naked and wet and if left cannot cope with an environmental tem-perature of less than 32degC However if the term baby is imme-diately dried put skin-to-skin with the mother and covered the delivery room temperature can be as low as 25ndash28degC Obviously the smaller the baby the greater the surface area to mass ratio and the greater the risk of hypothermia Compromised babies are particularly vulnerable10 and hypothermia will lower oxygen tension11 increase metabolic acidosis12 and inhibit surfactant production13
An effective method of maintaining the temperature of prema-ture babies less than 28 weeksrsquo gestation is wrapping them with plastic before drying and then placing them under a radiant
6 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Dry the babyRemove any wet towels and cover
Start the clock or note the time
Give 5 inflation breathsLook for a response
If no increase in heart rate look for chest movement
Re-check head positionApply Jaw thrust
Repeat inflation breathsLook for a response
If no increase in heart rate look for chest movement
Try alternative airway opening manoeuvresRepeat inflation breaths
Look for a response
If no increase in heart rate look for chest movement
If the heart rate is not detectable or slow (lt60)Start compressions
3 compressions to each breath
Reassess heart rate every 30 secondsConsider venous access and drugs
Assess colour tone breathing and heart rate
Open the airway
If not breathing
If still not breathing
If no response
If still no response
When the chest is moving
If meconium present
Baby breathing wellDo not suction the airway
Baby floppy and not breathing wellConsider inspection and suction before
inflation breaths
Head in neutral position
Inflation breathsUse a well-fitting face mask
connedted to a
pressure-limited gas supply
Each breath 2ndash3 seconds
duration at 30 cm H2O for a
term baby
Get help from a second personto support the airway andor
inspect the oropharynx under
direct vision and consider
suction andor insert an
oropharyngeal airway
Chest compressionsCompvent ratio 31
Rate 120 events per minute
Ensure the chest moves with each ventilation breath
If breathingReassess heart rate and monitor baby
If heart rate is satisfactory but increasingContinue ventilation breaths at about 30 per
minute until baby is breathing adequately
If heart rate is satisfactory but increasingContinue ventilation breaths at about 30 per
minute until baby is breathing adequately
If heart rate is increasingStop compressions
Continue ventilation breaths at about 30 per
minute until baby is breathing adequately
If the chest is not movingRecheck head position and repeat inflation
breaths If competent consider intubation
If the chest is still not movingThe airway is the problem
Figure 1 newborn life support (Courtesy of the Resuscitation Council uK)
heater14 There is a small risk of hyperthermia so the temperature must be monitored carefully
An assessment is made of the babyrsquos colour tone respira-tions and heart rate127 The most important of these is heart rate and a stethoscope is more reliable than cord pulsation15 How-ever saturation monitors may offer a more reliable assessment of both heart rate and colour16 but their interpretation requires a detailed knowledge of normal saturations at birth at differing gestations A baby who is apnoeic and floppy in the absence of neurological disease is unconscious and likely to be in terminal apnoea however this does not change the initial approach other
paeDiatRiCS anD CHilD HealtH 184 167
than the need to summon help early APGAR scores are never calculated to guide resuscitation
Airway
If a baby is in primary apnoea then with an open airway the first gasp will start to aerate the lungs and most babies will be able to lsquoresuscitatersquo themselves as shown in physiological stud-ies on animals Neutral positioning of the babyrsquos head chin lift jaw thrust oropharyngeal airways and endotracheal intubation may all be helpful in certain situations if performed correctly17
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Endotracheal intubationThe placement of an endotracheal tube has long been the gold standard of airway control and this remains true in the unconscious baby if it is correctly sized placed and fixed in a timely manner However experience is directly related to effec-tiveness in endotracheal intubation1819 and the success rate of less experienced clinicians such as a resident (STA1-3) or a fel-low (STA3-5) is lower varying between 33 and 68 Even senior neonatologists often take longer than guidelines recom-mend19 Experienced clinicians may judge correct endotracheal position visually or by an increase in heart rate with the first breaths but detection of exhaled carbon dioxide will give more rapid confirmation in larger babies12171920 and this can be par-ticularly useful for less experienced clinicians or those supervis-ing them However not all systems for the detection of exhaled carbon dioxide work in the smallest premature infants
Laryngeal masksLaryngeal masks may be effective for ventilating term newborn babies but there are few data for small premature infants There have been reports of dislodged laryngeal airways during paedi-atric arrests when chest compressions have been administered Although success of placement at first attempt by paediatri-cians is greater with a laryngeal mask than with an endotra-cheal tube21 the only and small randomized controlled trial in the delivery room favoured endotracheal intubation when per-formed by an anaesthetist22 Based mainly upon case reports the laryngeal mask can be recommended when positioning and mask ventilation and endotracheal intubation have failed to secure the airway but not as yet as a primary method of airway control
MeconiumIn 2000 Wisewell et al23 reported a large randomized controlled trial showing that tracheal intubation and suctioning of meco-nium-stained but vigorous babies at birth did not reduce the incidence or severity of meconium aspiration syndrome More recently another randomized trial has now shown that suction-ing on the perineum similarly offers no benefit24 Neither of these practices is recommended but intubation and suction of meconium from the trachea of non-vigorous babies born through meconium-stained liquor is still recommended
Breathing
In the apnoeic baby the first breaths establish the resting lung volume and aerate the fluid-filled alveoli This mechanical effect aided by surface tension within the alveoli causes the initial fall in pulmonary vascular resistance Experimentally this effect occurs even if the lungs are ventilated with nitrogen but is increased when air is used presumably due to the vasodilator effect of 21 oxygen The mechanical stretching of the lung also triggers the activation of cyclo-oxygenase beginning the production of prostacyclin Bradykinin is produced which has a further direct vasodilator effect and also possibly via prostacyclin Therefore adequate airway control and passive ventilation is vital not only because babies requiring resuscitation at birth have an almost uniformly respiratory aetiology but also in order to promote post-natal adaptation and reverse any maladaptation
paeDiatRiCS anD CHilD HealtH 184 16
In term babies peak ventilatory pressures of 20ndash30 cmH2O may be required but the minimal pressure needed to achieve an improvement in heart rate should be used or if there is no response chest wall movement Longer breaths at lower pressure may be more effective in displacing alveolar fluid and establish-ing the resting lung volume in lungs with sufficient surfactant and may improve initial oxygenation However premature new-borns are obviously physiologically and anatomically less pre-pared for delivery than infants at term Over-inflation has been implicated in histological lung damage in animal models and high tidal volumes appear to be equally damaging whether given before or immediately after administration of surfactant How-ever the same effect is not seen if these excessive tidal volumes are delivered 15 min after administration of surfactant2526 It is now thought that both excess end expiratory volume and inad-equate end-expiratory volume may cause lung damage2728 In premature infants it would therefore seem sensible to use lower pressures of 20ndash25 cmH2O12 delivered in a controlled way to prevent over-inflation and to apply positive end-expiratory pres-sure (PEEP) to prevent damage from under-inflation PEEP also improves both lung compliance and gas exchange2930 Without PEEP the airways collapse during the expiratory phase in animal models of newborn resuscitation
If animal data can be extrapolated it would also seem appro-priate to give surfactant as soon as possible to premature babies in order to ameliorate damage2526
The majority of newborn infants requiring resuscitation will re-establish regular respiration after administration of a few breaths which may be due to Headrsquos paradoxical reflex by which the inflation triggers an inspiratory effort
VentilationOnce the lungs are aerated if the newborn remains apnoeic ventilation should be continued at 30ndash60 breathsmin avoiding hyperventilation and using the minimum pressure possible to maintain a heart rate greater than 100 beatsmin
Face mask the majority of infants who require ventilation receive it via a face mask This may be attached to a bagvalve system with a spring lsquoblow offrsquo system or a lsquoT-piecersquo with a set flow and pressure It is important to realize that the bagvalve system is flow sensitive and that the harder the operator presses the greater the flow and the higher the delivered pressure In fact 60 cmH2O can be achieved with vigorous squeezing of a self-inflating bag Therefore it may be advantageous that most opera-tors are unlikely to be as effective as they suppose in creating a seal with the mask31 This is a skill that requires tuition and prac-tice31 In delivering a set pressure T-piece systems such as the Tom Thumbcopy or Neopuffcopy perform better than any bagminusvalve system but require a gas supply There is no evidence that lung compliance can be assessed using any bag system
Continuous airway pressure case series have suggested that early or delivery room use of continuous positive airway pres-sure (CPAP) in premature babies may reduce chronic lung dis-ease There have been two randomized trials of which one was a pilot study The data from the COIN trial do not show any advan-tage other than a reduction in intubation and surfactant use in the intervention group However an excess of pneumothorax
8 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
was also reported The Vermont Oxford Network and the SUP-PORT trials will provide further data but at present the delivery room use of CPAP cannot be widely recommended and should be limited to those units experienced in its use or taking part in research
Air or oxygen oxygen has been in widespread use for resuscita-tion at birth since the 1930s and even hyperbaric oxygen was seriously supported in the 1960s For many years there have been concerns about tissue damage from oxygen deprivation during and after resuscitation It became evident in the 1950s that unrestricted oxygen therapy could have serious conse-quences for future vision More recently concerns have been raised about potential adverse effects on respiratory physiology cerebral circulation and tissue damage from oxygen free radicals even during resuscitation A meta-analysis of four human studies demonstrated a reduction in mortality and no evidence of harm in infants resuscitated in air versus 100 oxygen3233 However there are several significant methodological concerns with these studies and the results should be interpreted with caution There is insufficient evidence to recommend any specific concentration of oxygen to be used for newborn resuscitation Monitoring the oxygen saturation of babies may be helpful but as yet there are no time-related normal target ranges and healthy term babies may take up to 10 min to achieve preductal oxygen saturation of greater than 95 and up to 60 min to achieve this postductally
There is therefore equipoise which would be open to an appropriate randomized controlled trial In the meantime the evidence only supports use of either 21 or 100 oxygen It is provoking to realize that if air had been in constant use since the 1930s there would be insufficient evidence for use of supple-mental oxygen
Circulation
Early resuscitation (temperature control airway breathing) provides oxygenated blood in the pulmonary arterioles which if returned to the heart causes the rate to increase34 If due to acidosis and hypoxia the circulation is ineffective then chest compressions may be needed They should be commenced when the heart rate remains below 60min despite effective airway and breathing management127 The best technique is using two hands to encircle the chest1 A ratio of three compressions to one breath is internationally accepted127 but has no evidence to support it Research has shown that neither compressions nor drugs will work in this situation without oxygenated blood so effective lung aeration and ventilation is essential A logical approach would be to fill the alveoli with air and to compress the chest until they are empty However training and teamwork require an agreed ratio which has therefore not changed since guidelines were first agreed internationally Success is assessed by an increase in heart rate which should therefore be assessed every 30 s Compressions stop when the spontaneous heart rate is greater than 60 beatsmin
In hypoxic newborn animal models successful resuscitation can restore cardiac output and blood pressure to levels above baseline within 5ndash10 min However it should be noted that there is a decline to 30 lower than basal levels within 2 h and that blood pressure is relatively spared suggesting an even greater
paeDiatRiCS anD CHilD HealtH 184 16
reduction in tissue perfusion This should be considered in the later care of any neonate who was hypoxic at birth
Drugs
Neonatal bradycardia at birth is almost always due to hypoxia plusmn acidosis and therefore drugs are rarely needed Adrenaline (epi-nephrine) is reported as being used in between 1 and 4 babies per 2000 births which is a large variation in practice Reported success is also variable and must be interpreted in light of this variation The use of drugs in extremely premature infants is con-troversial Some data suggested good outcomes for babies below 28 weeksrsquo gestation given adrenaline but these were flawed by high numbers of babies receiving resuscitative drugs some before the airway had been appropriately managed Audit data now suggest a poor outcome such that many clinicians would now council against the use of adrenaline and other drugs to resuscitate extremely premature newborn babies
Adrenaline (epinephrine)In 2003 a Cochrane review of randomized controlled trials involv-ing adrenaline use for resuscitation of neonates was unable to identify a single clinical trial35 Despite the lack of human neo-natal data animal models show the potential of adrenaline in asphyxial cardiac arrest and it is reasonable to use it when ade-quate ventilation and chest compressions have failed to increase the heart rate above 60 beatsmin Use 10ndash30 μgkg intrave-nously and preferably via an umbilical venous line The tracheal route cannot be recommended but if used it is likely that doses within this range will be ineffective and 100 μgkg might be tried However the safety of such doses has not been studied
BicarbonateThe use of bicarbonate has long been controversial but many of the concerns relate to the rapid correction of acidosis in neonates after resuscitation or the routine use of bicarbonate infusion nei-ther of which can be advocated There are no published human neonatal data to support its use although some exist from animal studies Animal data have also shown that the binding of adren-aline to receptors in the myocardium is significantly impaired by lactic acidosis and recent work on human lymphocyte beta-adrenergic receptors supports this view Whether this is also true of the more important alpha receptors is unknown In practice reversing intracardiac acidosis may improve myocardial function and assist in achieving a return of spontaneous circulation 1ndash2 mmolkg of bicarbonate may be given but this remains a contro-versial area
VolumeVolume expansion should only be given when it is suspected that the baby has suffered blood loss or the infant appears to be in shock (pale poor perfusion weak pulse) and has not responded adequately to other resuscitative measures If there is no history suggestive of blood loss shock is most likely to be due to myo-cardial dysfunction in which case fluids should be administered cautiously The most logical replacement fluid would be blood but in its absence isotonic crystalloid rather than albumin is the solution of choice given in 10 mlkg aliquots and observing the response Three randomized trials in neonates have shown
9 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
isotonic crystalloid to be as effective as albumin for the treat-ment of hypotension but none has examined either the relative or actual effectiveness in resuscitation A recent blinded randomized study comparing normal saline albumin or no volume expansion in a normovolaemic asphyxiated neonatal animal model showed that volume expansion was not beneficial and made a number of parameters worse36
NaloxoneNaloxone is not recommended as part of the initial resuscita-tion of newborns with respiratory depression Before it is given supporting ventilation should have restored the heart rate and colour The dose is 100 μgkg intravenously or intramuscularly Tracheal administration cannot be recommended Although administration of naloxone to neonates who have been exposed to maternal opioids during labour is a practice of long-standing it lacks the proper evidence of efficacy
Non-response to resuscitation
There are few more frightening situations professionally than applying the correct interventions in resuscitating or stabilizing a baby and getting no response Each stage must be adequately performed before moving onto the next and this requires regular reassessment When experienced help is needed at a newborn resuscitation it is usually the airway and ventilation that require correction If the heart rate does not increase this usually means that the lungs have not been successfully aerated In some cases however it may mean that the heart cannot respond as the cir-culation is inadequate In this situation the only way to check that the lungs have been successfully aerated is to see the chest move with ventilation or to obtain evidence of ventilation from a detector of exhaled carbon dioxide If you do not see chest movement after another five breaths the most likely cause is an obstructed airway either due to incorrect positioning or because the jaw has not been drawn forwards An oropharyngeal airway can be very helpful at this point especially in the term baby Only very occasionally is the airway blocked by mucus vernix blood or meconium but if the airway is guaranteed and there is no heart rate response or chest movement this should be sought by direct suction of the trachea even in the absence of any meconium staining of liquor Pneumothoraces can occur spontaneously after delivery but are rare at resuscitation carried out with pressure-limited devices Equally rare are diaphragmatic hernias that have not been diagnosed antenatally giving problems at resuscitation
If the chest is moving but the heart rate has not responded to resuscitation consider rare possibilities such as fetal blood loss pneumothorax or heart block (mothers with undiagnosed systemic lupus erythematosis delivered for fetal bradycardia) as possibilities With adequate ventilation there is no evidence of oxygen concentrations less than 100 being responsible for prolonged bradycardia or failure to respond although current practice would support increasing the delivered oxygen concen-tration if resuscitation had been commenced using air
Outcome
The prognosis for the full-term baby subjected to sudden acute asphyxia is usually good provided the episode does not last for
paeDiatRiCS anD CHilD HealtH 184 17
long Most babies resuscitated from primary apnoea have no sequelae secondary to the resuscitation Many babies who start to breathe again regularly within 20 min of the circulation being restored recover completely but it is rare for a baby who is still gasping after 30 min to recover
The prognosis for the preterm baby of less than about 34 weeksrsquo gestation subjected to severe acute anoxia is less predict-able This is because of the risk of secondary intraventricular haemorrhage or periventricular intracerebral haemorrhage andor infarction after even a relatively brief asphyxial episode espe-cially in the period immediately around birth
The effects of chronic hypoxia are also difficult to predict but a reasonably clear idea of the extent of the problem should be obtainable within 36ndash48 h of the original chronic asphyxial insult A mild short-lasting state of hyperexcitability usually car-ries a good prognosis even if there is seizure activity but more severe symptoms can be associated with permanent handicap This is seen especially in infants with encephalopathy requiring ventilation
REFERENCEs
1 Biarent D Bingham R Richmond S et al european Resuscitation
Council guidelines for Resuscitation 2005 Section 6 paediatric life
support Resuscitation 2005 67(suppl 1) S97ndashS133
2 international liaison Committee on Resuscitation part 7 neonatal
resuscitation Resuscitation 2005 67 293ndash303
3 Singh J Santosh S Wyllie J mellon a effects of a course in
neonatal resuscitation - evaluation of an educational intervention
on the standard of neonatal resuscitation Resuscitation 2006 68
385ndash389
4 palme-Kilander C methods of resuscitation in low-apgar-score
newborn infants - a national survey Acta Paediatr 1992 81
739ndash744
5 Kroll l twohey l Daubeney p et al Risk factors at delivery and
the need for skilled resuscitation Eur J Obstet Gynecol Reprod Biol
1994 44 175ndash177
6 Wyllie Jp Resuscitation of the newborn The Foundation Years
2007 3(4) 153ndash157
7 Richmond S ed newborn life Support Resuscitation at Birth
london Resuscitation Council 2006
8 Ceriani Cernadas Jm Carroli g pelligrine l et al the effect of timing
of cord clamping on neonatal venous hematocrit values and clinical
outcome at term a randomized controlled trial Pediatrics 2006
117 e779ndashe786
9 mercer JS Vohr BR mcgrath mm padbury JF Wallach m oh W
Delayed cord clamping in very preterm infants reduces the incidence
of intraventricular hemorrhage and late-onset sepsis a randomized
controlled trial Pediatrics 2006 117 1235ndash1242
10 Dahm lS James lS newborn temperature and calculated heat loss
in the delivery room Pediatrics 1972 49 504ndash513
11 Stephenson J Du J tk o the effect of cooling on blood gas
tensions in newborn infants J Pediatr 1970 76 848ndash852
12 gandy gm adamsons Jr K Cunningham n Silverman Wa James lS
thermal environment and acid-base homeostasis in human infants
during the first few hours of life J Clin Invest 1964 43 751ndash758
13 gluck l Kulovich mV eidelman ai et al Biochemical development
of surface activity in mammalian lung pulmonary lecithin synthesis
0 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
in the human fetus and newborn and etiology of the respiratory
distress syndrome Pediatr Res 1972 6 81ndash99
14 Vohra S Roberts RS Zhang B Janes m Schmidt B Heat loss
prevention (Help) in the delivery room a randomised controlled
trial of polyethylene occlusive skin wrapping in very preterm infants
J Pediatr 2004 145 750ndash753
15 owen CJ Wyllie Jp Determination of heart rate in babies at birth
Resuscitation 2004 60 213ndash217
16 orsquoDonnell Cp Kamlin Co Davis pg Carlin JB morley CJ Clinical
assessment of infant colour at delivery Arch Dis Child Fetal
Neonatal Ed 2007 92 F465ndashF467
17 international liaison Committee on Resuscitation part 13 neonatal
Resuscitation guidelines Circulation 2005 112(suppl 24)
iV188ndashiV195
18 leone ta Rich W Finer nn neonatal intubation Success of
pediatric trainees J Pediatr 2005 146 638ndash641
19 orsquoDonnell Cp Kamlin Co Davis pg morley CJ endotracheal
intubation attempts during neonatal resuscitation success
rates duration and adverse effects Pediatrics 2006 117
e16ndash21
20 Repetto Je Donohue pa-CpK Baker SF Kelly l nogee lm use of
capnography in the delivery room for assessment of endotracheal
tube placement J Perinatol 2001 21 284ndash287
21 gandini D Brimacombe JR neonatal resuscitation with laryngeal
mask airway in normal and low birth weight infants Anesth Analg
1999 89 642ndash643
22 esmail n Saleh m ali a laryngeal mask airway versus endotracheal
intubation for apgar score improvement in neonatal resuscitation
Egypt J Anesthiol 2002 18 115ndash121
23 Wiswell te gannon Cm Jacob J et al Delivery room management
of the apparently vigorous meconium-stained neonate results of
the multicenter international collaborative trial Pediatrics 2000
105 1ndash7
24 Vain ne Szyld eg prudent lm Wisewell te aguilar am Vivas ni
oropharyngeal and nasopharyngeal suctioning of meconium-stained
neonates before delivery of their shoulders multicentre randomised
controlled trial Lancet 2004 364 597ndash602
25 Bjorklund lJ ingimarsson J Curstedt t larsson a Robertson B
Werner o lung recruitment at birth does not improve lung function
in immature lambs receiving surfactant Acta Anaes Scand 2001 45
986ndash993
26 Bjorklund lJ ingimarsson J Curstedt t et al manual ventilation
with a few large breaths at birth compromises the therapeutic effect
of subsequent surfactant replacement in immature lambs Pediatr
Res 1997 42 348ndash355
paeDiatRiCS anD CHilD HealtH 184 17
27 taskar V John J evander e Robertson B Jonson B Surfactant
dysfunction makes lungs vulnerable to repetitive collapse and re-
expansion Am J Respir Crit Care Med 1997 155 313ndash320
28 muscedere Jg mullen JB gan K Slutsky aS tidal ventilation at low
airway pressures can augment lung injury Am J Respir Crit Care Med
1994 149 1327ndash1334
29 nilsson R grossman g Robertson B Bronchiolar epithelial lesions
induced in the premature rabbit neonate by short periods of artificial
ventilation Acta Pathol Microbiol Scand 1980 88 359ndash367
30 probyn me Hooper SB Dargaville pa et al positive end expiratory
pressure during resuscitation of premature lambs rapidly improves
blood gases without adversely affecting arterial pressure Pediatr
Res 2004 56 198ndash204
31 Wood Fe morley CJ Dawson Ja et al improved techniques
reduce face mask leak during simulated neonatal resuscitation
study 2 Arch Dis Child Fetal Neonatal Ed in press doi101136
adc2007117788
32 tan a Schulz a orsquoDonnell CpF Davis pg air versus oxygen for
resuscitation of infants at birth Cochrane Database Syst Rev 2004
(3) CD002273
33 Davis pg tan a orsquoDonnell Cp Schulze a Resuscitation of newborn
infants with 100 oxygen or air a systematic review and meta-
analysis Lancet 2004 364 1329ndash1333
34 Dawes g Fetal and neonatal physiology Chicago year Book
publisher 1968 p 141ndash159
35 Ziino aJa Davies mW Davis pg epinephrine for the resuscitation
of apparently stillborn or extremely bradycardic newborn infants
Cochrane Database Syst Rev 2003 (2) CD003849
36 Wyckoff m garcia D margraf l perlman J laptook a Randomized
trial of volume infusion during resuscitation of asphyxiated neonatal
piglets Pediatr Res 2007 61 415ndash420
Practice points
bull Resuscitation at birth is different from that at all other times
of life
bull a standard approach can be applied to most newborn
resuscitation
bull guidelines are based on a rigorous evaluation of evidence
where possible
bull evidence is sparse but evolving
bull most preterm babies require stabilization rather than
resuscitation
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Acidndashbase physiology and blood gas interpretation in the neonateSusern tan
morag Campbell
Abstractacidndashbase balance describes the complex processes that work to main-
tain a stable extracellular pH for optimal cellular function the process
of balancing the production and neutralization of tissue acid provides a
great challenge for newborn infants who have significantly higher rates
of acid production than adults Factors which help maintain a stable
acidndashbase balance include buffers the respiratory system and renal sys-
tem Both intracellular and extracellular buffers resist changes in pH
the most important extracellular buffer system for maintaining stable
pH is the bicarbonate system in response to acidosis or alkalosis the
respiratory system balances the production of acid with the clearance
of Co2 by altering respiratory rate the kidneys provide a delayed but
sustained response to pH imbalance by excreting either acidic or alkaline
urine in response to systemic acidosis and alkalosis respectively in sick
premature infants these systems have a limited capacity completely to
control pH this review discusses the physiology of the three systems
which control acidndashbase balance patterns of clinical abnormalities in
acidndashbase status and their underlying causes are discussed We present
a systematic approach to blood gas analysis and interpretation in new-
born infants
Keywords acidosis alkalosis bicarbonate bloodndashgas analysis
metabolic pH
Introduction
Blood gas analysis is a routine procedure performed on newborn babies receiving respiratory support in the neonatal intensive care The combination of invasive and non-invasive assessment of ventilation and oxygenation enables clinicians appropriately to modify respiratory care according to each individual babyrsquos rapidly changing clinical status
Understanding the fundamentals of acidndashbase balance helps us to use blood gas analysis not only to assess respiratory sta-tus but also to provide information on metabolic status and the adequacy of tissue perfusion
Susern Tan MBBS MRCP is Clinical Fellow at the Neonatal Intensive Care
Unit 6th Floor North Wing St Thomasrsquo Hospital London SE1 7EH UK
Morag Campbell MBChB MRCP is Consultant Neonatologist at the
Neonatal Intensive Care Unit 6th Floor North Wing St Thomasrsquo
Hospital London SE1 7EH UK
paeDiatRiCS anD CHilD HealtH 184 17
What is understood by acid-base balance
Acidndashbase balance refers to the complex physiological processes used by the body to maintain a stable extracellular pH1 A serum pH within the range of 735ndash745 provides the ideal environment for cellular metabolism Maintaining a stable pH is critical as the metabolic activity of proteins is pH dependent and small changes in hydrogen ion (H+) concentration can potentially alter physio-logical function
Acids are substances that yield free H+ in solution while a base accepts H+ and in solution combines with an acid to neu-tralize it In the normal metabolic state H+ are continuously pro-duced and neutralized to maintain a steady pH balance12 The rate of H+ production is two to three times higher in neonates because of their rapid growth rates and increased acid production from protein turnover and bone mineralization The challenge of maintaining a stable pH through processing and neutralizing H+ is therefore greatest in newborn infants
Using exact values of H+ concentration to assess acidndashbase status is cumbersome and it is more commonly expressed as pH defined by the equation
pH = minuslog H+
Maintaining acidndashbase balance
The balance between production and excretion of acids in the body is controlled by buffer systems which have an immediate effect and by the respiratory and the renal systems
Buffer systemsBuffer solutions resist change in pH when acid or alkali is added due to their capacity to absorb or give up H+ The three main buffer systems in the body are the bicarbonate phosphate and protein systems1ndash3 The protein and phosphate buffer systems are intracellular and act as lsquosinksrsquo for extracellular H+ which are exchanged with intracellular potassium (K+) and sodium ions (Na+) In an acute metabolic acidosis hyperkalaemia may develop due to this H+ exchange4
The bicarbonate buffer system is extracellular and consists of a mixture of carbonic acid (H2CO3) and sodium bicarbon-ate (NaHCO3) This buffer system helps maintain a stable pH by soaking up excess H+ with HCO3
minus which in solution forms carbonic acid (H2CO3) Carbonic acid is a weak acid and readily dissociates to give CO2 which is transported in dissolved form to the lungs for excretion
H+ + HCO3minus harr H2CO3 harr H2O + CO2
The bicarbonate system therefore completes the neutraliza-tion of excess H+ and a stable plasma pH is maintained The relationships between pH HCO3
minus and CO2 in this system are described by the HendersonndashHasselbalch equation15
pH = 61 + log HCO3minus003 times CO2
where 61 is the log of the dissociation coefficient of carbonic acid and 003 the solubility of CO2 in plasma Buffers are most potent when there are equal amounts of H+ and HCO3
minus in solution The
2 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
bicarbonate system is not a potent buffer however as HCO3minus
and CO2 are readily altered by the body this system plays a very powerful role in pH homeostasis15
Respiratory regulationThe respiratory system adapts within minutes to hours as part of the acute response to acidosis This system modifies pH by balancing production of H+ with ventilatory clearance of CO2
H+ directly stimulates chemoreceptors in the respiratory cen-tre of the brainstem producing an increase in respiratory rate26 The response to respiratory acidosis is very rapid as CO2 easily diffuses across the bloodndashbrain barrier however in metabolic acidosis compensation is delayed until plasma bicarbonate fully equilibrates with cerebrospinal fluid (CSF) bicarbonate There is an inverse relationship between alveolar ventilation and partial pressure of dissolved carbon dioxide (PaCO2) a reduction in alveolar ventilation raises PaCO2 and decreases pH Changes in pH therefore affect alveolar ventilation and conversely changes in alveolar ventilation cause significant changes in pH
Renal regulationThe kidneys provide a delayed but sustained response to acidndashbase imbalances by excreting either acidic or alkaline urine In full-term and preterm babies the capacity for acid excretion and bicarbonate reabsorption is reduced as glomerular filtration rates are low and tubular function immature7 Renal function matures with gestation postnatal age and glucocorticoid and thyroid hormones78 Due to their limited capacity to preserve HCO3
minus newborn infants have lower serum bicarbonate levels and are predisposed to acidosis7
Bicarbonate is not effectively reabsorbed due to its size and electrical charge Instead intraluminal HCO3
minus combines with secreted H+ in tubular luminal fluid to produce carbonic acid which dissociates to give H2O and CO2 This CO2 diffuses into tubular cells combines with intracellular H2O and forms carbonic acid which liberates HCO3
minus and H+ HCO3minus is then
recovered to the circulation by exchange for chloride ions (Clminus) through the basal cell membrane247
Renal acid secretion occurs at all sites except the loop of Henle Primary active transport accounts for 5 and secondary for the remaining 95 of total H+ excretion Secondary trans-port involves an exchange between luminal Na+ and intracel-lular H+ Both ions bind to a membrane transport protein The Na+ concentration gradient between the tubular lumen and cells enables Na+ drag into the cell which generates energy to fuel active H+ excretion into the tubular lumen1ndash47
Quantifying acidosis
Standard base excess is a calculated value derived from PaCO2 and pH It is expressed as the mmollitre of base above or below normal buffer bases required to correct the pH to 74 at a PaCO2 of 40 mmHg A negative base excess or base deficit indicates an acidosis while a positive base excess indicates a relative alkalosis15
Anion gap is the measured difference between anions and cations in the blood
Anion gap = (Na+ + k+) minus (HCO3+Clminus)
paeDiatRiCS anD CHilD HealtH 184 17
Calculation of the anion gap enables clinicians better to define the underlying cause of a metabolic acidosis9 The common causes of an increased anion gap acidosis in neonates include lactic acidosis due to tissue hypoperfusion and hypoxia it may also be seen with certain inborn errors of metabolism and in uraemia910 The anion gap can help distinguish between the rela-tively benign non-anion gap hyperchloraemic acidosis seen in premature infants and a pathological lactic acidosis due to poor end-organ perfusion1011
Strong ion theory
Stewart described a complex acidndashbase model which proposed that H+ concentration results from the dissociation of water which is influenced by PaCO2 the strong ion difference and plasma weak acids12
Strong ions are ions that dissociate at normal body pH and include Na+ K+ and Clminus Weak acids in plasma which contrib-ute include albumin inorganic phosphate and plasma proteins their concentrations do not change with pH and are therefore a constant The effect of these factors and other unmeasured tissue ions on acidndashbase status can be quantified by the calculation of the strong ion gap (SIG)112 In the neonatal unit it is perhaps more important that we consider how principles of this model may relate to acidndashbase status rather than fully to quantify the SIG Theoretically low albumin and phosphate levels which fre-quently occur in premature infants by reducing the concentra-tion of weak acids can produce a relative alkalosis while high phosphate levels in renal failure may contribute to acidosis
Tissue oxygenation
Oxygenation is closely linked to acidndashbase status as optimal cel-lular function requires oxygen to fuel aerobic metabolism and produce energy In hypoxic conditions anaerobic metabolism predominates which is energy inefficient and results in a lactic acidosis1011
Tissue oxygen availability is related to regional blood flow haemoglobin level and haemoglobin oxygen affinity Arterial blood gases measure the partial pressure of dissolved oxygen (PaO2) which represents a small component of total oxygen con-tent the majority being transported bound to haemoglobin The relationship between percentage haemoglobin saturation (SaO2) and PaO2 is described by the sigmoidal oxyhaemoglobin disso-ciation curve which enables us to relate the two measures to each other235 The affinity of haemoglobin for oxygen is altered by local tissue factors Increases in temperature H+ PaCO2 and 23-diphosphoglycerate (DPG) levels shift the oxyhaemoglobin dissociation curve to the right reducing affinity for oxygen Decreases in temperature H+ PaCO2 and 23-DPG levels shift the curve to the left increasing oxygen affinity1ndash35 In the body haemoglobin oxygen affinity continuously changes increasing in the lungs to enable efficient oxygen uptake and decreasing at tissue level to provide efficient oxygen delivery to metabolically active tissues
Avoiding both hypoxia and hyperoxia is important in the neo-natal unit as deleterious effects of hypoxia are seen in infants with pulmonary hypertension1314 while hyperoxia is associated with an increased incidence of retinopathy of prematurity1516
3 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Clinical acidndashbase imbalances
Clinical acidndashbase imbalances can be respiratory metabolic or a mixture of both These abnormalities may be corrected by the acidndashbase regulatory mechanisms in the body in an attempt to maintain normal pH (Figure 1)
Respiratory acidosisThis occurs when any disorder leads to decreased alveolar ventilation Common causes of respiratory acidosis are listed in Table 1 Reduced respiratory clearance of CO2 means more dissolved CO2 accumulates in the plasma leading to increased production of carbonic acid and H+ Through chemoreceptor stimulation respiratory acidosis rapidly alters ventilation in an attempt to reduce CO226 Chemoreceptor mediated ventila-tory increases may only partly adjust in premature infants with underlying lung disease In babies with a sustained respiratory acidosis eg in chronic lung disease then metabolic compen-sation occurs through increased renal excretion of H+ and reabsorption of HCO3
minus slowly restoring pH to around 80 of normal47
paeDiatRiCS anD CHilD HealtH 184 17
The management of PaCO2 levels in infants receiving mechan-ical ventilation has important clinical implications Premature babies have impaired cerebral autoregulation17 and adverse neurological sequelae are reported in association with high PaCO2 levels18ndash20 Ventilation strategies which advocate lsquoper-missive hypercarbiarsquo have been developed to minimize airways damage from mechanical ventilation21 Published data suggest pulmonary benefits however the safe level of PaCO2 remains to be defined in premature infants2021
Respiratory alkalosisThis occurs when more CO2 is excreted than is produced by the body Pathological conditions leading to respiratory alkalosis are rare Hyperventilation in the neonatal setting is often iatrogenic or may be due to disorders in brainstem control of breathing including hypoxicndashischaemic encephalopathy or primary central nervous system abnormalities (see Table 1)
If respiratory alkalosis is sustained it may be compensated for by reduced reabsorption of filtered bicarbonate Reported adverse associations of low PaCO2 include periventricular leuco-malacia and intraventricular haemorrhage1922
K+
H+
Overventilation
CO2 + H2O harr H2CO3 harr H+ + HCO3ndash
Bicarbonate Buffer
Intracellular Buffer
uarr H+ excretionuarr HCO3
ndash absorption
uarr buffered H+
(NH4+ H2PO4
ndash)uarr ventilation rate
RespiratoryAcidosis
MetabolicAcidosis
darr CO2and uarr pH
RespiratoryAlkalosis
MetabolicAlkalosis
darr H+ anduarr pH
darr ventilation rate
uarrCO2
and darr pH
darr H+ excretiondarr HCO3
ndash absorption
uarrH+ and
darr pH
Brain
Brain
Intracellular Buffer
H+
K+
Sepsis
HypoxiaRDS
Metabolismand growth
Diuretics
Airwayobstruction
Neuromuscularproblems
IEM
Gastric losses
+ +
ndash -
Renal BufferRespiratory Buffer
Figure 1 mechanisms for regulation of extracellular pH iem inborn errors of metabolism RDS respiratory distress syndrome
4 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Common causes of acidndashbase imbalances
pH PCO2 H2CO3 Base excess Common neonatal causes
Respiratory acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
uarr normal normal bull upper airway obstruction choanal atresia
pierre-Robin sequence
bull lung abnormalities respiratory distress
syndrome transient tachypneoa of
newborn pneumonia meconium aspiration
syndrome pulmonary hypoplasia
congenital pulmonary malformations
bull Central hypoventilation hypoxic-ischaemic
encephalopathy intracranial haemorrhage
bull neuromuscular insufficiency congenital
myopathies congenital neuropathies
bull iatrogenic inadequate ventilatory settings
Compensated lower limit
of normal
uarr uarr gt+3
metabolic acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
normal darr ltminus3 increased anion gap
bull lactic acidosis sepsis hypoperfusion
shock necrotizing enterocolitis
bull inorganic acidosis inborn errors of
metabolism renal failure
normal anion gap
bull increased gastrointestinal H2Co3 losses
ileostomy diarrhoea
bull Renal tubular acidoses
Compensated lower limit
of normal
darr darr ltminus3
Respiratory alkalosis Uncompensated gt 745 darr normal normal bull iatrogenic excessive ventilatory settings
bull Compensatory hyperventilation hypoxic-
ischaemic encephalopathy
Compensated higher limit
of normal
darr darr ltminus3
metabolic alkalosis Uncompensated gt 745 normal uarr gt+3 bull gastric losses vomiting non-replacement
of excessive nasogastric aspirates
bull thiazide and loop diuretics
bull Hypokalaemia
Compensated higher limit
of normal
uarr uarr gt+3
Table 1
Metabolic acidosisThis frequently affects infants in the neonatal unit and has many causes1011 (see Table 1) There may be overproduction of tissue acid impaired acid clearance gastrointestinal loss of bicarbonate or an exogenous increased acid load eg chloride total paren-teral nutrition (TPN) or albumin1ndash323
Calculation of the anion gap to distinguish an increased anion gap acidosis from a non-anion gap acidosis is important both for treatment and prognosis1011 Acidosis stimulates respiratory compensation but this is limited in unstable infants Similarly renal compensation with improved HCO3
minus conservation is con-strained by tubular immaturity Treatment of the acidosis should be directed at the underlying cause eg hypoxia hypotension or excess Clminus rather than by administration of base
Metabolic alkalosisThis is unusual in neonates and is most frequently seen in infants with chronic lung disease or heart failure who are receiving diuretics Diuretics cause alkalosis by increasing renal fluid and Na+ losses An active process to reabsorb Na+ occurs in tubule cells which through enhanced H+ secretion and HCO3
minus reab-sorption produce alkalosis27
paeDiatRiCS anD CHilD HealtH 184 17
Metabolic alkalosis may also occur with excessive loss of gas-tric contents eg protracted vomiting or inadequate replacement of nasogastric aspirates (see Table 1)
Interpreting blood gases
Blood gas measurements can provide important diagnostic and prognostic information and a systematic approach to blood gas analysis is described in Table 2 The clinical management of infants with abnormal gases requires a good understanding of acidndashbase physiology and tissue oxygenation and an apprecia-tion of factors which may affect the reliability of samples
Arterial blood sampling is the gold standard however indwelling arterial catheters and arterial stab samples are usually restricted to infants who are critically ill or those who require sig-nificant ongoing intervention Gases are most frequently measured in capillary or venous samples which correlate well with arterial samples for PaCO2 pH and base excess in babies and children receiving intensive care These correlations however are not valid in infants with peripheral vasoconstriction and hypotension2324
Non-invasive monitoring techniques may enable us to reduce the frequency of blood gas sampling Transcutaneous monitoring
5 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
A systematic approach to blood gas analysis
1 Collect the relevant information
bull type of gas ndash capillary or arterial
bull Current respiratory support ndash document level
bull transcutaneous Co2 and Sao2 levels
bull Clarify no significant clinical events before sampling
2 pH accept a range between 730 and 745 in newborn
babies this is lower than in older children is there an
alkalosis (pH gt 745) or an acidosis (lt 730)
3 Co2 aim for a range between 45 and 65 kpa a paCo2 level
more than 65 kpa suggests inadequate alveolar ventilation
while less than 45 kpa suggests hyperventilation Correlate
values with non-invasive measures
4 o2 Can only be assessed from arterial gases aim for pao2
between 60 and 80 kpa Correlate results with pulse
oximetry levels
5 HCo3 and base excess normal HCo3 level is between 20 and
24 mmollitre and bases excess +3 to minus3
6 anion gap look at the anion gap and lactate to help identify
the cause of an acidosis normal lactate levels should be less
than 2 mmollitre
7 Respiratory or metabolic compensation look at the pH and
assess whether it is appropriate for the Co2 level or is there
evidence of compensation
8 interpret use both the clinical history and blood gas
findings to help you identify the primary problem aim your
management at treating the underlying cause
9 Reassess if clinical management changes have been made
repeat the blood gas after an appropriate time interval to
ensure improvement
Table 2
provides a highly accurate and reliable method for measuring PaCO2 through the skin it can however be technically difficult may cause tissue damage and is of limited reliability when peripheral perfusion is reduced25 Continuous end-tidal CO2 measurements correlate well with arterial CO2 values in patients with normal ventilation and perfusion however in babies with lung disease alveolar collapse small tidal volumes and rapid respiratory rates can make these measurements unreliable26 Despite its limitations transcutaneous monitoring provides the best method for CO2 trend monitoring in the neonatal intensive care unit (NICU)25
Oxygen saturation levels can be continuously measured non-invasively using pulse oximetry While oximetry is easy to perform and accurate on occasion SaO2 levels obtained may be unreliable when tissue perfusion is poor or with movement artefact SaO2 monitoring is highly sensitive at detecting hypoxia but is limited in detecting hyperoxia as at levels more than 90 small changes in SaO2 may result in unacceptably large increases in PaO227 It is therefore essential that SaO2 alarm limits are set for all neonates receiving respiratory support to detect hypoxia and prevent hyperoxia1627
Continuous non-invasive monitoring provides invaluable information when managing complex infants in the NICU but it does not replace the need for regular blood gas analysis
paeDiatRiCS anD CHilD HealtH 184 17
ReFeRenCeS
1 Kellum Ja Determinants of blood pH in health and disease
Crit Care 2000 4 6ndash14
2 Quigley R Baum m neonatal acid base balance and disturbances
Semin Perinatol 2004 28 97ndash102
3 Brouillette Rt Waxman DH evaluation of the newbornrsquos blood gas
status Clin Chem 1997 43 215ndash221
4 Chan JC acid-base disorders and the kidney Adv Pediatr 1983 30
401ndash471
5 Siggaard-andersen o the pH-log pCo2 blood acidndashbase nomogram
revised Scand J Lab Invest 1962 14 598ndash604
6 Saetta m mortola Jp interaction of hypoxic and hypercapnic stimuli
on breathing pattern in the newborn rat J Appl Physiol 1987 62
506ndash512
7 Baum m Quigley R postnatal renal development in Seldin DW
giebisch g eds the kidney physiology and pathophysiology new
york lippincott Williams and Wilkins 2000 p 703ndash726
8 ortiz la Quan a Weinberg a et al effect of prenatal
dexamethasone on rat renal development Kidney Int 2001 59
1663ndash1669
9 gabow pa Kaehny WD Fennessey pV goodman Si gross pa
Schrier RW Diagnostic importance of an increased serum anion gap
N Engl J Med 1980 303 854ndash858
10 lorenz Jm Kleinman li markarian K oliver m Fernandez J Serum
anion gap in the differential diagnosis of metabolic acidosis in
critically ill newborns J Pediatr 1999 135 751ndash755
11 Deshpande Sa platt mp association between blood lactate and
acid-base status and mortality in ventilated babies Arch Dis Child
1997 76 F15ndash20
12 Stewart pa modern quantitative acid-base chemistry Can J Physiol
Pharmacol 1983 61 1444ndash1461
13 Dakshinamurti S pathophysiologic mechanisms of persistent
pulmonary hypertension of the newborn Pediatr Pulmonol 2005
39 492ndash503
14 mourani pm ivy DD gao D abman SH pulmonary vascular
effects of inhaled nitric oxide and oxygen tension in
bronchopulmonary dysplasia Am J Respir Crit Care Med 2004
170 1006ndash1013
15 Deulofeut R Critz a adams-Chapman i Sola a avoiding hyperoxia
in infants le 1250 g is associated with improved short- and long-
term outcomes J Perinatol 2006 26 700ndash705
16 Chow lC Wright KW Sola a Can changes in clinical practice
decrease the incidence of severe retinopathy of prematurity in very
low birth weight infants Pediatrics 2003 111 339ndash345
17 Boylan gB young K panerai RB Rennie Jm evans DH Dynamic
cerebral autoregulation in sick newborn infants Pediatr Res 2000
48 12ndash17
18 Kaiser JR gauss CH pont mm Williams DK Hypercapnia during
the first 3 days of life is associated with severe intraventricular
hemorrhage in very low birth weight infants J Perinatol 2006 26
279ndash285
19 Fabres J Carlo Wa phillips V Howard g ambalavanan n Both
extremes of arterial carbon dioxide pressure and the magnitude of
fluctuations in arterial carbon dioxide pressure are associated with
severe intraventricular hemorrhage in preterm infants Pediatrics
2007 119 299ndash305
20 thome uH Carroll W Wu tJ et al outcome of extremely preterm
infants randomized at birth to different paCo2 targets during the
first seven days of life Biol Neonate 2006 90 218ndash225
6 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
21 Carlo Wa Stark aR Wright ll et al minimal ventilation to prevent
bronchopulmonary dysplasia in extremely-low-birth-weight infants
J Pediatr 2002 141 370ndash374
22 okumura a Hayakawa F Kato t et al Hypocarbia in preterm
infants with periventricular leukomalacia the relation between
hypocarbia and mechanical ventilation Pediatrics 2001 107
469ndash475
23 peters o Ryan S matthew l Cheng K lunn J Randomised
controlled trial of acetate in preterm neonates receiving parenteral
nutrition Arch Dis Child 1997 77 F12ndash15
24 yildizda D yapiciolu H yilmaz Hl Sertdemir y Correlation of
simultaneously obtained capillary venous and arterial blood gases
of patients in a paediatric intensive care unit Arch Dis Child 2004
89 176ndash180
25 aliwalas ll noble l nesbitt K et al agreement of carbon
dioxide levels measured by arterial transcutaneous and end tidal
methods in preterm infants 28 weeks gestation J Perinatol 2005
25 26ndash29
26 Hagerty JJ Kleinman me Zurakowski D et al accuracy of a new
low-flow sidestream capnography technology in newborns a pilot
study J Perinatol 2002 22 219ndash225
paeDiatRiCS anD CHilD HealtH 184 17
27 poets CF Wilken m Seidenberg J Southall Dp von der Hardt H
Reliability of a pulse oximeter in the detection of hyperoxemia
J Pediatr 1993 122 87ndash90
Practice points
bull a stable extracellular pH is important for optimal cellular
functioning
bull abnormalities in acidndashbase balance are regulated by buffer
systems and the respiratory and renal tract
bull maintaining a stable pH is challenging for newborn babies
due to their high rates of acid production and immature
regulatory mechanisms
bull arterial or capillary blood gases provide an effective way to
monitor acidndashbase balance in newborns
bull Blood gases should be analysed in a structured manner
assessing pH and then respiratory and metabolic components
bull the treatment of acidndashbase abnormalities should be directed
at the underlying problem not merely at correcting pH
7 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Recognition and management of neonatal seizuresmalcolm levene
AbstractSeizures are the most common major manifestation of central nervous
system dysfunction in the newborn there are many causes but perina-
tal asphyxia and haemorrhagicinfarction lesions account for about 75
there is now considerable evidence that frequent but short seizures in
the neonate affect subsequent neurodevelopmental outcome Studies
using eeg or modified continuous tracing of eeg activity (aeeg or CFm)
have shown that there is often electroconvulsive dissociation this re-
fers to poor correlation between electrical seizures and clinical seizures
Commonly used anticonvulsants appear to increase electroconvulsive
dissociation effective management of neonatal seizures has proved very
disappointing and less than 50 of seizures are abolished by first-line
anticonvulsant medication (phenobarbitone or phenytoin) Drugs such
as midazolam and lidocaine may further reduce seizures but require
more evaluation the challenge is to assess new and more effective anti-
convulsants which are themselves associated with little neurotoxicity
Keywords antiepileptic drugs eeg neonatal seizures neurodegeneration
Convulsions are the most common major neurological sign seen in newborn infants and their incidence estimated from large population studies is 26 per 1000 live births1 Premature infants are over four times more likely to have convulsions than full-term infants12 Neonatal status epilepticus (continuous seizure activity lasting 30 min or more) diagnosed clinically is rare and accounts for only 5 of infants with seizures1 although this is now recognized more frequently as the result of continuous EEG monitoring3
Neonatal convulsions are described as presenting in a num-ber of different ways and various seizure types can be seen in the same baby over a number of hours The frequencies of the various patterns of seizure activity are given in Table 1 In very premature babies and to a lesser extent in term infants minor movement abnormalities may be difficult to identify as subtle seizures These include lip smacking tongue thrusting mouth-ing pedalling type movements of the lower limbs or swimming movements of the arms Apnoea can be a common manifesta-tion of subtle seizures The signs can be protean and vary from baby to baby or even in the same baby Virtually any stereotypic
Malcolm Levene MD FMedSc FRCPCH FRCH is Professor and Head of
Department of Paediatrics and Child Health at University of Leeds Leeds
and Honorary Neonatologist at Leeds General Infirmary Leeds UK
paeDiatRiCS anD CHilD HealtH 184 178
movement may be a manifestation of a seizure disorder in the newborn
Aetiology
The more carefully the fitting baby is investigated the more likely it is that a cause for the seizures will be found A number of recent papers have described the aetiology of neonatal con-vulsions after extensive investigations14 Tekgul et al4 recently studied a consecutive group of full-term infants with evidence of neonatal convulsions (recognized both clinically and on EEG) and reported their outcome Table 2 summarizes these data as well as risk of moderate or severe disability for each causative factor Perinatal asphyxia is the commonest cause for convul-sions in term infants with haemorrhagic or ischaemic lesions also being common
Overall the prognosis for the group of term babies with con-vulsions was good 72 had a favourable outcome Where asphyxia (hypoxicndashischaemic insult) is the cause of neonatal convulsions the outcome is poor in 50 The prognosis for neonatal convulsions when they were due to arterial or cere-brovenous infarction or intracranial haemorrhage was generally good Individually inborn errors are a very rare cause of neo-natal convulsions but in view of the treatable nature of some of these it is essential that these be considered and investigated appropriately5
Patterns of seizure activity in the newborn
Movement pattern Frequency ()
Clonic 50
tonic 20
Subtle 10ndash35 depending on maturity
myoclonic 5
Table 1
Cause incidence and outcome of neonatal convulsions in term infants14
Aetiological factor Incidence () Poor outcome ()
asphyxia 38ndash40 50
Cerebral arteriovenous
infarction
20 0
intracranial haemorrhage 12ndash20 13
Congenital cerebral anomaly 5ndash10 100
Hypoglycaemiahypocalcaemia 3ndash19
infection 3ndash20
inborn error of metabolism 1
unknown cause 10ndash13 0
Refers to moderate and severe neurodevelopmental abnormalitynumbers too small to make meaningful predictions
Table 2
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Controversies in the clinical management of neonatal seizures
In recent years we have learnt much more about the neurobi-ology of seizures and their effect on the developing brain The neonatal brain is in a neurophysiologically hyperexcitable state compared to the more mature brain and therefore is more prone to seizure activity This is due largely to a relative excess of GABA neuroreceptors GABA receptors are usually inhibitory but in the immature brain they have a paradoxically excitatory effect This changes at about term in primates and with progressive develop-ment they adopt a neuroinhibitory role6
The propensity to seizures in the neonatal brain makes resolv-ing the balance of risks between continuing seizure activity on the one hand against potentially adverse effects of therapy on the other a very important equation Added to this is the problem of accurately diagnosing neonatal seizures and whether commonly used anticonvulsants are successful in controlling them
These conundrums can be posed as a series of challenging questions which are discussed below
Do neonatal convulsions cause brain injuryConvulsions are a sign of neurological compromise and may indi-cate significant underlying structural brain damage or biochemi-cal disturbance which may cause further brain damage in its own right There has been considerable debate about the scale of the disability that convulsions cause the immature brain over and above that due to the underlying cause Most of our knowledge comes from studies in rodents and these have provided some tentative answers to this question
Seizures in the mature brain lead to neuronal necrosis but studies in very young rat pups whose brain development is somewhat similar to full-term infants have shown that a series of five brief seizures on five successive days does not cause struc-tural neuronal damage but does produce morphological changes in hippocampal neurones and worryingly deficits in the rat learning and visual spatial memory function in adolescent and adult life7 A single prolonged neonatal convulsion in similarly immature rats does not produce any functional effects8 Others have shown that following priming of the neonatal rat brain by short seizures as described above a further insult comprising induction of status epilepticus in the same rats at an older age causes neuronal necrosis9 This has been referred to as the lsquotwo hit hypothesisrsquo10
A more specific question is does seizure activity in an already significantly compromised brain cause additional neuropathol-ogy Wirrell et al11 studied a series of immature rat pups with the induction of an hypoxicndashischaemic (asphyxial) insult fol-lowed by either chemically-induced fits or a control sham pro-cedure In the more severely asphyxiated animals the degree of brain damage was increased significantly in those that had the additional burden of induced seizures
In summary these studies show that the immature brain is more resistant to short frequent post-seizure damage than the mature brain but despite resulting in no loss of neuronal numbers the function of the brain is permanently affected in later life In the asphyxiated brain seizures appear to have an additional adverse effect on brain damage Furthermore the immature brain that has been lsquoprimedrsquo by early seizures is more
paeDiatRiCS anD CHilD HealtH 184 179
vulnerable to status epilepticus later in life It would appear from these data that frequent seizures in the human infant should be stopped and this begs the question as to whether currently used anticonvulsants effectively control neonatal seizures
Can we rely on clinical versus EEG diagnosis of neonatal convulsionsTraditionally the diagnosis of neonatal convulsions has been made by observation and description of the frequency of abnor-mal movements EEG has been technically difficult in the hostile electrical activity of a neonatal intensive care environment and considerable expertise is required for analysis of the trace It is usually not practical to undertake traditional EEG recordings at the time the baby shows abnormal movements More recently various technological developments have allowed more direct investigation of neuronal electrical activity by either video-EEG or compressed recording of the amplitude integrated EEG (aEEG or CFM)
Rennie et al3 at Kingrsquos College Hospital London have under-taken extensive evaluation of video-EEG and have found that this technique detects many convulsions not recognized by a single channel aEEG or CFM trace Of 19 infants with evidence of convulsions on EEG only four were recognized on CFM but this may have been due to the observersrsquo lack of experi-ence with this technique In other centres that have developed appropriate expertise aEEG or CFM has proved more sensitive to the detection of seizures Video-EEG studies have also shown that many movements interpreted by experienced clinicians to be seizures are not associated with abnormal cortical activity Conversely many electrical seizures are not associated with abnormal movements This is referred to as electroconvulsive dissociation
In summary clinical observation alone to detect the fitting baby is unreliable in that it may either over-detect seizure activ-ity which is not present on EEG or under-detect clinical seizures in infants with EEG-proven convulsions The decision as to which babies to treat with antiepileptic drugs therefore becomes somewhat arbitrary
Do anticonvulsants stop neonatal seizuresAlthough neonatal seizures are common there are few random-ized controlled trials assessing the benefits of antiepileptic drugs (AEDs) in the treatment of this condition Phenobarbitone is the most widely used first-line AED and in an Australasian study 95 of neonatologists and paediatric neurologists used this drug as first-line management12 The most commonly used loading dosage is 20 mgkg but regimens of up to 40 mgkg have been recommended (Table 3)13 Four trials have evaluated the effect of phenobarbitone in abolishing neonatal seizures Two of these studies used EEG to monitor response to the drug1415 and one compared phenobarbitone with phenytoin15 In the latter study seizures were completely controlled in only 43 of babies and in the group where phenytoin was the first drug used com-plete seizure control was achieved in 45 This study switched babies from their first AED to the other if complete control was not obtained on EEG monitoring after exposure to first-line therapy In babies who had been given phenobarbitone as first-line therapy seizure control was only achieved in 57 after phenytoin was added In those given phenytoin first complete
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Dosage regimens for first- second- and third-line anticonvulsants in the neonatal period
Loading dose Second loading dose if first
unsuccessfulMaintenance dose
phenobarbitone 20 mgkg by slow iv injection 10 mgkg iv 25ndash5 mgkg od
phenytoin 20 mgkg iv over 20 min not recommended
midazolam 150ndash200 μgkg iv infusion 1 μgkgmin iv infusion increasing to 5 μgkgmin
until favourable response
lidocaine 2 mgkg iv over 10 min 6 mgkgh for 6 h iv then 4 mgkgh for 12 h then
2 mgkgh for 12 h
lorazepam 005ndash01 mgkg by slow iv injection
Diazepam 03ndash04 mgkg iv over 3ndash5 min
lidocaine should not be used if the infant has previously been treated with phenytoin
Table 3
seizure control was achieved with the adding of phenobarbitone in 62
Boylan et al14 assessed the efficacy of phenobarbitone (20ndash40 mgkg iv over 20 min) in 14 babies monitored by video-EEG in only four was there complete abolition of seizures and in the other 10 electroconvulsive seizure activity increased whereas clinical evidence of seizures reduced This has been termed elec-troclinical dissociation and anticonvulsant drug use in the new-born appears to increase this feature They also showed that the babies least likely to respond to the first-line AED are those with the most abnormal background EEG
Two studies have evaluated the use of phenobarbitone in babies who had sustained significant asphyxial insult at birth Hall et al13 compared high-dose phenobarbitone (mean 39 mgkg) versus standard dose (27 mgkg) and reported fewer convul-sions and a significant reduction of severe disability or death in the high dose group (RR 030 CI 010ndash093) A recent study from India16 of babies with hypoxicndashischaemic encephalopathy ran-domized 25 babies to phenobarbitone (20 mgkg loading dose) and compared them with 20 control babies Only 2 of 25 (4) in the phenobarbitone group developed convulsions compared with 8 of 20 (40) in the control group (p = 001) Because of the specific enrolment criteria (asphyxial insult) neither of these studies is strictly comparable to the studies by Painter et al15 and Boylan et al14 whose intention was to assess the efficacy of first-line anticonvulsant therapy on convulsions of any cause diagnosed either clinically or by EEG
Other anticonvulsants used as second- and third-line drugs have been subject to few studies in the newborn Midazolam is administered as a bolus followed by continuous infusion A recent study17 has shown that in 10 of 13 neonates given intravenous midazolam for status epilepticus control of electri-cal seizures was achieved within the first hour of treatment having been previously shown to be refractory to phenobarbi-tone treatment Some of these babies required a second bolus infusion of midazolam to obtain control of all electrographic seizures
In some parts of Europe lidocaine is used as a third-line anti-convulsant Malingre et al18 evaluated 20 infants refractory to
paeDiatRiCS anD CHilD HealtH 184 180
both phenobarbitone and midazolam and who were then given lidocaine by continuous infusion Lidocaine was effective in abolishing electroconvulsive seizures diagnosed by aEEG in 76 of the treatment courses studied No babies developed cardiac arrhythmias a previously reported complication of lidocaine in older patients As a result of pharmacokinetic studies the dosage regimen has been modified (see Table 3)
In summary phenobarbitone is effective in seizure control in less than 50 of babies and even when combined with phe-nytoin the efficacy of these drugs together remains poor More worrying is the observation that phenobarbitone tends to reduce clinically evident seizures thereby giving the clinician a false sense of security whilst having little or no effect on the num-bers of electroconvulsive disorders This has been summarized appropriately as lsquoafter all these years we still love what doesnrsquot workrsquo19 Both midazolam and lidocaine infusions appear to be effective in abolishing severe seizures in some infants resistant to phenobarbitone Lidocaine should not be given to babies previ-ously exposed to phenytoin for fear of a synergistic adverse effect on cardiac rhythm
Do antiepileptic drugs cause brain damageA riskndashbenefit analysis is needed to evaluate the efficacy of anticonvulsants in stopping neonatal seizures which is poor with standard anticonvulsants as discussed above against the risk of administering the anticonvulsant drugs themselves Phenobarbitone has been reported to have adverse effects on the developing brain including inhibition of brain growth20 neuronal toxicity21 and adverse behavioural and cognitive effects into adult life when administered to young animals22 Phenytoin shows unpredictable plasma levels and potential cardiotoxicity
Recent studies have shown an effect of AED exposure on the developing brain by causing neurodegeneration23 Phenytoin administration to immature rat pups at doses which produce serum levels similar to those achieved in human neonates was associated with widespread neuronal death as a result of apop-tosis (programmed cell death) Phenobarbitone had a similar effect when a dosage regimen similar to 40 mgkg was used and
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
this effect was maximal in the more immature brain Diazepam and clonazepam also resulted in a similar effect Midazolam and lidocaine were not tested in this study The combination of phenobarbitone or phenytoin with diazepam had a particularly profound effect on neurodegeneration
In summary recent data suggest that the commonly used AEDs for neonatal convulsions may in themselves cause neuro-degeneration due to apoptosis with lasting effects on develop-ment Many babies with neonatal convulsions are treated with at least two AEDs and this may produce more severe adverse effects than the seizures themselves
Practical management of neonatal seizures
Assimilation of these data and formulation of a rational policy is difficult when faced with a fitting neonate on an intensive care unit and pressure on the medical staff to lsquodo somethingrsquo but it is important to accept that sometimes doing nothing is preferable to using potentially dangerous drugs in a situation which does not warrant such intervention Many babies who have normal interseizure neurological clinical findings and whose seizures are relatively brief and infrequent probably do not need anticon-vulsant medication A normal or near-normal background EEG trace should reassure the clinician that anticonvulsants can be withheld
Some causes of neonatal convulsions are treatable such as meningitis hypoglycaemia hypocalcaemia and inborn errors of metabolism and each baby should be rapidly and carefully investigated for cause of the convulsions
In some babies clinical assessment of seizures is difficult ie when the baby is very sick small or paralyzed Sometimes it may be difficult to assess the significance of certain movement pat-terns Under these circumstances an EEG may prove to be very helpful In many units EEG is not available out of hours and a simple aEEG or CFM is strongly advised Modern instruments are very simple to apply and prolonged or frequent seizures should be identified with only moderate training The printout can be faxed to a more senior doctor if there is doubt as to what is shown on the trace
The balance of knowledge now is that frequent seizures cause additional damage to the developing brain and that treatment to abolish the seizures is warranted Unfortunately there is little evidence that the majority of seizures can be effectively termi-nated by current standard therapy Furthermore it appears that the more abnormal the background EEG the more difficult it is to control the seizures Nevertheless a written protocol for the management of neonatal convulsions is required on each unit Phenobarbitone and phenytoin remain the mainstay of treat-ment although their effectiveness is disappointing There is little to suggest that midazolam is more effective than lidocaine as third-line therapy but lidocaine is precluded if phenytoin has been previously used
In view of the anxiety as to the neurodegenerative effects on the immature brain of most anticonvulsants used in the neonatal period (particularly when multiple drugs are used) it is prefer-able to use only one drug to maximum dosage before introduc-ing a second In addition the duration of anticonvulsants should be minimized and the drugs stopped at the earliest opportu-nity It is my practice to stop anticonvulsants prior to discharge
paeDiatRiCS anD CHilD HealtH 184 18
from hospital if the baby is neurologically normal on clinical examination
REFEREnCES
1 Ronen gm penney S andrews W the epidemiology of clinical
neonatal seizures in newfoundland a population-based study
J Pediatr 1999 134 71ndash75
2 lanska mJ lanska DJ Baumann RJ et al a population-based study
of neonatal seizures in Fayette County Kentucky Neurology 1995
45 724ndash732
3 Rennie Jm Chorley g Boylan gB et al non-expert use of the
cerebral function monitor for neonatal seizure detection Arch Dis
Child Fetal Neonatal Ed 2004 89 F37ndashF40
4 tekgul H gauvreau K Soul J et al the current etoliologic profile
and neurodevelopmental outcome of seizures in term newborn
infants Pediatrics 2006 117 1270ndash1280
5 Surtees R Wolf n treatable neonatal epilepsy Arch Dis Child 2007
92 659ndash661
6 Ben-ari y Holmes gl effects of seizures on developmental
processes in the immature brain Lancet Neurol 2006 5 1055ndash
1063
7 Holmes gl gairsa Jl Chevassus-au-louis n et al Consequences of
neonatal seizures in the rat morphological and behavioral effects
Ann Neurol 1998 44 845ndash857
8 Stafstrom Ce Chronopoulos a thurber S et al age-dependent
cognitive and behavioural deficits following kainic-acid inducing
seizures Epilepsia 1993 34 420ndash432
9 Schmid R tandon p Stafstrom Ce et al effects of neonatal seizures
on subsequent seizure-induced brain injury Neurology 1999 53
1754ndash1761
10 Hoffmann aF Zhao Q Holmes gl Cognitive impairment following
status epilepticus and recurrent seizures during early development
support for the ldquotwo-hit hypothesisrdquo Epilepsy Behav 2004 5
873ndash877
11 Wirrell eC armstrong ea osman lD et al prolonged seizures
exacerbate perinatal hypoxic-ischemic brain damage Pediatr Res
2001 50 445ndash454
12 Carmo KB Barr p Drug treatment of neonatal seizures by
neonatologists and paediatric neurologists J Paediatr Child Health
2005 41 313ndash316
13 Hall Rt Hall FK Daily DK High-dose phenobarbital therapy in term
newborn infants with severe perinatal asphyxia a randomized
prospective study with three-year follow-up J Pediatr 1998 132
345ndash348
14 Boylan gB Rennie Jm pressler Rm et al phenobarbitone neonatal
seizures and video-eeg Arch Dis Child Fetal Neonatal Ed 2002 86
F165ndash170
15 painter mJ Scher mS Stein aD et al phenobarbital compared with
phenytoin for the treatment of neonatal seizures N Engl J Med
1999 341 485ndash489
16 Singh D Kumar p narang a a randomized controlled trial of
phenobarbital in neonates with hypoxic ischemic encephalopathy
J Matern Fetal Neonatal Med 2005 18 391ndash395
17 Castro Conde JR Borges H Domenech martinez e et al midazolam
in neonatal seizures with no response to phenobarbital Neurology
2005 64 876ndash879
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
18 malingre mm Van Rooij lgm Rademaker Cma et al Development
of an optimal lidocaine infusion strategy for neonatal seizures Eur
J Pediatr 2006 165 598ndash604
19 Sankar R painter mJ neonatal seizures after all these years we still
love what doesnrsquot work Neurology 2005 64 776ndash777
20 Diaz J Schain J Bailey Bg phenobarbital-induced brain growth
retardation in artificially reared rat pups Biol Neonate 1977 32 77ndash82
21 mattson RH phenobarbital toxicity in levy RH Dreifuss Fe
mattson RH et al eds antiepipeptic Drugs 3rd edn new york
Raven 1985 p 341ndash355
22 mikati ma Holmes gl Chronopoulos a et al phenobarbital
modifies seizure-related brain injury in the developing brain Ann
Neurol 1994 36 425ndash453
23 Bittigau p Sifringer m genz K et al antiepileptic drugs and
apoptotic neurodegeneration in the developing brain Proc Natl
Acad Sci U S A 2002 99 15089ndash15094
paeDiatRiCS anD CHilD HealtH 184 182
Practice points
bull the clinician needs to be aware that almost any repetitive
stereotype movement pattern can be a manifestation of
neonatal seizures
bull eeg is important in defining neonatal seizures
bull Frequent short-lived seizures have been shown to cause long-
term neurodevelopmental problems
bull Conventional anticonvulsant medication is ineffective in
abolishing neonatal seizures in greater than 50 of cases
bull there is evidence that exposure of the neonatal brain to
multiple anticonvulsants causes neuronal death
bull Future research is needed to evaluate more effective
anticonvulsants for treating this condition
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
Emotional support for families of sick neonatesMarina nicolaou
cristine Glazebrook
AbstractParents of sick neonates experience high levels of stress anxiety and
depression Most interventions with families of sick infants have focused
on fostering the motherndashinfant relationship through the provision of
information about infant developmental needs or through increased
motherndashinfant contact Many of these studies have reported improved
maternal well-being though there are some concerns about the scope
and practicality of large-scale interventions The few studies to have
prioritized emotional support for parents of sick neonates have pro-
duced encouraging results even interventions requiring relatively few re-
sources such as telephone support parent-to-parent support and group
support have been associated with reduced psychological morbidity for
parents The needs of parents can change throughout their infantrsquos hos-
pitalization and not all want or benefit from the provision of additional
support Thus neonatal intensive care units should aim to provide a
varied flexible and sustainable programme of support options Further
research should focus on the needs of fathers
Keywords mental health neonatal intensive care parents
The admission of an infant to neonatal care is acknowledged to be a source of considerable distress for families This review aims to explore evidence for the psychological impact on families of having an infant in neonatal intensive care and to identify evi-dence for the effectiveness of interventions to promote parental well-being It will conclude with recommendations for strategies to support parents of vulnerable infants and suggestions for fur-ther research
Psychological impact of neonatal care for parents
The majority of research examining the effect on parents of having a sick neonate has focused on families of premature or low birthweight infants Such research has found that parents with a sick neonate exhibit high levels of stress compared to normative samples and to parents of healthy full-term infants1 Singer et al2 examined the stress experienced by mothers of high-risk very low birthweight (VLBW) low-risk VLBW and term
Marina Nicolaou MPhil is a Teaching Assistant at the School of
Community Health Sciences University of Nottingham Nottingham UK
Cristine Glazebrook PhD is a Professor of Health Psychology at the School
of Community Health Sciences University of Nottingham Nottingham UK
PaeDiaTrics anD cHilD HealTH 184 196
infants Several self-report measures were used including the Brief Symptom Inventory the Parenting Stress Index (PSI) the Impact on Family Scale and the Family Inventory of Life Events and Changes (FILE) Mothers of VLBW infants had more psycho-logical distress at 1 month compared to mothers of term infants Mothers of high-risk VLBW infants also reported high psycho-logical distress at 2 years and high levels of parenting stress at 3 years Mothers have also been found to have higher stress levels compared to fathers Shaw et al3 examined the prevalence of acute stress disorder (ASD) in 40 parents whose infants were in the neonatal intensive care unit (NICU) Nearly half of the moth-ers (44) met the criteria for ASD although none of the fathers did Furthermore the severity of the symptoms (measured by the number of concurrent symptoms) was greater for the moth-ers than for the fathers3 The reasons behind this difference have been widely speculated with some believing that it is due to the mothersrsquo greater psychological involvement with the infant as evidenced by their general greater vulnerability to postpartum psychological disorder It could also reflect gender differences in coping style
Having an infant who requires intensive medical care repre-sents a significant emotional burden for families Not only is there extreme anxiety surrounding the infantrsquos health and distress for the childrsquos suffering there is also the unfamiliar and intimidating environment of the NICU to adjust to Hopper in her review of the literature identified sources of stress for parents of sick neo-nates as falling into three areas4 Situational factors included the severity of the infantrsquos illness and how parents adapted to the life crisis of having a sick infant Personal factors involved parental emotions about their roles and the instrumental and informa-tional support which were available to them The third area was classified as environmental sources of stress and included the environment of the NICU and the relationship between parents and members of staff This relationship has been examined by several studies in the nursing literature nurses are seen as ide-ally placed to provide the necessary support and information to parents with sick neonates However whilst some studies have shown that supportive and helpful hospital staff can have a posi-tive effect on parents other studies have highlighted the prob-lems and difficulties which can manifest It has been shown that parents and nurses often have very different ideas about issues eg the necessary skills and competencies needed in an NICU or the characteristics that make a lsquogood motherrsquo
Research has shown that there may be a relationship between high levels of parental stress and an increased likelihood of depression5 Postpartum depression is a psychiatric illness which appears in 10ndash15 of postpartum women Its reported preva-lence rates however have ranged from less than 10 up to 306 depending on the instruments used the population exam-ined and the timing of the research Several factors have been found to be associated with postpartum depression including poor social support and infant-related stressors6 Evidence indi-cates that postnatal depression may be underreported and this is of concern since the mental and psychological health of the mother can affect her relationship with her infant and thus the infantrsquos cognitive and emotional development5 Depressed moth-ers appear to look touch and talk to their infants less frequently and also appear to show fewer positive and more negative faces7 The vocalizations of mothers suffering with depression have also
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
been found to be less effective at promoting cognitive growth and learning in infants8
If researchers are interested in finding ways of providing sup-port for families of sick neonates then they must listen to what such families perceive their needs to be in order to avoid increas-ing anxiety and distress Furthermore the provision of appropri-ate support be it emotional informational or social will enhance parental coping abilities increase self-esteem and reduce anxiety It should be noted though that the research conducted around these issues has often taken lsquosupport needsrsquo as being synony-mous with lsquoinformation needsrsquo Such studies have examined the type the amount and quality of information that parents receive and perceive themselves as needing but have not explored in equal depth the perceived emotional support needs of families who have a sick infant In addition the needs of parents may change throughout their infantrsquos illness Ward examined the per-ceived needs of 52 parents of infants in an NICU9 Parents rated the needs of their hospitalized infant as most important along with the need to be reassured Interestingly they ranked their support needs as least important This research was conducted during the first week of the infantsrsquo hospitalization however which would explain the preoccupation of the parents with the infantrsquos health These results demonstrate that if researchers want to find ways of providing emotional support to parents of sick neonates they must be prepared not only to listen to parents but also to be flexible enough to satisfy the parentsrsquo changing needs and expectations
Interventions aimed at supporting parents
Most interventions that been evaluated in controlled studies have focused on supporting the motherndashinfant relationship and provid-ing information on infant development Many of these interven-tions have included the aim of improving the parental emotional state and thus psychological outcomes such as stress or anxi-ety have been assessed However few studies appear to include fathers This means that strategies implemented to provide emo-tional support to families of sick neonates are often derived from interventions tailored for mothers even though fathers may have different emotional needs
A wide range of interventions with mothers and infants has been evaluated in the NICU Increasing motherndashinfant contact through kangaroo care has been found to reduce maternal anxiety1011 and educational programmes delivered to fami-lies in the NICU have also been associated with reduced emo-tional difficulties in parents12ndash14 Kaaresen and colleagues implemented an intervention which consisted of eight sessions before discharge and four home visits all by trained nurses The sample included 71 premature infants in the intervention group 69 premature infants in the control group and 74 infants in the full-term control group The randomized controlled trial found that the intervention reduced parenting stress in both mothers and fathers of premature infants compared to controls to a level equivalent to parents in the term control group13 At 6 months corrected age mothers of preterm infants who had not received the intervention had total PSI scores which were 17 points higher than the mothers of infants born at term (an effect size of 057) A similar study evaluated the efficacy of an educationalndashbehavioural programmendashCreating Opportunities for
PaeDiaTrics anD cHilD HealTH 184 19
Parent Empowerment (COPE) ndash through a randomized controlled trial with 260 families of premature infants14 COPE was a four-phase educationalndashbehavioural programme which began as early as 2ndash4 d after mothers had given birth and continued until 1 week after discharge from the NICU The programme consisted of audiotaped and written infant behaviour information along with photographs which focused on common behaviours and characteristics of premature infants It also included various par-ent activities in the form of a four-phase workbook which aimed to assist mothers in the implementation of the experimental infor-mation COPE was found significantly to reduce maternal stress in the NICU as well as maternal anxiety and depressive symptoms after hospitalization In contrast a cluster randomized trial of a parenting intervention delivered to mothers of very premature infants from soon after birth showed no benefits for parenting stress1 The authors hypothesized that the intervention had not been of sufficient intensity particularly in the weeks surrounding discharge Neonatal care presents a significant barrier to parent-ing in the early weeks following a very preterm birth and so inter-ventions which focus on the developmental needs of infants and the parentndashchild relationship should particularly aim to support parents as they take on the parenting role There was also concern that the intervention had failed to reach those most at risk
Since large-scale projects can be costly to implement and may often fail to reach the families in most need it may be wiser to focus on intervention programmes which are more practical and easier to implement within a neonatal care setting Research has shown that even interventions which are based on one-off meet-ings with parents of sick neonates can be effective Jotzo and Poets examined the effect of an intervention programme aimed at reducing the severity of traumatic responses as a result of giv-ing birth prematurely15 Their programme consisted of a one-off intervention meeting along with additional psychological help throughout the hospitalization of the infant The meeting cov-ered a variety of issues including a reconstruction of the events shortly before and after the infantrsquos birth relaxation techniques discussion of coping strategies available resources and social support and support during emotional outbursts The measures used included the Impact of Event Scale (IES) and the Peritrau-matic Dissociative Experience Questionnaire At discharge the mothers who received the intervention were found to have a significantly lower traumatic impact as a result of premature birth Furthermore fewer mothers in the intervention group showed symptoms of clinically significant psychological trauma at discharge compared to mothers in the control group (36 vs 76)15 The lsquoParents Circle Programrsquo is another intervention with a similar structure16 This consisted of a 90 min session for parents with the aim of enhancing the developing relationship between parents and infants and to offer parents support A total of 104 parents (59 mothers and 45 fathers) and 44 members of hospital staff were asked to evaluate the programme and their results were analysed using content analysis Families reported gaining perspective on their situation feeling supported becom-ing aware of cues and optimizing interactions and becoming aware of available resources Parents and staff alike felt that participating in the intervention helped parents overcome the difficulties associated with the early time of their infantrsquos hos-pitalization Additional studies have also found positive results with fairly minimal interventions including discussion groups
7 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
in the NICU music during kangaroo care and pairing mothers of sick neonates with trained mothers who had been through similar experiences
Parent support programmes
Parent support programmes (PSPs) which are based in NICUs can provide parents with the opportunity to talk to parents who have been in similar situations and also to discuss their emo-tions with professionals who can help them cope with their situa-tion111718 The parent-to-parent support programme for mothers of preterm infants evaluated by Preyde and Ardal included edu-cational parental support group meetings and individual par-ent-to-parent support (primarily telephone support)19 Measures used included the Parental Stressor Scale NICU the State and the Trait Anxiety Inventories and the Beck Depression Inven-tory After 4 months of participation mothers in the intervention group reported lower levels of stress state anxiety and depres-sion compared to control group mothers The authors speculated however that the participants who were able to meet face to face with other parents were those who benefited the most Hurst conducted a comprehensive survey of an NICU-based PSP This PSP was provided in a variety of formats including a weekly parent support group hospital visitation and 24-h telephone sup-port20 Of the 477 participants 303 families used the PSP dur-ing a 2-year evaluation period with 78 using only one form of support and 18 using two forms Of a sub-sample of 48 parents asked to complete an evaluation of the PSP 92 stated that they would recommend such a programme to other parents Furthermore the majority of parents felt that it made them feel supported and helped them deal with their emotions20 This is an indication that such programmes can be very successful in sup-porting parents throughout their infantrsquos hospitalization It also shows that it can be beneficial to give parents several options and formats when it comes to such support services It is impor-tant to consider though that both the Hurst and the Preyde and Ardal studies found that some participants did not find the sup-port programmes helpful even reporting that they had caused them increased stress and anxiety Therefore it should not be assumed that support programmes will suit every individual and will provide the required support for all parents1920 NICUs need to be flexible enough to provide parents with a range of forms of support to choose from
The increased understanding of the strains that parents of sick neonates have to deal with has also led to efforts to improve customary practices in NICUs Family-centred care focuses on infants and their needs and attempts to redefine the relationship between parents and caregivers These practices strive to provide parents with support during their infantrsquos illness by focusing on freely sharing information and on the collaboration between parents and hospital staff Family-centred care has been found to be associated with several beneficial outcomes including improved parental satisfaction increased parental comfort staff satisfaction and decreased parental stress18 Research is already examining these practices and questioning how these can be improved further Such research reflects the increasing effort focused on lsquohumanizingrsquo the environment in NICUs in order to make parents feel more comfortable about spending time with their infants
PaeDiaTrics anD cHilD HealTH 184 19
Conclusion
Surprisingly few interventions have prioritized the provision of emotional support for parents of sick neonates or accounted for the changing needs and wishes of parents over the course of their infantrsquos care Large-scale supportive education-based inter-ventions have been shown to be effective in reducing parental distress However the feasibility and sustainability of such pro-grammes should also be considered Programmes which require significant additional resources can be expensive and there are also issues of training and quality control Interventions which require significant input from parents may also place additional burdens on families making them potentially less accessible to those most at risk Arguably the aim should be to explore ways of providing acceptable and effective informational support which could be complemented by emotional support from health professionals and from other parents in the unit Increasingly studies are exploring the use of computers and multimedia as an engaging flexible and cost-effective method of targeting indi-vidual needs and providing support and information Such com-puter-based and interactive multimedia interventions have been found to be successful with a range of patient groups and could therefore be examined as a complementary method of providing informational support to families with sick neonates
REfEREnCEs
1 Glazebrook c Marlow n israel c et al randomised trial of a
parenting intervention during neonatal intensive care Arch Dis Child
Fetal Neonatal Ed 2007 92 F438ndash443
2 singer lT salvator a Guo s collin M lilien l Baley J Maternal
psychological distress and parenting stress after the birth of a very
low-birth-weight infant JAMA 1999 281 799ndash805
3 shaw rJ Deblois T ikuta l Ginzburg K Fleisher B Koopman c
acute stress disorder among parents of infants in the neonatal
intensive care nursery Psychosomatics 2006 47 206ndash212
4 Hopper a sources of stress for parents of a sick neonate a
literature review Pediatr Nurs 2000 30 29ndash32
5 Davis l edwards H Mohay H wollin J The impact of very
premature birth on the psychological health of mothers Early Hum
Dev 2003 73 61ndash70
6 Bernazzani O saucier J-F David H Borgeat F Psychosocial
predictors of depressive symptomatology level in postpartum
women J Affect Disord 1997 46 39ndash49
7 Field T infants of depressed mothers Infant Behav Dev 1995 18
1ndash13
8 Kaplan Ps Bachorowski J-a Zarlengo-strouse P child-directed
speech produced by mothers with symptoms of depression fails
to promote associative learning in 4-month-old infants Child Dev
1999 70 560ndash570
9 ward K Perceived needs of parents of critically ill infants in
a neonatal intensive care unit (nicU) Pediatr Nurs 2001 27
281ndash286
10 lai Hl chen cJ Peng Tc et al randomized controlled trial of music
during kangaroo care on maternal state anxiety and preterm infantsrsquo
responses Int J Nurs Stud 2006 43 139ndash146
8 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
11 Tallandini Ma scalembra c Kangaroo mother care and mother-
premature infant dyadic interaction Infant Ment Health J 2006 27
251ndash275
12 Ohgi s Fukuda M akiyama T Gima H effect of an early intervention
programme on low birthweight infants with cerebral injuries
J Paediatr Child Health 2004 40 689ndash695
13 Kaaresen Pi ronning Ja Ulvund se Dahl lB a randomized
controlled trial of the effectiveness of an early-intervention program
in reducing parenting stress after preterm birth Pediatrics 2006
118 e9ndash19
14 Melnyk BM Feinstein nF alpert-Gillis l et al reducing premature
infantsrsquo length of stay and improving parentsrsquo mental health
outcomes with the creating opportunities for parent empowerment
(cOPe) neonatal intensive care unit program a randomized
controlled trial Pediatrics 2006 118 e1414ndash1427
15 Jotzo M Poets cF Helping parents cope with the trauma of
premature birth an evaluation of a trauma-preventive psychological
intervention Pediatrics 2005 115 915ndash919
16 Pearson J andersen K evaluation of a program to promote positive
parenting in the neonatal intensive care unit Neonatal Netw 2001
20 43ndash48
17 roman l lindsay J Boger r et al Parent-to-parent support
initiated in the neonatal intensive care unit Res Nurs Health 1995
18 385ndash394
18 Meyer ec coll cTG lester BM Boukydis cFZ McDonough sM Oh w
Family-based intervention improves maternal psychological well-
being and feeding interaction of preterm infants Pediatrics 1994
93 241ndash246
PaeDiaTrics anD cHilD HealTH 184 19
19 Preyde M ardal F effectiveness of a parent ldquobuddyrdquo program for
mothers of very preterm infants in a neonatal intensive care unit
CMAJ 2003 168 969ndash973
20 Hurst i One size does not fit all Parentsrsquo evaluations of a support
program in a newborn intensive care nursery J Perinat Neonatal
Nurs 2006 20 252ndash261
Practice points
bull Parents of sick neonates experience significant distress and
exhibit higher levels of stress anxiety and depression than
parents of healthy infants
bull educational support emotional support and increased
motherndashinfant contact have been shown to promote maternal
well-being
bull emotional support for fathers has been largely neglected in
the research literature
bull Parents benefit from a choice of supportive facilities which
could include face-to-face sessions with health professionals
telephone support hospital visitation parent-to-parent
support and unit-based group support meetings
bull Parentsrsquo support needs can change during their infantrsquos
hospitalization and not all parents want or benefit from the
provision of additional information and emotional support in
the neonatal unit
9 copy 2008 elsevier ltd all rights reserved
Personal Practice
When should enteral feeds be started in preterm infantsnicholas D embleton
AbstractPaediatricians are regularly faced with the question of when best to start
enteral feeds in preterm infants this is important as longer term out-
come may be compromised by sub-optimal nutrition in early life clinical
factors that may affect the decision to start and the risk and benefits
are discussed
Keywords breast milk feeding nutrition parenteral nutrition
Key points in the history
Alice is lsquonutritionally vulnerablersquo and whilst this may not be immediately apparent it will affect her long term outcome Her energy stores are extremely limited and consist primarily of pro-tein She has less than 5 fat and little energy associated with stored glycogen She is losing about 1 gkgd protein equivalent so she needs at least that and a minimum of 50ndash60 kcalkg of energy just to maintain the status quo let alone grow
Her weight is on the 25th centile Review of any antenatal his-tory may reveal whether fetal growth was normal Fetal growth retardation can occur with a weight greater than 10th centile The presence of antenatal absent or reversed end diastolic flow in the umbilical artery indicates poor gut blood flow This increases the risk of necrotizing enterocolitis (NEC) and might suggest a more cautious approach to starting feeds1
She has no important cardiovascular problems but if she were hypotensive gut blood flow may be low There is no umbilical
Nicholas D Embleton BSC (Hons) MBBS (Hons) MD FRCPCH is Consultant in
Neonatal Medicine at Newcastle Neonatal Service Royal Victoria
Infirmary Newcastle upon Tyne NE1 4LP UK
Should you start feeds at a day of age
alice was born following spontaneous labour at 30 weeksrsquo
gestation she weighed 1300 g and is now 18 h old she was
briefly ventilated and then extubated to continuous positive
airway pressure 12 h ago in 35 oxygen she has had caffeine
citrate but still has intermittent episodes of self-correcting
apnoea she was commenced on iv 10 dextrose but this was
replaced by a parenteral amino acid solution (referred to as
lsquotPnrsquo) along with intralipid at 0900 this morning serum glucose
is 11 mmoll and blood pressure is 42 systolic
PaeDiatrics anD cHilD HealtH 184 20
arterial catheter in situ but there is no good evidence that this should delay the decision to start feeds Her glucose is high but this is quite common in a baby like this Could this be a sign of sepsis Caffeine does not affect the incidence of NEC2 The great-est risk factor for NEC in this case is prematurity
What else might be found on examination
Up until 24 h ago she was swallowing large amounts of amniotic fluid What will have changed since then
General examination should confirm peripheral perfusion lsquogestaltrsquo view (does she look lsquowellrsquo) and cardiovascular status lsquoBowel soundsrsquo are not usually helpful
The most important variable likely to affect gut perfusion is the arterial duct Precordial lsquoheaversquo and a loud murmur are sug-gestive but it is possible to have a significant ductal shunt in a baby with a normal examination Cardiac ultrasound will con-firm this diagnosis It might be better to treat a large shunt first with indometacin and to delay starting feeds for a further 24 h
It is not possible to assess gut perfusion clinically but normal perfusion elsewhere (adequate urine output usually indicates adequate renal perfusion) would be reassuring Most preterm babies have a few abdominal lsquoloopsrsquo visible but a distended abdomen with many palpable loops suggests ileus This might be secondary to sepsis or poor gut blood flow Preterm babies do not pass much meconium in the first 24ndash48 h
Balance of risks between starting and withholding feeds
Alice requires 35ndash4 gkgd of protein and 120 kcalkgd to grow3 This will initially be provided parenterally Delaying feeds increases the risk of gut villous atrophy and prolongs the need for lsquototal parenteral nutrition (TPN)rsquo TPN requires intravenous access and so increases the risk of sepsis and when prolonged use is required combined with the lack of enteral feeding may result in hepatic impairment
Delaying feeds may allow a gut that has been chronically under-perfused to re-establish more normal perfusion although normal gut endocrine function digestive enzyme upregulation and motility require a source of intraluminal nutrients1 A recent study suggested benefit from delaying the introduction of feeds4 but methodologi-cal problems exist5 Although a Cochrane meta-analysis suggested no benefit only two studies were included6 A large UK-based trial is examining the effect of early or late feeding in preterm infants who were born growth retarded following identification of antena-tal absent or reversed end diastolic flow in the umbilical artery7
When starting feeds what volume should be used
There are no good data to guide this decision We start with 24 mlkg (1 mlkgh) and then increase by this amount each day Most babies achieve full enteral feeds (ge150 mlkgd) by a week of age Feeding guidelines improve the outcome8 Measure-ment or assessment of gastric aspirates is not consistently useful in predicting subsequent feeding intolerance or development of NEC Aspirate volumes equivalent to or sometimes greater than the amount given in the preceding 1ndash2 h are usually normal Most aspirates have a greenish colour Thick bloody or intensely bile-stained aspirates require detailed assessment
0 copy 2008 elsevier ltd all rights reserved
Personal Practice
What else affects decisions and outcome
Feeding success is affected by sepsis and NEC Scrupulous atten-tion should be paid to hand washing and intravenous access and blood sampling should be minimized There is no good evidence to support the routine use of pro-kinetic agents or H2 blockers
The most important clinical intervention affecting the occur-rence of NEC is the use of breast milk9 All efforts should be directed at persuading parents of the benefits and supporting the process Some clinicians delay starting feeds for a further 24 h whilst expressed breast milk becomes available Donor breast milk might be equally efficacious10
RefeRenceS
1 Dorling J Kempley s leaf a Feeding growth restricted preterm
infants with abnormal antenatal Doppler results Arch Dis Child Fetal
Neonatal Ed 2005 90 F359ndash363
2 schmidt B roberts rs Davis P et al caffeine therapy for apnea of
prematurity N Engl J Med 2006 354 2112ndash2121
PaeDiatrics anD cHilD HealtH 184 20
3 embleton nD Pang n cooke rJ Postnatal malnutrition and growth
retardation an inevitable consequence of current recommendations
in preterm infants Pediatrics 2001 107 270ndash273
4 Berseth cl Bisquera Ja Paje VU Prolonging small feeding volumes
early in life decreases the incidence of necrotizing enterocolitis in
very low birth weight infants Pediatrics 2003 111 529ndash534
5 Menon G Boyle eM embleton nD et al introduction of enteral
feeds in preterm infants Pediatrics 2004 114 327ndash328
6 Kennedy Ka tyson Je chamnanvanikij s early versus delayed
initiation of progressive enteral feedings for parenterally fed low
birth weight or preterm infants Cochrane Database Syst Rev 2000
cD001970
7 wwwnpeuoxacukadept
8 Patole sK de Klerk n impact of standardised feeding regimens on
incidence of neonatal necrotising enterocolitis a systematic review
and meta-analysis of observational studies Arch Dis Child Fetal
Neonatal Ed 2005 90 F147ndash151
9 lucas a cole tJ Breast milk and neonatal necrotising enterocolitis
Lancet 1990 336 1519ndash1523
10 Boyd ca Quigley Ma Brocklehurst P Donor breast milk versus
infant formula for preterm infants systematic review and meta-
analysis Arch Dis Child Fetal Neonatal Ed 2007 92 F169ndash175
1 copy 2008 elsevier ltd all rights reserved
self-assessment
Case 1A term male infant born to consanguineous parents is assessed at 24 h of age due to poor feeding profuse yellow watery diar-rhoea and irritability He weighed 32 kg at birth and delivery was uneventful There was no polyhydramnios He has been breastfed since birth On examination he is pale with a non-tender but distended abdomen and reduced bowel sounds His weight is 275 kg and he looks dehydrated Examination is otherwise normal
Initial investigations (normal values in parentheses) showed
sodium 149 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 65 mmollitre (25ndash75)
creatinine 147 μmollitre (40ndash110)
chloride 119 mmollitre (95ndash105)
haemoglobin 172 gdl (140ndash200)
White blood cell count 80 times 109litre (100ndash260)
Platelet count 302 times 109litre (150ndash400)
arterial blood gas
ph 720 (730ndash745)
PcO2 23 kPa (46ndash60)
Bicarbonate 68 mmollitre (220ndash260)
Base excess minus186 mmollitre (minus20 to +20)
lactate 59 mmollitre (06ndash24)
An abdominal X-ray shows distended bowel loops with no intramural thickening or pneumoperitoneum (Figure 1)
He was given nil by mouth and received intravenous fluids and antibiotics His dehydration improved but the metabolic acidosis and diarrhoea persisted despite receiving no enteral feeds and the commencement of total parenteral nutrition Blood and stool cultures were negative
1 Which of the following best describes these results Choose ONE answer ONLY from the followingA Hypernatraemia hyperchloraemic metabolic acidosis
with increased anion gapB Hypernatraemia hyperchloraemic metabolic acidosis
with normal anion gap
Manish Sadarangani BM BCh MA MRCPCH is Clinical Research Fellow
at the Department of Paediatrics University of Oxford Centre for
Clinical Vaccinology and Tropical Medicine Churchill Hospital
Oxford OX3 7LJ UK
Shabna Rajapaksa MB BChir MA MRCPCH is Specialist Registrar in
Paediatrics at the Paediatric Intensive Care Unit John Radcliffe
Hospital Oxford OX3 9DU UK
Nicholas Mann MD FRCP FRCPCH DCH is Consultant Paediatrician at the
Department of Paediatrics Royal Berkshire Hospital Reading RG1
5AN UK
self-assessment
C Hypernatraemic dehydration and compensated metabolic acidosis
D Acute renal failureE Renal tubular acidosis
2 What is the likely diagnosis Choose ONE answer ONLY from the followingA Hirschsprung disease ndash long segmentB Cystic fibrosis with meconium ileusC Microvillus inclusion diseaseD Cowrsquos milk protein intoleranceE Lactose intolerance
3 What is the investigation of choice Choose ONE answer ONLY from the followingA Rectal biopsy with staining for acetylcholine receptorsB Immunoreactive trypsinC Gastrointestinal endoscopy and biopsyD Stool microscopy and cultureE Stool reducing substances
Case 2A 4-year-old boy presents with a 3 d history of jaundice and a florid rash He has had orange urine and there is no change in his stool colour His family originate from Kosovo and have lived in the UK for the last 8 years He has never left the UK There is no history of blood transfusion or sex-ual abuse The grandmother was recently diagnosed with hepatitis B
On examination he is well apyrexial and mildly jaundiced with cervical and axillary lymphadenopathy He has an exten-sive papular rash over the face extremities and trunk (Figure 2) There is 3 cm hepatomegaly with no splenomegaly or ascites Examination is otherwise normal
Figure 1 abdominal X-ray of baby
Paediatrics and child health 184 202 copy 2008 elsevier ltd all rights reserved
self-assessment
Initial investigations are as follows
haemoglobin 110 gdl (113ndash135)
White blood cell count 108 times 109litre (50ndash150)
Platelet count 278 times 109litre (150ndash400)
inr 10 (08ndash12)
aPt ratio 10 (08ndash13)
sodium 140 mmollitre (135ndash145)
Potassium 42 mmollitre (35ndash50)
Urea 56 mmollitre (25ndash75)
creatinine 65 μmollitre (45ndash120)
total bilirubin 66 μmollitre (0ndash15)
conjugated bilirubin 23 μmollitre (0ndash10)
alanine aminotransferase (alt) 2033 iUlitre (0ndash35)
alkaline phosphatase 987 iUlitre (71ndash234)
Gamma-glutamyl transferase (GGt) 870 iUlitre (0ndash51)
1 What is the name of this rash Choose ONE answer ONLY from the followingA Erythema multiformeB Erythema migransC GianottiminusCrosti syndromeD EczemaE Dermatitis herpetiformis
2 What is the most likely diagnosis Choose ONE Answer ONLY from the followingA Autoimmune hepatitisB Hepatitis BC Hepatitis DD Wilson diseaseE Alpha-1 antitrypsin deficiency
3 What is the best means of management Choose ONE answer ONLY from the followingA Isolation until the jaundice disappearsB ImmunosuppressionC Copper chelating agents and genetic counsellingD Patient and family education with consideration of
antiviral agentsE Liver transplantation
Case 3A 10-month-old boy presents with 3 weeks of vomiting and constipation ndash he is passing hard stools every 2ndash3 days He has fallen from the 9th to below the 04th centile in the last 6 weeks He passed meconium within the first 24 h of life On examina-tion he looks pale and there are some dysmorphic features ndash a short nose long philtrum and wide mouth He has normal heart sounds with a grade 3 ejection systolic murmur loudest at the upper right sternal edge Examination is otherwise normal
Initial investigations are as follows
haemoglobin 91 gdl (113ndash141)
total white blood cell count 124 times 109litre (60ndash170)
Platelet count 407 times 109litre (150ndash400)
sodium 144 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 78 mmollitre (25ndash75)
creatinine 78 μmollitre (45ndash120)
albumin 52 glitre (35ndash50)
corrected calcium 384 mmollitre (238ndash263)
Phosphate 167 mmollitre (099ndash157)
1 What is the most likely diagnosis Choose ONE answer ONLY from the followingA HyperparathyroidismB Acute leukaemiaC Williams syndromeD Hypervitaminosis DE Familial hypocalciuric hypercalcaemia
2 Which investigation would be most useful in establishing the diagnosis Choose ONE answer ONLY from the followingA Intact parathyroid hormone assayB Blood filmC Fluorescent in-situ hybridization for 7q1123 deletionD 25-hydroxyvitamin D assayE Urine calciumcreatinine ratio
3 Which of the following treatments would not be suitable for this patient Choose ONE answer ONLY from the followingA Low calcium dietB Normal saline infusionC FurosemideD CorticosteroidsE Bisphosphonates
Case 4A 10-week-old girl presents with a 2-day history of poor feed-ing Her mother has been concerned about weakness since birth She only has a flicker of movement in the arms none in the legs and has a weak cry She has been passing urine and opening her bowels normally She was born at full term by normal delivery and did not require any resuscitation at birth Normal fetal movements were felt antenatally and there was no polyhydramnios She is the first child of non- consanguineous parents and there is no significant family his-tory On examination she is alert and fixing and following appropriately She has a weak cry and a weak suck There is reduced central and peripheral tone with marked head lag
Figure 2 rash found on examination
Paediatrics and child health 184 203 copy 2008 elsevier ltd all rights reserved
self-assessment
Muscle power is grade 3 out of 5 in the arms and legs There is no muscle or tongue fasciculation and she has absent reflexes throughout The remainder of the examination is normal
Electromyogram shows irregular polyphasic motor unit potentials with marked instability consistent with a dener-vating and re-innervating process (Figure 3)
1 Which of the following additional investigations may be helpful Choose ONE answer ONLY from the followingA Nerve conduction studiesB Creatine kinase assayC Muscle biopsyD SMN1 gene analysisE All of the above
2 What is the most likely cause of this childrsquos symptoms Choose ONE answer ONLY from the followingA Congenital myotonic dystrophyB Duchenne muscular dystrophyC PraderminusWilli syndromeD Spinal muscular atrophyE Mitochondrial myopathy
3 What is the mode of inheritance of this disease Choose ONE answer ONLY from the followingA X-linked recessiveB Autosomal recessiveC Autosomal dominantD MitochondrialE Sporadic
Case 5A 13-year-old girl presents with a 3-week history of fever up to 40degC night sweats and headache She has a reduced appetite with some weight loss She has no other specific symptoms She was on holiday in China 7 months ago On examination she looks well and has a temperature of 387degC There is no lymphadenopathy and no rashes Examination is entirely normal
Results of investigations are as follows
haemoglobin 126 gdl (120ndash160)
total white blood cell count 132 times 109litre (43ndash108)
neutrophil count 115 times 109litre (25ndash75)
Platelet count 244 times 109litre (150ndash400)
Blood film neutrophilia with left shift
erythrocyte sedimentation rate 63 mmh (1ndash20)
c-reactive protein 219 mglitre (0ndash5)
Blood culture Streptococcus intermedius
from anaerobic bottle only
csf culture negative
Magnetic resonance imaging (MRI) of the brain shows acute frontal sinusitis with a large intracranial frontal extra-dural empyema (Figure 4)
1 Which of the following would be appropriate management Choose ONE answer ONLY from the followingA A 12-week course of intravenous antibioticsB Drainage of the frontal sinus followed by 2 weeks of
intravenous antibioticsC Drainage of the empyema followed by 2 weeks of
intravenous antibioticsD Drainage of the empyema and the frontal sinus
followed by 2 weeks of oral antibiotics
1151
1152
1153
1154
1155
1156
1157
1158
1159
1200
50ms 1mV
Figure 3 electromyogram recording from the patient Figure 4 Parasagittal section from mri scan of patient
Paediatrics and child health 184 204 copy 2008 elsevier ltd all rights reserved
self-assessment
E Drainage of the empyema and the frontal sinus followed by 8 weeks of intravenous antibiotics
2 Streptococcus intermedius is a potential pathogen in which of the following infections Choose ONE answer ONLY from the followingA Liver abscessB Urinary tract infectionC MeningitisD Thoracic empyemaE Pneumonia
3 Which of the following statements regarding lsquopyrexia of unknown originrsquo in children is false Choose ONE answer ONLY from the followingA Malignancy is the underlying pathology in 5ndash15 of
casesB An aetiology will be found in over 90 of casesC The most common cause is infectionD A rheumatological cause is found in 10ndash20 of casesE Familial Mediterranean fever can occur in children of
non-Mediterranean ethnicity
Answers
Case 11 AThe anion gap is a useful tool to differentiate the causes of a metabolic acidosis It is calculated by the equation
Anion gap = [Na K ] [Cl HCO ]3+ + minus minus+ minus +
It represents the effect of unmeasured anions on the plasma pH and is normally 10ndash18 mmollitre
2 CMicrovillus inclusion disease is a severe autosomal recessive enteropathy that is typically apparent within hours or days after birth It is the second most common cause of protracted diarrhoea in the newborn after infectious causes It is characterized by severe yellow watery diarrhoea and malabsorption due to hypoplasia andor atrophy of the villi of the small intestine secondary to an inherited defect in the brush border membrane This results in severe dehydration malnutrition and metabolic acidosis due to bicarbonate loss from the gut
3 CDiagnosis of microvillus inclusion disease is made on small bowel biopsy Electron microscopy findings are of intracellular brush border inclusions and densely packed apical cytoplasmic vesicular bodies indicating microvillous atrophy There is no cure Treatment is supportive with total parenteral nutrition and consideration of small bowel transplantation
Further reAding
Goulet O ruemmele f causes and management of intestinal failure
in children Gastroenterology 2006 130(suppl 1) s16ndash28
rhoads Jm Vogler rc lacey sr et al microvillus inclusion disease
In vitro jejunal electrolyte transport Gastroenterology 1991
100 811ndash817
Case 21 CGianottindashCrosti syndrome is a distinct self-limiting rash commonly associated with viral infections in children between 2 and 6 years of age It presents as multiple pink to redminusbrown papules or papulovesicles which may be pruritic and can become confluent Gianotti and Crosti initially described the exanthema as associated with hepatitis B virus and they termed it papular acrodermatitis of childhood It can occur in several viral diseases eg hepatitis A B and C coxsackie viruses and cytomegalovirus
2 BHepatitis is a syndrome characterized by inflammation or injury of liver cells which may develop into cell necrosis and subsequently fibrosis andor cirrhosis Biochemically there are raised liver enzymes The degree of transaminase elevation does not correlate with the severity of the disease process Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of viral hepatitis
3 DHepatitis B infection is transmitted via blood sexually or vertically Infection may be acute or chronic Diagnostic markers are the presence of surface antigen (HBsAg) and HBV DNA The presence of e antigen (HBeAg) indicates high infectivity Infected newborns have a 95 risk of becoming carriers this risk decreases with infection acquired later in childhood Approximately 15ndash25 of HBV carriers will die from cirrhosis or hepatocellular carcinoma Extrahepatic findings are more common in older children and include membranous glomerulonephritis and GianottiminusCrosti syndrome Fulminant hepatic failure occurs in severe cases resulting in persistent jaundice encephalopathy and coagulopathy Management includes counselling family members monitoring for ongoing liver disease and consideration of antiviral therapy
Further reAding
Brandt O abeck d Gianotti r Burgdorf W Gianotti crosti
syndrome J Am Acad Dermatol 2006 54 136ndash145
slowik mK Jhaveri r hepatitis B and c viruses in infants and
young children Semin Pediatr Infect Dis 2005 16 296ndash305
Case 31 CHypercalcaemia is uncommon in infancy The most common symptoms in this age group are irritability vomiting and constipation It may be a manifestation of Williams syndrome vitamin D or calcium excess as well as disorders associated with reduced bone formation such as hypophosphatasia or increased bone resorption such as malignancy Occasionally
Paediatrics and child health 184 205 copy 2008 elsevier ltd all rights reserved
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-
SympoSium neonatology
Dry the babyRemove any wet towels and cover
Start the clock or note the time
Give 5 inflation breathsLook for a response
If no increase in heart rate look for chest movement
Re-check head positionApply Jaw thrust
Repeat inflation breathsLook for a response
If no increase in heart rate look for chest movement
Try alternative airway opening manoeuvresRepeat inflation breaths
Look for a response
If no increase in heart rate look for chest movement
If the heart rate is not detectable or slow (lt60)Start compressions
3 compressions to each breath
Reassess heart rate every 30 secondsConsider venous access and drugs
Assess colour tone breathing and heart rate
Open the airway
If not breathing
If still not breathing
If no response
If still no response
When the chest is moving
If meconium present
Baby breathing wellDo not suction the airway
Baby floppy and not breathing wellConsider inspection and suction before
inflation breaths
Head in neutral position
Inflation breathsUse a well-fitting face mask
connedted to a
pressure-limited gas supply
Each breath 2ndash3 seconds
duration at 30 cm H2O for a
term baby
Get help from a second personto support the airway andor
inspect the oropharynx under
direct vision and consider
suction andor insert an
oropharyngeal airway
Chest compressionsCompvent ratio 31
Rate 120 events per minute
Ensure the chest moves with each ventilation breath
If breathingReassess heart rate and monitor baby
If heart rate is satisfactory but increasingContinue ventilation breaths at about 30 per
minute until baby is breathing adequately
If heart rate is satisfactory but increasingContinue ventilation breaths at about 30 per
minute until baby is breathing adequately
If heart rate is increasingStop compressions
Continue ventilation breaths at about 30 per
minute until baby is breathing adequately
If the chest is not movingRecheck head position and repeat inflation
breaths If competent consider intubation
If the chest is still not movingThe airway is the problem
Figure 1 newborn life support (Courtesy of the Resuscitation Council uK)
heater14 There is a small risk of hyperthermia so the temperature must be monitored carefully
An assessment is made of the babyrsquos colour tone respira-tions and heart rate127 The most important of these is heart rate and a stethoscope is more reliable than cord pulsation15 How-ever saturation monitors may offer a more reliable assessment of both heart rate and colour16 but their interpretation requires a detailed knowledge of normal saturations at birth at differing gestations A baby who is apnoeic and floppy in the absence of neurological disease is unconscious and likely to be in terminal apnoea however this does not change the initial approach other
paeDiatRiCS anD CHilD HealtH 184 167
than the need to summon help early APGAR scores are never calculated to guide resuscitation
Airway
If a baby is in primary apnoea then with an open airway the first gasp will start to aerate the lungs and most babies will be able to lsquoresuscitatersquo themselves as shown in physiological stud-ies on animals Neutral positioning of the babyrsquos head chin lift jaw thrust oropharyngeal airways and endotracheal intubation may all be helpful in certain situations if performed correctly17
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Endotracheal intubationThe placement of an endotracheal tube has long been the gold standard of airway control and this remains true in the unconscious baby if it is correctly sized placed and fixed in a timely manner However experience is directly related to effec-tiveness in endotracheal intubation1819 and the success rate of less experienced clinicians such as a resident (STA1-3) or a fel-low (STA3-5) is lower varying between 33 and 68 Even senior neonatologists often take longer than guidelines recom-mend19 Experienced clinicians may judge correct endotracheal position visually or by an increase in heart rate with the first breaths but detection of exhaled carbon dioxide will give more rapid confirmation in larger babies12171920 and this can be par-ticularly useful for less experienced clinicians or those supervis-ing them However not all systems for the detection of exhaled carbon dioxide work in the smallest premature infants
Laryngeal masksLaryngeal masks may be effective for ventilating term newborn babies but there are few data for small premature infants There have been reports of dislodged laryngeal airways during paedi-atric arrests when chest compressions have been administered Although success of placement at first attempt by paediatri-cians is greater with a laryngeal mask than with an endotra-cheal tube21 the only and small randomized controlled trial in the delivery room favoured endotracheal intubation when per-formed by an anaesthetist22 Based mainly upon case reports the laryngeal mask can be recommended when positioning and mask ventilation and endotracheal intubation have failed to secure the airway but not as yet as a primary method of airway control
MeconiumIn 2000 Wisewell et al23 reported a large randomized controlled trial showing that tracheal intubation and suctioning of meco-nium-stained but vigorous babies at birth did not reduce the incidence or severity of meconium aspiration syndrome More recently another randomized trial has now shown that suction-ing on the perineum similarly offers no benefit24 Neither of these practices is recommended but intubation and suction of meconium from the trachea of non-vigorous babies born through meconium-stained liquor is still recommended
Breathing
In the apnoeic baby the first breaths establish the resting lung volume and aerate the fluid-filled alveoli This mechanical effect aided by surface tension within the alveoli causes the initial fall in pulmonary vascular resistance Experimentally this effect occurs even if the lungs are ventilated with nitrogen but is increased when air is used presumably due to the vasodilator effect of 21 oxygen The mechanical stretching of the lung also triggers the activation of cyclo-oxygenase beginning the production of prostacyclin Bradykinin is produced which has a further direct vasodilator effect and also possibly via prostacyclin Therefore adequate airway control and passive ventilation is vital not only because babies requiring resuscitation at birth have an almost uniformly respiratory aetiology but also in order to promote post-natal adaptation and reverse any maladaptation
paeDiatRiCS anD CHilD HealtH 184 16
In term babies peak ventilatory pressures of 20ndash30 cmH2O may be required but the minimal pressure needed to achieve an improvement in heart rate should be used or if there is no response chest wall movement Longer breaths at lower pressure may be more effective in displacing alveolar fluid and establish-ing the resting lung volume in lungs with sufficient surfactant and may improve initial oxygenation However premature new-borns are obviously physiologically and anatomically less pre-pared for delivery than infants at term Over-inflation has been implicated in histological lung damage in animal models and high tidal volumes appear to be equally damaging whether given before or immediately after administration of surfactant How-ever the same effect is not seen if these excessive tidal volumes are delivered 15 min after administration of surfactant2526 It is now thought that both excess end expiratory volume and inad-equate end-expiratory volume may cause lung damage2728 In premature infants it would therefore seem sensible to use lower pressures of 20ndash25 cmH2O12 delivered in a controlled way to prevent over-inflation and to apply positive end-expiratory pres-sure (PEEP) to prevent damage from under-inflation PEEP also improves both lung compliance and gas exchange2930 Without PEEP the airways collapse during the expiratory phase in animal models of newborn resuscitation
If animal data can be extrapolated it would also seem appro-priate to give surfactant as soon as possible to premature babies in order to ameliorate damage2526
The majority of newborn infants requiring resuscitation will re-establish regular respiration after administration of a few breaths which may be due to Headrsquos paradoxical reflex by which the inflation triggers an inspiratory effort
VentilationOnce the lungs are aerated if the newborn remains apnoeic ventilation should be continued at 30ndash60 breathsmin avoiding hyperventilation and using the minimum pressure possible to maintain a heart rate greater than 100 beatsmin
Face mask the majority of infants who require ventilation receive it via a face mask This may be attached to a bagvalve system with a spring lsquoblow offrsquo system or a lsquoT-piecersquo with a set flow and pressure It is important to realize that the bagvalve system is flow sensitive and that the harder the operator presses the greater the flow and the higher the delivered pressure In fact 60 cmH2O can be achieved with vigorous squeezing of a self-inflating bag Therefore it may be advantageous that most opera-tors are unlikely to be as effective as they suppose in creating a seal with the mask31 This is a skill that requires tuition and prac-tice31 In delivering a set pressure T-piece systems such as the Tom Thumbcopy or Neopuffcopy perform better than any bagminusvalve system but require a gas supply There is no evidence that lung compliance can be assessed using any bag system
Continuous airway pressure case series have suggested that early or delivery room use of continuous positive airway pres-sure (CPAP) in premature babies may reduce chronic lung dis-ease There have been two randomized trials of which one was a pilot study The data from the COIN trial do not show any advan-tage other than a reduction in intubation and surfactant use in the intervention group However an excess of pneumothorax
8 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
was also reported The Vermont Oxford Network and the SUP-PORT trials will provide further data but at present the delivery room use of CPAP cannot be widely recommended and should be limited to those units experienced in its use or taking part in research
Air or oxygen oxygen has been in widespread use for resuscita-tion at birth since the 1930s and even hyperbaric oxygen was seriously supported in the 1960s For many years there have been concerns about tissue damage from oxygen deprivation during and after resuscitation It became evident in the 1950s that unrestricted oxygen therapy could have serious conse-quences for future vision More recently concerns have been raised about potential adverse effects on respiratory physiology cerebral circulation and tissue damage from oxygen free radicals even during resuscitation A meta-analysis of four human studies demonstrated a reduction in mortality and no evidence of harm in infants resuscitated in air versus 100 oxygen3233 However there are several significant methodological concerns with these studies and the results should be interpreted with caution There is insufficient evidence to recommend any specific concentration of oxygen to be used for newborn resuscitation Monitoring the oxygen saturation of babies may be helpful but as yet there are no time-related normal target ranges and healthy term babies may take up to 10 min to achieve preductal oxygen saturation of greater than 95 and up to 60 min to achieve this postductally
There is therefore equipoise which would be open to an appropriate randomized controlled trial In the meantime the evidence only supports use of either 21 or 100 oxygen It is provoking to realize that if air had been in constant use since the 1930s there would be insufficient evidence for use of supple-mental oxygen
Circulation
Early resuscitation (temperature control airway breathing) provides oxygenated blood in the pulmonary arterioles which if returned to the heart causes the rate to increase34 If due to acidosis and hypoxia the circulation is ineffective then chest compressions may be needed They should be commenced when the heart rate remains below 60min despite effective airway and breathing management127 The best technique is using two hands to encircle the chest1 A ratio of three compressions to one breath is internationally accepted127 but has no evidence to support it Research has shown that neither compressions nor drugs will work in this situation without oxygenated blood so effective lung aeration and ventilation is essential A logical approach would be to fill the alveoli with air and to compress the chest until they are empty However training and teamwork require an agreed ratio which has therefore not changed since guidelines were first agreed internationally Success is assessed by an increase in heart rate which should therefore be assessed every 30 s Compressions stop when the spontaneous heart rate is greater than 60 beatsmin
In hypoxic newborn animal models successful resuscitation can restore cardiac output and blood pressure to levels above baseline within 5ndash10 min However it should be noted that there is a decline to 30 lower than basal levels within 2 h and that blood pressure is relatively spared suggesting an even greater
paeDiatRiCS anD CHilD HealtH 184 16
reduction in tissue perfusion This should be considered in the later care of any neonate who was hypoxic at birth
Drugs
Neonatal bradycardia at birth is almost always due to hypoxia plusmn acidosis and therefore drugs are rarely needed Adrenaline (epi-nephrine) is reported as being used in between 1 and 4 babies per 2000 births which is a large variation in practice Reported success is also variable and must be interpreted in light of this variation The use of drugs in extremely premature infants is con-troversial Some data suggested good outcomes for babies below 28 weeksrsquo gestation given adrenaline but these were flawed by high numbers of babies receiving resuscitative drugs some before the airway had been appropriately managed Audit data now suggest a poor outcome such that many clinicians would now council against the use of adrenaline and other drugs to resuscitate extremely premature newborn babies
Adrenaline (epinephrine)In 2003 a Cochrane review of randomized controlled trials involv-ing adrenaline use for resuscitation of neonates was unable to identify a single clinical trial35 Despite the lack of human neo-natal data animal models show the potential of adrenaline in asphyxial cardiac arrest and it is reasonable to use it when ade-quate ventilation and chest compressions have failed to increase the heart rate above 60 beatsmin Use 10ndash30 μgkg intrave-nously and preferably via an umbilical venous line The tracheal route cannot be recommended but if used it is likely that doses within this range will be ineffective and 100 μgkg might be tried However the safety of such doses has not been studied
BicarbonateThe use of bicarbonate has long been controversial but many of the concerns relate to the rapid correction of acidosis in neonates after resuscitation or the routine use of bicarbonate infusion nei-ther of which can be advocated There are no published human neonatal data to support its use although some exist from animal studies Animal data have also shown that the binding of adren-aline to receptors in the myocardium is significantly impaired by lactic acidosis and recent work on human lymphocyte beta-adrenergic receptors supports this view Whether this is also true of the more important alpha receptors is unknown In practice reversing intracardiac acidosis may improve myocardial function and assist in achieving a return of spontaneous circulation 1ndash2 mmolkg of bicarbonate may be given but this remains a contro-versial area
VolumeVolume expansion should only be given when it is suspected that the baby has suffered blood loss or the infant appears to be in shock (pale poor perfusion weak pulse) and has not responded adequately to other resuscitative measures If there is no history suggestive of blood loss shock is most likely to be due to myo-cardial dysfunction in which case fluids should be administered cautiously The most logical replacement fluid would be blood but in its absence isotonic crystalloid rather than albumin is the solution of choice given in 10 mlkg aliquots and observing the response Three randomized trials in neonates have shown
9 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
isotonic crystalloid to be as effective as albumin for the treat-ment of hypotension but none has examined either the relative or actual effectiveness in resuscitation A recent blinded randomized study comparing normal saline albumin or no volume expansion in a normovolaemic asphyxiated neonatal animal model showed that volume expansion was not beneficial and made a number of parameters worse36
NaloxoneNaloxone is not recommended as part of the initial resuscita-tion of newborns with respiratory depression Before it is given supporting ventilation should have restored the heart rate and colour The dose is 100 μgkg intravenously or intramuscularly Tracheal administration cannot be recommended Although administration of naloxone to neonates who have been exposed to maternal opioids during labour is a practice of long-standing it lacks the proper evidence of efficacy
Non-response to resuscitation
There are few more frightening situations professionally than applying the correct interventions in resuscitating or stabilizing a baby and getting no response Each stage must be adequately performed before moving onto the next and this requires regular reassessment When experienced help is needed at a newborn resuscitation it is usually the airway and ventilation that require correction If the heart rate does not increase this usually means that the lungs have not been successfully aerated In some cases however it may mean that the heart cannot respond as the cir-culation is inadequate In this situation the only way to check that the lungs have been successfully aerated is to see the chest move with ventilation or to obtain evidence of ventilation from a detector of exhaled carbon dioxide If you do not see chest movement after another five breaths the most likely cause is an obstructed airway either due to incorrect positioning or because the jaw has not been drawn forwards An oropharyngeal airway can be very helpful at this point especially in the term baby Only very occasionally is the airway blocked by mucus vernix blood or meconium but if the airway is guaranteed and there is no heart rate response or chest movement this should be sought by direct suction of the trachea even in the absence of any meconium staining of liquor Pneumothoraces can occur spontaneously after delivery but are rare at resuscitation carried out with pressure-limited devices Equally rare are diaphragmatic hernias that have not been diagnosed antenatally giving problems at resuscitation
If the chest is moving but the heart rate has not responded to resuscitation consider rare possibilities such as fetal blood loss pneumothorax or heart block (mothers with undiagnosed systemic lupus erythematosis delivered for fetal bradycardia) as possibilities With adequate ventilation there is no evidence of oxygen concentrations less than 100 being responsible for prolonged bradycardia or failure to respond although current practice would support increasing the delivered oxygen concen-tration if resuscitation had been commenced using air
Outcome
The prognosis for the full-term baby subjected to sudden acute asphyxia is usually good provided the episode does not last for
paeDiatRiCS anD CHilD HealtH 184 17
long Most babies resuscitated from primary apnoea have no sequelae secondary to the resuscitation Many babies who start to breathe again regularly within 20 min of the circulation being restored recover completely but it is rare for a baby who is still gasping after 30 min to recover
The prognosis for the preterm baby of less than about 34 weeksrsquo gestation subjected to severe acute anoxia is less predict-able This is because of the risk of secondary intraventricular haemorrhage or periventricular intracerebral haemorrhage andor infarction after even a relatively brief asphyxial episode espe-cially in the period immediately around birth
The effects of chronic hypoxia are also difficult to predict but a reasonably clear idea of the extent of the problem should be obtainable within 36ndash48 h of the original chronic asphyxial insult A mild short-lasting state of hyperexcitability usually car-ries a good prognosis even if there is seizure activity but more severe symptoms can be associated with permanent handicap This is seen especially in infants with encephalopathy requiring ventilation
REFERENCEs
1 Biarent D Bingham R Richmond S et al european Resuscitation
Council guidelines for Resuscitation 2005 Section 6 paediatric life
support Resuscitation 2005 67(suppl 1) S97ndashS133
2 international liaison Committee on Resuscitation part 7 neonatal
resuscitation Resuscitation 2005 67 293ndash303
3 Singh J Santosh S Wyllie J mellon a effects of a course in
neonatal resuscitation - evaluation of an educational intervention
on the standard of neonatal resuscitation Resuscitation 2006 68
385ndash389
4 palme-Kilander C methods of resuscitation in low-apgar-score
newborn infants - a national survey Acta Paediatr 1992 81
739ndash744
5 Kroll l twohey l Daubeney p et al Risk factors at delivery and
the need for skilled resuscitation Eur J Obstet Gynecol Reprod Biol
1994 44 175ndash177
6 Wyllie Jp Resuscitation of the newborn The Foundation Years
2007 3(4) 153ndash157
7 Richmond S ed newborn life Support Resuscitation at Birth
london Resuscitation Council 2006
8 Ceriani Cernadas Jm Carroli g pelligrine l et al the effect of timing
of cord clamping on neonatal venous hematocrit values and clinical
outcome at term a randomized controlled trial Pediatrics 2006
117 e779ndashe786
9 mercer JS Vohr BR mcgrath mm padbury JF Wallach m oh W
Delayed cord clamping in very preterm infants reduces the incidence
of intraventricular hemorrhage and late-onset sepsis a randomized
controlled trial Pediatrics 2006 117 1235ndash1242
10 Dahm lS James lS newborn temperature and calculated heat loss
in the delivery room Pediatrics 1972 49 504ndash513
11 Stephenson J Du J tk o the effect of cooling on blood gas
tensions in newborn infants J Pediatr 1970 76 848ndash852
12 gandy gm adamsons Jr K Cunningham n Silverman Wa James lS
thermal environment and acid-base homeostasis in human infants
during the first few hours of life J Clin Invest 1964 43 751ndash758
13 gluck l Kulovich mV eidelman ai et al Biochemical development
of surface activity in mammalian lung pulmonary lecithin synthesis
0 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
in the human fetus and newborn and etiology of the respiratory
distress syndrome Pediatr Res 1972 6 81ndash99
14 Vohra S Roberts RS Zhang B Janes m Schmidt B Heat loss
prevention (Help) in the delivery room a randomised controlled
trial of polyethylene occlusive skin wrapping in very preterm infants
J Pediatr 2004 145 750ndash753
15 owen CJ Wyllie Jp Determination of heart rate in babies at birth
Resuscitation 2004 60 213ndash217
16 orsquoDonnell Cp Kamlin Co Davis pg Carlin JB morley CJ Clinical
assessment of infant colour at delivery Arch Dis Child Fetal
Neonatal Ed 2007 92 F465ndashF467
17 international liaison Committee on Resuscitation part 13 neonatal
Resuscitation guidelines Circulation 2005 112(suppl 24)
iV188ndashiV195
18 leone ta Rich W Finer nn neonatal intubation Success of
pediatric trainees J Pediatr 2005 146 638ndash641
19 orsquoDonnell Cp Kamlin Co Davis pg morley CJ endotracheal
intubation attempts during neonatal resuscitation success
rates duration and adverse effects Pediatrics 2006 117
e16ndash21
20 Repetto Je Donohue pa-CpK Baker SF Kelly l nogee lm use of
capnography in the delivery room for assessment of endotracheal
tube placement J Perinatol 2001 21 284ndash287
21 gandini D Brimacombe JR neonatal resuscitation with laryngeal
mask airway in normal and low birth weight infants Anesth Analg
1999 89 642ndash643
22 esmail n Saleh m ali a laryngeal mask airway versus endotracheal
intubation for apgar score improvement in neonatal resuscitation
Egypt J Anesthiol 2002 18 115ndash121
23 Wiswell te gannon Cm Jacob J et al Delivery room management
of the apparently vigorous meconium-stained neonate results of
the multicenter international collaborative trial Pediatrics 2000
105 1ndash7
24 Vain ne Szyld eg prudent lm Wisewell te aguilar am Vivas ni
oropharyngeal and nasopharyngeal suctioning of meconium-stained
neonates before delivery of their shoulders multicentre randomised
controlled trial Lancet 2004 364 597ndash602
25 Bjorklund lJ ingimarsson J Curstedt t larsson a Robertson B
Werner o lung recruitment at birth does not improve lung function
in immature lambs receiving surfactant Acta Anaes Scand 2001 45
986ndash993
26 Bjorklund lJ ingimarsson J Curstedt t et al manual ventilation
with a few large breaths at birth compromises the therapeutic effect
of subsequent surfactant replacement in immature lambs Pediatr
Res 1997 42 348ndash355
paeDiatRiCS anD CHilD HealtH 184 17
27 taskar V John J evander e Robertson B Jonson B Surfactant
dysfunction makes lungs vulnerable to repetitive collapse and re-
expansion Am J Respir Crit Care Med 1997 155 313ndash320
28 muscedere Jg mullen JB gan K Slutsky aS tidal ventilation at low
airway pressures can augment lung injury Am J Respir Crit Care Med
1994 149 1327ndash1334
29 nilsson R grossman g Robertson B Bronchiolar epithelial lesions
induced in the premature rabbit neonate by short periods of artificial
ventilation Acta Pathol Microbiol Scand 1980 88 359ndash367
30 probyn me Hooper SB Dargaville pa et al positive end expiratory
pressure during resuscitation of premature lambs rapidly improves
blood gases without adversely affecting arterial pressure Pediatr
Res 2004 56 198ndash204
31 Wood Fe morley CJ Dawson Ja et al improved techniques
reduce face mask leak during simulated neonatal resuscitation
study 2 Arch Dis Child Fetal Neonatal Ed in press doi101136
adc2007117788
32 tan a Schulz a orsquoDonnell CpF Davis pg air versus oxygen for
resuscitation of infants at birth Cochrane Database Syst Rev 2004
(3) CD002273
33 Davis pg tan a orsquoDonnell Cp Schulze a Resuscitation of newborn
infants with 100 oxygen or air a systematic review and meta-
analysis Lancet 2004 364 1329ndash1333
34 Dawes g Fetal and neonatal physiology Chicago year Book
publisher 1968 p 141ndash159
35 Ziino aJa Davies mW Davis pg epinephrine for the resuscitation
of apparently stillborn or extremely bradycardic newborn infants
Cochrane Database Syst Rev 2003 (2) CD003849
36 Wyckoff m garcia D margraf l perlman J laptook a Randomized
trial of volume infusion during resuscitation of asphyxiated neonatal
piglets Pediatr Res 2007 61 415ndash420
Practice points
bull Resuscitation at birth is different from that at all other times
of life
bull a standard approach can be applied to most newborn
resuscitation
bull guidelines are based on a rigorous evaluation of evidence
where possible
bull evidence is sparse but evolving
bull most preterm babies require stabilization rather than
resuscitation
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Acidndashbase physiology and blood gas interpretation in the neonateSusern tan
morag Campbell
Abstractacidndashbase balance describes the complex processes that work to main-
tain a stable extracellular pH for optimal cellular function the process
of balancing the production and neutralization of tissue acid provides a
great challenge for newborn infants who have significantly higher rates
of acid production than adults Factors which help maintain a stable
acidndashbase balance include buffers the respiratory system and renal sys-
tem Both intracellular and extracellular buffers resist changes in pH
the most important extracellular buffer system for maintaining stable
pH is the bicarbonate system in response to acidosis or alkalosis the
respiratory system balances the production of acid with the clearance
of Co2 by altering respiratory rate the kidneys provide a delayed but
sustained response to pH imbalance by excreting either acidic or alkaline
urine in response to systemic acidosis and alkalosis respectively in sick
premature infants these systems have a limited capacity completely to
control pH this review discusses the physiology of the three systems
which control acidndashbase balance patterns of clinical abnormalities in
acidndashbase status and their underlying causes are discussed We present
a systematic approach to blood gas analysis and interpretation in new-
born infants
Keywords acidosis alkalosis bicarbonate bloodndashgas analysis
metabolic pH
Introduction
Blood gas analysis is a routine procedure performed on newborn babies receiving respiratory support in the neonatal intensive care The combination of invasive and non-invasive assessment of ventilation and oxygenation enables clinicians appropriately to modify respiratory care according to each individual babyrsquos rapidly changing clinical status
Understanding the fundamentals of acidndashbase balance helps us to use blood gas analysis not only to assess respiratory sta-tus but also to provide information on metabolic status and the adequacy of tissue perfusion
Susern Tan MBBS MRCP is Clinical Fellow at the Neonatal Intensive Care
Unit 6th Floor North Wing St Thomasrsquo Hospital London SE1 7EH UK
Morag Campbell MBChB MRCP is Consultant Neonatologist at the
Neonatal Intensive Care Unit 6th Floor North Wing St Thomasrsquo
Hospital London SE1 7EH UK
paeDiatRiCS anD CHilD HealtH 184 17
What is understood by acid-base balance
Acidndashbase balance refers to the complex physiological processes used by the body to maintain a stable extracellular pH1 A serum pH within the range of 735ndash745 provides the ideal environment for cellular metabolism Maintaining a stable pH is critical as the metabolic activity of proteins is pH dependent and small changes in hydrogen ion (H+) concentration can potentially alter physio-logical function
Acids are substances that yield free H+ in solution while a base accepts H+ and in solution combines with an acid to neu-tralize it In the normal metabolic state H+ are continuously pro-duced and neutralized to maintain a steady pH balance12 The rate of H+ production is two to three times higher in neonates because of their rapid growth rates and increased acid production from protein turnover and bone mineralization The challenge of maintaining a stable pH through processing and neutralizing H+ is therefore greatest in newborn infants
Using exact values of H+ concentration to assess acidndashbase status is cumbersome and it is more commonly expressed as pH defined by the equation
pH = minuslog H+
Maintaining acidndashbase balance
The balance between production and excretion of acids in the body is controlled by buffer systems which have an immediate effect and by the respiratory and the renal systems
Buffer systemsBuffer solutions resist change in pH when acid or alkali is added due to their capacity to absorb or give up H+ The three main buffer systems in the body are the bicarbonate phosphate and protein systems1ndash3 The protein and phosphate buffer systems are intracellular and act as lsquosinksrsquo for extracellular H+ which are exchanged with intracellular potassium (K+) and sodium ions (Na+) In an acute metabolic acidosis hyperkalaemia may develop due to this H+ exchange4
The bicarbonate buffer system is extracellular and consists of a mixture of carbonic acid (H2CO3) and sodium bicarbon-ate (NaHCO3) This buffer system helps maintain a stable pH by soaking up excess H+ with HCO3
minus which in solution forms carbonic acid (H2CO3) Carbonic acid is a weak acid and readily dissociates to give CO2 which is transported in dissolved form to the lungs for excretion
H+ + HCO3minus harr H2CO3 harr H2O + CO2
The bicarbonate system therefore completes the neutraliza-tion of excess H+ and a stable plasma pH is maintained The relationships between pH HCO3
minus and CO2 in this system are described by the HendersonndashHasselbalch equation15
pH = 61 + log HCO3minus003 times CO2
where 61 is the log of the dissociation coefficient of carbonic acid and 003 the solubility of CO2 in plasma Buffers are most potent when there are equal amounts of H+ and HCO3
minus in solution The
2 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
bicarbonate system is not a potent buffer however as HCO3minus
and CO2 are readily altered by the body this system plays a very powerful role in pH homeostasis15
Respiratory regulationThe respiratory system adapts within minutes to hours as part of the acute response to acidosis This system modifies pH by balancing production of H+ with ventilatory clearance of CO2
H+ directly stimulates chemoreceptors in the respiratory cen-tre of the brainstem producing an increase in respiratory rate26 The response to respiratory acidosis is very rapid as CO2 easily diffuses across the bloodndashbrain barrier however in metabolic acidosis compensation is delayed until plasma bicarbonate fully equilibrates with cerebrospinal fluid (CSF) bicarbonate There is an inverse relationship between alveolar ventilation and partial pressure of dissolved carbon dioxide (PaCO2) a reduction in alveolar ventilation raises PaCO2 and decreases pH Changes in pH therefore affect alveolar ventilation and conversely changes in alveolar ventilation cause significant changes in pH
Renal regulationThe kidneys provide a delayed but sustained response to acidndashbase imbalances by excreting either acidic or alkaline urine In full-term and preterm babies the capacity for acid excretion and bicarbonate reabsorption is reduced as glomerular filtration rates are low and tubular function immature7 Renal function matures with gestation postnatal age and glucocorticoid and thyroid hormones78 Due to their limited capacity to preserve HCO3
minus newborn infants have lower serum bicarbonate levels and are predisposed to acidosis7
Bicarbonate is not effectively reabsorbed due to its size and electrical charge Instead intraluminal HCO3
minus combines with secreted H+ in tubular luminal fluid to produce carbonic acid which dissociates to give H2O and CO2 This CO2 diffuses into tubular cells combines with intracellular H2O and forms carbonic acid which liberates HCO3
minus and H+ HCO3minus is then
recovered to the circulation by exchange for chloride ions (Clminus) through the basal cell membrane247
Renal acid secretion occurs at all sites except the loop of Henle Primary active transport accounts for 5 and secondary for the remaining 95 of total H+ excretion Secondary trans-port involves an exchange between luminal Na+ and intracel-lular H+ Both ions bind to a membrane transport protein The Na+ concentration gradient between the tubular lumen and cells enables Na+ drag into the cell which generates energy to fuel active H+ excretion into the tubular lumen1ndash47
Quantifying acidosis
Standard base excess is a calculated value derived from PaCO2 and pH It is expressed as the mmollitre of base above or below normal buffer bases required to correct the pH to 74 at a PaCO2 of 40 mmHg A negative base excess or base deficit indicates an acidosis while a positive base excess indicates a relative alkalosis15
Anion gap is the measured difference between anions and cations in the blood
Anion gap = (Na+ + k+) minus (HCO3+Clminus)
paeDiatRiCS anD CHilD HealtH 184 17
Calculation of the anion gap enables clinicians better to define the underlying cause of a metabolic acidosis9 The common causes of an increased anion gap acidosis in neonates include lactic acidosis due to tissue hypoperfusion and hypoxia it may also be seen with certain inborn errors of metabolism and in uraemia910 The anion gap can help distinguish between the rela-tively benign non-anion gap hyperchloraemic acidosis seen in premature infants and a pathological lactic acidosis due to poor end-organ perfusion1011
Strong ion theory
Stewart described a complex acidndashbase model which proposed that H+ concentration results from the dissociation of water which is influenced by PaCO2 the strong ion difference and plasma weak acids12
Strong ions are ions that dissociate at normal body pH and include Na+ K+ and Clminus Weak acids in plasma which contrib-ute include albumin inorganic phosphate and plasma proteins their concentrations do not change with pH and are therefore a constant The effect of these factors and other unmeasured tissue ions on acidndashbase status can be quantified by the calculation of the strong ion gap (SIG)112 In the neonatal unit it is perhaps more important that we consider how principles of this model may relate to acidndashbase status rather than fully to quantify the SIG Theoretically low albumin and phosphate levels which fre-quently occur in premature infants by reducing the concentra-tion of weak acids can produce a relative alkalosis while high phosphate levels in renal failure may contribute to acidosis
Tissue oxygenation
Oxygenation is closely linked to acidndashbase status as optimal cel-lular function requires oxygen to fuel aerobic metabolism and produce energy In hypoxic conditions anaerobic metabolism predominates which is energy inefficient and results in a lactic acidosis1011
Tissue oxygen availability is related to regional blood flow haemoglobin level and haemoglobin oxygen affinity Arterial blood gases measure the partial pressure of dissolved oxygen (PaO2) which represents a small component of total oxygen con-tent the majority being transported bound to haemoglobin The relationship between percentage haemoglobin saturation (SaO2) and PaO2 is described by the sigmoidal oxyhaemoglobin disso-ciation curve which enables us to relate the two measures to each other235 The affinity of haemoglobin for oxygen is altered by local tissue factors Increases in temperature H+ PaCO2 and 23-diphosphoglycerate (DPG) levels shift the oxyhaemoglobin dissociation curve to the right reducing affinity for oxygen Decreases in temperature H+ PaCO2 and 23-DPG levels shift the curve to the left increasing oxygen affinity1ndash35 In the body haemoglobin oxygen affinity continuously changes increasing in the lungs to enable efficient oxygen uptake and decreasing at tissue level to provide efficient oxygen delivery to metabolically active tissues
Avoiding both hypoxia and hyperoxia is important in the neo-natal unit as deleterious effects of hypoxia are seen in infants with pulmonary hypertension1314 while hyperoxia is associated with an increased incidence of retinopathy of prematurity1516
3 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Clinical acidndashbase imbalances
Clinical acidndashbase imbalances can be respiratory metabolic or a mixture of both These abnormalities may be corrected by the acidndashbase regulatory mechanisms in the body in an attempt to maintain normal pH (Figure 1)
Respiratory acidosisThis occurs when any disorder leads to decreased alveolar ventilation Common causes of respiratory acidosis are listed in Table 1 Reduced respiratory clearance of CO2 means more dissolved CO2 accumulates in the plasma leading to increased production of carbonic acid and H+ Through chemoreceptor stimulation respiratory acidosis rapidly alters ventilation in an attempt to reduce CO226 Chemoreceptor mediated ventila-tory increases may only partly adjust in premature infants with underlying lung disease In babies with a sustained respiratory acidosis eg in chronic lung disease then metabolic compen-sation occurs through increased renal excretion of H+ and reabsorption of HCO3
minus slowly restoring pH to around 80 of normal47
paeDiatRiCS anD CHilD HealtH 184 17
The management of PaCO2 levels in infants receiving mechan-ical ventilation has important clinical implications Premature babies have impaired cerebral autoregulation17 and adverse neurological sequelae are reported in association with high PaCO2 levels18ndash20 Ventilation strategies which advocate lsquoper-missive hypercarbiarsquo have been developed to minimize airways damage from mechanical ventilation21 Published data suggest pulmonary benefits however the safe level of PaCO2 remains to be defined in premature infants2021
Respiratory alkalosisThis occurs when more CO2 is excreted than is produced by the body Pathological conditions leading to respiratory alkalosis are rare Hyperventilation in the neonatal setting is often iatrogenic or may be due to disorders in brainstem control of breathing including hypoxicndashischaemic encephalopathy or primary central nervous system abnormalities (see Table 1)
If respiratory alkalosis is sustained it may be compensated for by reduced reabsorption of filtered bicarbonate Reported adverse associations of low PaCO2 include periventricular leuco-malacia and intraventricular haemorrhage1922
K+
H+
Overventilation
CO2 + H2O harr H2CO3 harr H+ + HCO3ndash
Bicarbonate Buffer
Intracellular Buffer
uarr H+ excretionuarr HCO3
ndash absorption
uarr buffered H+
(NH4+ H2PO4
ndash)uarr ventilation rate
RespiratoryAcidosis
MetabolicAcidosis
darr CO2and uarr pH
RespiratoryAlkalosis
MetabolicAlkalosis
darr H+ anduarr pH
darr ventilation rate
uarrCO2
and darr pH
darr H+ excretiondarr HCO3
ndash absorption
uarrH+ and
darr pH
Brain
Brain
Intracellular Buffer
H+
K+
Sepsis
HypoxiaRDS
Metabolismand growth
Diuretics
Airwayobstruction
Neuromuscularproblems
IEM
Gastric losses
+ +
ndash -
Renal BufferRespiratory Buffer
Figure 1 mechanisms for regulation of extracellular pH iem inborn errors of metabolism RDS respiratory distress syndrome
4 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Common causes of acidndashbase imbalances
pH PCO2 H2CO3 Base excess Common neonatal causes
Respiratory acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
uarr normal normal bull upper airway obstruction choanal atresia
pierre-Robin sequence
bull lung abnormalities respiratory distress
syndrome transient tachypneoa of
newborn pneumonia meconium aspiration
syndrome pulmonary hypoplasia
congenital pulmonary malformations
bull Central hypoventilation hypoxic-ischaemic
encephalopathy intracranial haemorrhage
bull neuromuscular insufficiency congenital
myopathies congenital neuropathies
bull iatrogenic inadequate ventilatory settings
Compensated lower limit
of normal
uarr uarr gt+3
metabolic acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
normal darr ltminus3 increased anion gap
bull lactic acidosis sepsis hypoperfusion
shock necrotizing enterocolitis
bull inorganic acidosis inborn errors of
metabolism renal failure
normal anion gap
bull increased gastrointestinal H2Co3 losses
ileostomy diarrhoea
bull Renal tubular acidoses
Compensated lower limit
of normal
darr darr ltminus3
Respiratory alkalosis Uncompensated gt 745 darr normal normal bull iatrogenic excessive ventilatory settings
bull Compensatory hyperventilation hypoxic-
ischaemic encephalopathy
Compensated higher limit
of normal
darr darr ltminus3
metabolic alkalosis Uncompensated gt 745 normal uarr gt+3 bull gastric losses vomiting non-replacement
of excessive nasogastric aspirates
bull thiazide and loop diuretics
bull Hypokalaemia
Compensated higher limit
of normal
uarr uarr gt+3
Table 1
Metabolic acidosisThis frequently affects infants in the neonatal unit and has many causes1011 (see Table 1) There may be overproduction of tissue acid impaired acid clearance gastrointestinal loss of bicarbonate or an exogenous increased acid load eg chloride total paren-teral nutrition (TPN) or albumin1ndash323
Calculation of the anion gap to distinguish an increased anion gap acidosis from a non-anion gap acidosis is important both for treatment and prognosis1011 Acidosis stimulates respiratory compensation but this is limited in unstable infants Similarly renal compensation with improved HCO3
minus conservation is con-strained by tubular immaturity Treatment of the acidosis should be directed at the underlying cause eg hypoxia hypotension or excess Clminus rather than by administration of base
Metabolic alkalosisThis is unusual in neonates and is most frequently seen in infants with chronic lung disease or heart failure who are receiving diuretics Diuretics cause alkalosis by increasing renal fluid and Na+ losses An active process to reabsorb Na+ occurs in tubule cells which through enhanced H+ secretion and HCO3
minus reab-sorption produce alkalosis27
paeDiatRiCS anD CHilD HealtH 184 17
Metabolic alkalosis may also occur with excessive loss of gas-tric contents eg protracted vomiting or inadequate replacement of nasogastric aspirates (see Table 1)
Interpreting blood gases
Blood gas measurements can provide important diagnostic and prognostic information and a systematic approach to blood gas analysis is described in Table 2 The clinical management of infants with abnormal gases requires a good understanding of acidndashbase physiology and tissue oxygenation and an apprecia-tion of factors which may affect the reliability of samples
Arterial blood sampling is the gold standard however indwelling arterial catheters and arterial stab samples are usually restricted to infants who are critically ill or those who require sig-nificant ongoing intervention Gases are most frequently measured in capillary or venous samples which correlate well with arterial samples for PaCO2 pH and base excess in babies and children receiving intensive care These correlations however are not valid in infants with peripheral vasoconstriction and hypotension2324
Non-invasive monitoring techniques may enable us to reduce the frequency of blood gas sampling Transcutaneous monitoring
5 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
A systematic approach to blood gas analysis
1 Collect the relevant information
bull type of gas ndash capillary or arterial
bull Current respiratory support ndash document level
bull transcutaneous Co2 and Sao2 levels
bull Clarify no significant clinical events before sampling
2 pH accept a range between 730 and 745 in newborn
babies this is lower than in older children is there an
alkalosis (pH gt 745) or an acidosis (lt 730)
3 Co2 aim for a range between 45 and 65 kpa a paCo2 level
more than 65 kpa suggests inadequate alveolar ventilation
while less than 45 kpa suggests hyperventilation Correlate
values with non-invasive measures
4 o2 Can only be assessed from arterial gases aim for pao2
between 60 and 80 kpa Correlate results with pulse
oximetry levels
5 HCo3 and base excess normal HCo3 level is between 20 and
24 mmollitre and bases excess +3 to minus3
6 anion gap look at the anion gap and lactate to help identify
the cause of an acidosis normal lactate levels should be less
than 2 mmollitre
7 Respiratory or metabolic compensation look at the pH and
assess whether it is appropriate for the Co2 level or is there
evidence of compensation
8 interpret use both the clinical history and blood gas
findings to help you identify the primary problem aim your
management at treating the underlying cause
9 Reassess if clinical management changes have been made
repeat the blood gas after an appropriate time interval to
ensure improvement
Table 2
provides a highly accurate and reliable method for measuring PaCO2 through the skin it can however be technically difficult may cause tissue damage and is of limited reliability when peripheral perfusion is reduced25 Continuous end-tidal CO2 measurements correlate well with arterial CO2 values in patients with normal ventilation and perfusion however in babies with lung disease alveolar collapse small tidal volumes and rapid respiratory rates can make these measurements unreliable26 Despite its limitations transcutaneous monitoring provides the best method for CO2 trend monitoring in the neonatal intensive care unit (NICU)25
Oxygen saturation levels can be continuously measured non-invasively using pulse oximetry While oximetry is easy to perform and accurate on occasion SaO2 levels obtained may be unreliable when tissue perfusion is poor or with movement artefact SaO2 monitoring is highly sensitive at detecting hypoxia but is limited in detecting hyperoxia as at levels more than 90 small changes in SaO2 may result in unacceptably large increases in PaO227 It is therefore essential that SaO2 alarm limits are set for all neonates receiving respiratory support to detect hypoxia and prevent hyperoxia1627
Continuous non-invasive monitoring provides invaluable information when managing complex infants in the NICU but it does not replace the need for regular blood gas analysis
paeDiatRiCS anD CHilD HealtH 184 17
ReFeRenCeS
1 Kellum Ja Determinants of blood pH in health and disease
Crit Care 2000 4 6ndash14
2 Quigley R Baum m neonatal acid base balance and disturbances
Semin Perinatol 2004 28 97ndash102
3 Brouillette Rt Waxman DH evaluation of the newbornrsquos blood gas
status Clin Chem 1997 43 215ndash221
4 Chan JC acid-base disorders and the kidney Adv Pediatr 1983 30
401ndash471
5 Siggaard-andersen o the pH-log pCo2 blood acidndashbase nomogram
revised Scand J Lab Invest 1962 14 598ndash604
6 Saetta m mortola Jp interaction of hypoxic and hypercapnic stimuli
on breathing pattern in the newborn rat J Appl Physiol 1987 62
506ndash512
7 Baum m Quigley R postnatal renal development in Seldin DW
giebisch g eds the kidney physiology and pathophysiology new
york lippincott Williams and Wilkins 2000 p 703ndash726
8 ortiz la Quan a Weinberg a et al effect of prenatal
dexamethasone on rat renal development Kidney Int 2001 59
1663ndash1669
9 gabow pa Kaehny WD Fennessey pV goodman Si gross pa
Schrier RW Diagnostic importance of an increased serum anion gap
N Engl J Med 1980 303 854ndash858
10 lorenz Jm Kleinman li markarian K oliver m Fernandez J Serum
anion gap in the differential diagnosis of metabolic acidosis in
critically ill newborns J Pediatr 1999 135 751ndash755
11 Deshpande Sa platt mp association between blood lactate and
acid-base status and mortality in ventilated babies Arch Dis Child
1997 76 F15ndash20
12 Stewart pa modern quantitative acid-base chemistry Can J Physiol
Pharmacol 1983 61 1444ndash1461
13 Dakshinamurti S pathophysiologic mechanisms of persistent
pulmonary hypertension of the newborn Pediatr Pulmonol 2005
39 492ndash503
14 mourani pm ivy DD gao D abman SH pulmonary vascular
effects of inhaled nitric oxide and oxygen tension in
bronchopulmonary dysplasia Am J Respir Crit Care Med 2004
170 1006ndash1013
15 Deulofeut R Critz a adams-Chapman i Sola a avoiding hyperoxia
in infants le 1250 g is associated with improved short- and long-
term outcomes J Perinatol 2006 26 700ndash705
16 Chow lC Wright KW Sola a Can changes in clinical practice
decrease the incidence of severe retinopathy of prematurity in very
low birth weight infants Pediatrics 2003 111 339ndash345
17 Boylan gB young K panerai RB Rennie Jm evans DH Dynamic
cerebral autoregulation in sick newborn infants Pediatr Res 2000
48 12ndash17
18 Kaiser JR gauss CH pont mm Williams DK Hypercapnia during
the first 3 days of life is associated with severe intraventricular
hemorrhage in very low birth weight infants J Perinatol 2006 26
279ndash285
19 Fabres J Carlo Wa phillips V Howard g ambalavanan n Both
extremes of arterial carbon dioxide pressure and the magnitude of
fluctuations in arterial carbon dioxide pressure are associated with
severe intraventricular hemorrhage in preterm infants Pediatrics
2007 119 299ndash305
20 thome uH Carroll W Wu tJ et al outcome of extremely preterm
infants randomized at birth to different paCo2 targets during the
first seven days of life Biol Neonate 2006 90 218ndash225
6 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
21 Carlo Wa Stark aR Wright ll et al minimal ventilation to prevent
bronchopulmonary dysplasia in extremely-low-birth-weight infants
J Pediatr 2002 141 370ndash374
22 okumura a Hayakawa F Kato t et al Hypocarbia in preterm
infants with periventricular leukomalacia the relation between
hypocarbia and mechanical ventilation Pediatrics 2001 107
469ndash475
23 peters o Ryan S matthew l Cheng K lunn J Randomised
controlled trial of acetate in preterm neonates receiving parenteral
nutrition Arch Dis Child 1997 77 F12ndash15
24 yildizda D yapiciolu H yilmaz Hl Sertdemir y Correlation of
simultaneously obtained capillary venous and arterial blood gases
of patients in a paediatric intensive care unit Arch Dis Child 2004
89 176ndash180
25 aliwalas ll noble l nesbitt K et al agreement of carbon
dioxide levels measured by arterial transcutaneous and end tidal
methods in preterm infants 28 weeks gestation J Perinatol 2005
25 26ndash29
26 Hagerty JJ Kleinman me Zurakowski D et al accuracy of a new
low-flow sidestream capnography technology in newborns a pilot
study J Perinatol 2002 22 219ndash225
paeDiatRiCS anD CHilD HealtH 184 17
27 poets CF Wilken m Seidenberg J Southall Dp von der Hardt H
Reliability of a pulse oximeter in the detection of hyperoxemia
J Pediatr 1993 122 87ndash90
Practice points
bull a stable extracellular pH is important for optimal cellular
functioning
bull abnormalities in acidndashbase balance are regulated by buffer
systems and the respiratory and renal tract
bull maintaining a stable pH is challenging for newborn babies
due to their high rates of acid production and immature
regulatory mechanisms
bull arterial or capillary blood gases provide an effective way to
monitor acidndashbase balance in newborns
bull Blood gases should be analysed in a structured manner
assessing pH and then respiratory and metabolic components
bull the treatment of acidndashbase abnormalities should be directed
at the underlying problem not merely at correcting pH
7 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Recognition and management of neonatal seizuresmalcolm levene
AbstractSeizures are the most common major manifestation of central nervous
system dysfunction in the newborn there are many causes but perina-
tal asphyxia and haemorrhagicinfarction lesions account for about 75
there is now considerable evidence that frequent but short seizures in
the neonate affect subsequent neurodevelopmental outcome Studies
using eeg or modified continuous tracing of eeg activity (aeeg or CFm)
have shown that there is often electroconvulsive dissociation this re-
fers to poor correlation between electrical seizures and clinical seizures
Commonly used anticonvulsants appear to increase electroconvulsive
dissociation effective management of neonatal seizures has proved very
disappointing and less than 50 of seizures are abolished by first-line
anticonvulsant medication (phenobarbitone or phenytoin) Drugs such
as midazolam and lidocaine may further reduce seizures but require
more evaluation the challenge is to assess new and more effective anti-
convulsants which are themselves associated with little neurotoxicity
Keywords antiepileptic drugs eeg neonatal seizures neurodegeneration
Convulsions are the most common major neurological sign seen in newborn infants and their incidence estimated from large population studies is 26 per 1000 live births1 Premature infants are over four times more likely to have convulsions than full-term infants12 Neonatal status epilepticus (continuous seizure activity lasting 30 min or more) diagnosed clinically is rare and accounts for only 5 of infants with seizures1 although this is now recognized more frequently as the result of continuous EEG monitoring3
Neonatal convulsions are described as presenting in a num-ber of different ways and various seizure types can be seen in the same baby over a number of hours The frequencies of the various patterns of seizure activity are given in Table 1 In very premature babies and to a lesser extent in term infants minor movement abnormalities may be difficult to identify as subtle seizures These include lip smacking tongue thrusting mouth-ing pedalling type movements of the lower limbs or swimming movements of the arms Apnoea can be a common manifesta-tion of subtle seizures The signs can be protean and vary from baby to baby or even in the same baby Virtually any stereotypic
Malcolm Levene MD FMedSc FRCPCH FRCH is Professor and Head of
Department of Paediatrics and Child Health at University of Leeds Leeds
and Honorary Neonatologist at Leeds General Infirmary Leeds UK
paeDiatRiCS anD CHilD HealtH 184 178
movement may be a manifestation of a seizure disorder in the newborn
Aetiology
The more carefully the fitting baby is investigated the more likely it is that a cause for the seizures will be found A number of recent papers have described the aetiology of neonatal con-vulsions after extensive investigations14 Tekgul et al4 recently studied a consecutive group of full-term infants with evidence of neonatal convulsions (recognized both clinically and on EEG) and reported their outcome Table 2 summarizes these data as well as risk of moderate or severe disability for each causative factor Perinatal asphyxia is the commonest cause for convul-sions in term infants with haemorrhagic or ischaemic lesions also being common
Overall the prognosis for the group of term babies with con-vulsions was good 72 had a favourable outcome Where asphyxia (hypoxicndashischaemic insult) is the cause of neonatal convulsions the outcome is poor in 50 The prognosis for neonatal convulsions when they were due to arterial or cere-brovenous infarction or intracranial haemorrhage was generally good Individually inborn errors are a very rare cause of neo-natal convulsions but in view of the treatable nature of some of these it is essential that these be considered and investigated appropriately5
Patterns of seizure activity in the newborn
Movement pattern Frequency ()
Clonic 50
tonic 20
Subtle 10ndash35 depending on maturity
myoclonic 5
Table 1
Cause incidence and outcome of neonatal convulsions in term infants14
Aetiological factor Incidence () Poor outcome ()
asphyxia 38ndash40 50
Cerebral arteriovenous
infarction
20 0
intracranial haemorrhage 12ndash20 13
Congenital cerebral anomaly 5ndash10 100
Hypoglycaemiahypocalcaemia 3ndash19
infection 3ndash20
inborn error of metabolism 1
unknown cause 10ndash13 0
Refers to moderate and severe neurodevelopmental abnormalitynumbers too small to make meaningful predictions
Table 2
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Controversies in the clinical management of neonatal seizures
In recent years we have learnt much more about the neurobi-ology of seizures and their effect on the developing brain The neonatal brain is in a neurophysiologically hyperexcitable state compared to the more mature brain and therefore is more prone to seizure activity This is due largely to a relative excess of GABA neuroreceptors GABA receptors are usually inhibitory but in the immature brain they have a paradoxically excitatory effect This changes at about term in primates and with progressive develop-ment they adopt a neuroinhibitory role6
The propensity to seizures in the neonatal brain makes resolv-ing the balance of risks between continuing seizure activity on the one hand against potentially adverse effects of therapy on the other a very important equation Added to this is the problem of accurately diagnosing neonatal seizures and whether commonly used anticonvulsants are successful in controlling them
These conundrums can be posed as a series of challenging questions which are discussed below
Do neonatal convulsions cause brain injuryConvulsions are a sign of neurological compromise and may indi-cate significant underlying structural brain damage or biochemi-cal disturbance which may cause further brain damage in its own right There has been considerable debate about the scale of the disability that convulsions cause the immature brain over and above that due to the underlying cause Most of our knowledge comes from studies in rodents and these have provided some tentative answers to this question
Seizures in the mature brain lead to neuronal necrosis but studies in very young rat pups whose brain development is somewhat similar to full-term infants have shown that a series of five brief seizures on five successive days does not cause struc-tural neuronal damage but does produce morphological changes in hippocampal neurones and worryingly deficits in the rat learning and visual spatial memory function in adolescent and adult life7 A single prolonged neonatal convulsion in similarly immature rats does not produce any functional effects8 Others have shown that following priming of the neonatal rat brain by short seizures as described above a further insult comprising induction of status epilepticus in the same rats at an older age causes neuronal necrosis9 This has been referred to as the lsquotwo hit hypothesisrsquo10
A more specific question is does seizure activity in an already significantly compromised brain cause additional neuropathol-ogy Wirrell et al11 studied a series of immature rat pups with the induction of an hypoxicndashischaemic (asphyxial) insult fol-lowed by either chemically-induced fits or a control sham pro-cedure In the more severely asphyxiated animals the degree of brain damage was increased significantly in those that had the additional burden of induced seizures
In summary these studies show that the immature brain is more resistant to short frequent post-seizure damage than the mature brain but despite resulting in no loss of neuronal numbers the function of the brain is permanently affected in later life In the asphyxiated brain seizures appear to have an additional adverse effect on brain damage Furthermore the immature brain that has been lsquoprimedrsquo by early seizures is more
paeDiatRiCS anD CHilD HealtH 184 179
vulnerable to status epilepticus later in life It would appear from these data that frequent seizures in the human infant should be stopped and this begs the question as to whether currently used anticonvulsants effectively control neonatal seizures
Can we rely on clinical versus EEG diagnosis of neonatal convulsionsTraditionally the diagnosis of neonatal convulsions has been made by observation and description of the frequency of abnor-mal movements EEG has been technically difficult in the hostile electrical activity of a neonatal intensive care environment and considerable expertise is required for analysis of the trace It is usually not practical to undertake traditional EEG recordings at the time the baby shows abnormal movements More recently various technological developments have allowed more direct investigation of neuronal electrical activity by either video-EEG or compressed recording of the amplitude integrated EEG (aEEG or CFM)
Rennie et al3 at Kingrsquos College Hospital London have under-taken extensive evaluation of video-EEG and have found that this technique detects many convulsions not recognized by a single channel aEEG or CFM trace Of 19 infants with evidence of convulsions on EEG only four were recognized on CFM but this may have been due to the observersrsquo lack of experi-ence with this technique In other centres that have developed appropriate expertise aEEG or CFM has proved more sensitive to the detection of seizures Video-EEG studies have also shown that many movements interpreted by experienced clinicians to be seizures are not associated with abnormal cortical activity Conversely many electrical seizures are not associated with abnormal movements This is referred to as electroconvulsive dissociation
In summary clinical observation alone to detect the fitting baby is unreliable in that it may either over-detect seizure activ-ity which is not present on EEG or under-detect clinical seizures in infants with EEG-proven convulsions The decision as to which babies to treat with antiepileptic drugs therefore becomes somewhat arbitrary
Do anticonvulsants stop neonatal seizuresAlthough neonatal seizures are common there are few random-ized controlled trials assessing the benefits of antiepileptic drugs (AEDs) in the treatment of this condition Phenobarbitone is the most widely used first-line AED and in an Australasian study 95 of neonatologists and paediatric neurologists used this drug as first-line management12 The most commonly used loading dosage is 20 mgkg but regimens of up to 40 mgkg have been recommended (Table 3)13 Four trials have evaluated the effect of phenobarbitone in abolishing neonatal seizures Two of these studies used EEG to monitor response to the drug1415 and one compared phenobarbitone with phenytoin15 In the latter study seizures were completely controlled in only 43 of babies and in the group where phenytoin was the first drug used com-plete seizure control was achieved in 45 This study switched babies from their first AED to the other if complete control was not obtained on EEG monitoring after exposure to first-line therapy In babies who had been given phenobarbitone as first-line therapy seizure control was only achieved in 57 after phenytoin was added In those given phenytoin first complete
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Dosage regimens for first- second- and third-line anticonvulsants in the neonatal period
Loading dose Second loading dose if first
unsuccessfulMaintenance dose
phenobarbitone 20 mgkg by slow iv injection 10 mgkg iv 25ndash5 mgkg od
phenytoin 20 mgkg iv over 20 min not recommended
midazolam 150ndash200 μgkg iv infusion 1 μgkgmin iv infusion increasing to 5 μgkgmin
until favourable response
lidocaine 2 mgkg iv over 10 min 6 mgkgh for 6 h iv then 4 mgkgh for 12 h then
2 mgkgh for 12 h
lorazepam 005ndash01 mgkg by slow iv injection
Diazepam 03ndash04 mgkg iv over 3ndash5 min
lidocaine should not be used if the infant has previously been treated with phenytoin
Table 3
seizure control was achieved with the adding of phenobarbitone in 62
Boylan et al14 assessed the efficacy of phenobarbitone (20ndash40 mgkg iv over 20 min) in 14 babies monitored by video-EEG in only four was there complete abolition of seizures and in the other 10 electroconvulsive seizure activity increased whereas clinical evidence of seizures reduced This has been termed elec-troclinical dissociation and anticonvulsant drug use in the new-born appears to increase this feature They also showed that the babies least likely to respond to the first-line AED are those with the most abnormal background EEG
Two studies have evaluated the use of phenobarbitone in babies who had sustained significant asphyxial insult at birth Hall et al13 compared high-dose phenobarbitone (mean 39 mgkg) versus standard dose (27 mgkg) and reported fewer convul-sions and a significant reduction of severe disability or death in the high dose group (RR 030 CI 010ndash093) A recent study from India16 of babies with hypoxicndashischaemic encephalopathy ran-domized 25 babies to phenobarbitone (20 mgkg loading dose) and compared them with 20 control babies Only 2 of 25 (4) in the phenobarbitone group developed convulsions compared with 8 of 20 (40) in the control group (p = 001) Because of the specific enrolment criteria (asphyxial insult) neither of these studies is strictly comparable to the studies by Painter et al15 and Boylan et al14 whose intention was to assess the efficacy of first-line anticonvulsant therapy on convulsions of any cause diagnosed either clinically or by EEG
Other anticonvulsants used as second- and third-line drugs have been subject to few studies in the newborn Midazolam is administered as a bolus followed by continuous infusion A recent study17 has shown that in 10 of 13 neonates given intravenous midazolam for status epilepticus control of electri-cal seizures was achieved within the first hour of treatment having been previously shown to be refractory to phenobarbi-tone treatment Some of these babies required a second bolus infusion of midazolam to obtain control of all electrographic seizures
In some parts of Europe lidocaine is used as a third-line anti-convulsant Malingre et al18 evaluated 20 infants refractory to
paeDiatRiCS anD CHilD HealtH 184 180
both phenobarbitone and midazolam and who were then given lidocaine by continuous infusion Lidocaine was effective in abolishing electroconvulsive seizures diagnosed by aEEG in 76 of the treatment courses studied No babies developed cardiac arrhythmias a previously reported complication of lidocaine in older patients As a result of pharmacokinetic studies the dosage regimen has been modified (see Table 3)
In summary phenobarbitone is effective in seizure control in less than 50 of babies and even when combined with phe-nytoin the efficacy of these drugs together remains poor More worrying is the observation that phenobarbitone tends to reduce clinically evident seizures thereby giving the clinician a false sense of security whilst having little or no effect on the num-bers of electroconvulsive disorders This has been summarized appropriately as lsquoafter all these years we still love what doesnrsquot workrsquo19 Both midazolam and lidocaine infusions appear to be effective in abolishing severe seizures in some infants resistant to phenobarbitone Lidocaine should not be given to babies previ-ously exposed to phenytoin for fear of a synergistic adverse effect on cardiac rhythm
Do antiepileptic drugs cause brain damageA riskndashbenefit analysis is needed to evaluate the efficacy of anticonvulsants in stopping neonatal seizures which is poor with standard anticonvulsants as discussed above against the risk of administering the anticonvulsant drugs themselves Phenobarbitone has been reported to have adverse effects on the developing brain including inhibition of brain growth20 neuronal toxicity21 and adverse behavioural and cognitive effects into adult life when administered to young animals22 Phenytoin shows unpredictable plasma levels and potential cardiotoxicity
Recent studies have shown an effect of AED exposure on the developing brain by causing neurodegeneration23 Phenytoin administration to immature rat pups at doses which produce serum levels similar to those achieved in human neonates was associated with widespread neuronal death as a result of apop-tosis (programmed cell death) Phenobarbitone had a similar effect when a dosage regimen similar to 40 mgkg was used and
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
this effect was maximal in the more immature brain Diazepam and clonazepam also resulted in a similar effect Midazolam and lidocaine were not tested in this study The combination of phenobarbitone or phenytoin with diazepam had a particularly profound effect on neurodegeneration
In summary recent data suggest that the commonly used AEDs for neonatal convulsions may in themselves cause neuro-degeneration due to apoptosis with lasting effects on develop-ment Many babies with neonatal convulsions are treated with at least two AEDs and this may produce more severe adverse effects than the seizures themselves
Practical management of neonatal seizures
Assimilation of these data and formulation of a rational policy is difficult when faced with a fitting neonate on an intensive care unit and pressure on the medical staff to lsquodo somethingrsquo but it is important to accept that sometimes doing nothing is preferable to using potentially dangerous drugs in a situation which does not warrant such intervention Many babies who have normal interseizure neurological clinical findings and whose seizures are relatively brief and infrequent probably do not need anticon-vulsant medication A normal or near-normal background EEG trace should reassure the clinician that anticonvulsants can be withheld
Some causes of neonatal convulsions are treatable such as meningitis hypoglycaemia hypocalcaemia and inborn errors of metabolism and each baby should be rapidly and carefully investigated for cause of the convulsions
In some babies clinical assessment of seizures is difficult ie when the baby is very sick small or paralyzed Sometimes it may be difficult to assess the significance of certain movement pat-terns Under these circumstances an EEG may prove to be very helpful In many units EEG is not available out of hours and a simple aEEG or CFM is strongly advised Modern instruments are very simple to apply and prolonged or frequent seizures should be identified with only moderate training The printout can be faxed to a more senior doctor if there is doubt as to what is shown on the trace
The balance of knowledge now is that frequent seizures cause additional damage to the developing brain and that treatment to abolish the seizures is warranted Unfortunately there is little evidence that the majority of seizures can be effectively termi-nated by current standard therapy Furthermore it appears that the more abnormal the background EEG the more difficult it is to control the seizures Nevertheless a written protocol for the management of neonatal convulsions is required on each unit Phenobarbitone and phenytoin remain the mainstay of treat-ment although their effectiveness is disappointing There is little to suggest that midazolam is more effective than lidocaine as third-line therapy but lidocaine is precluded if phenytoin has been previously used
In view of the anxiety as to the neurodegenerative effects on the immature brain of most anticonvulsants used in the neonatal period (particularly when multiple drugs are used) it is prefer-able to use only one drug to maximum dosage before introduc-ing a second In addition the duration of anticonvulsants should be minimized and the drugs stopped at the earliest opportu-nity It is my practice to stop anticonvulsants prior to discharge
paeDiatRiCS anD CHilD HealtH 184 18
from hospital if the baby is neurologically normal on clinical examination
REFEREnCES
1 Ronen gm penney S andrews W the epidemiology of clinical
neonatal seizures in newfoundland a population-based study
J Pediatr 1999 134 71ndash75
2 lanska mJ lanska DJ Baumann RJ et al a population-based study
of neonatal seizures in Fayette County Kentucky Neurology 1995
45 724ndash732
3 Rennie Jm Chorley g Boylan gB et al non-expert use of the
cerebral function monitor for neonatal seizure detection Arch Dis
Child Fetal Neonatal Ed 2004 89 F37ndashF40
4 tekgul H gauvreau K Soul J et al the current etoliologic profile
and neurodevelopmental outcome of seizures in term newborn
infants Pediatrics 2006 117 1270ndash1280
5 Surtees R Wolf n treatable neonatal epilepsy Arch Dis Child 2007
92 659ndash661
6 Ben-ari y Holmes gl effects of seizures on developmental
processes in the immature brain Lancet Neurol 2006 5 1055ndash
1063
7 Holmes gl gairsa Jl Chevassus-au-louis n et al Consequences of
neonatal seizures in the rat morphological and behavioral effects
Ann Neurol 1998 44 845ndash857
8 Stafstrom Ce Chronopoulos a thurber S et al age-dependent
cognitive and behavioural deficits following kainic-acid inducing
seizures Epilepsia 1993 34 420ndash432
9 Schmid R tandon p Stafstrom Ce et al effects of neonatal seizures
on subsequent seizure-induced brain injury Neurology 1999 53
1754ndash1761
10 Hoffmann aF Zhao Q Holmes gl Cognitive impairment following
status epilepticus and recurrent seizures during early development
support for the ldquotwo-hit hypothesisrdquo Epilepsy Behav 2004 5
873ndash877
11 Wirrell eC armstrong ea osman lD et al prolonged seizures
exacerbate perinatal hypoxic-ischemic brain damage Pediatr Res
2001 50 445ndash454
12 Carmo KB Barr p Drug treatment of neonatal seizures by
neonatologists and paediatric neurologists J Paediatr Child Health
2005 41 313ndash316
13 Hall Rt Hall FK Daily DK High-dose phenobarbital therapy in term
newborn infants with severe perinatal asphyxia a randomized
prospective study with three-year follow-up J Pediatr 1998 132
345ndash348
14 Boylan gB Rennie Jm pressler Rm et al phenobarbitone neonatal
seizures and video-eeg Arch Dis Child Fetal Neonatal Ed 2002 86
F165ndash170
15 painter mJ Scher mS Stein aD et al phenobarbital compared with
phenytoin for the treatment of neonatal seizures N Engl J Med
1999 341 485ndash489
16 Singh D Kumar p narang a a randomized controlled trial of
phenobarbital in neonates with hypoxic ischemic encephalopathy
J Matern Fetal Neonatal Med 2005 18 391ndash395
17 Castro Conde JR Borges H Domenech martinez e et al midazolam
in neonatal seizures with no response to phenobarbital Neurology
2005 64 876ndash879
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
18 malingre mm Van Rooij lgm Rademaker Cma et al Development
of an optimal lidocaine infusion strategy for neonatal seizures Eur
J Pediatr 2006 165 598ndash604
19 Sankar R painter mJ neonatal seizures after all these years we still
love what doesnrsquot work Neurology 2005 64 776ndash777
20 Diaz J Schain J Bailey Bg phenobarbital-induced brain growth
retardation in artificially reared rat pups Biol Neonate 1977 32 77ndash82
21 mattson RH phenobarbital toxicity in levy RH Dreifuss Fe
mattson RH et al eds antiepipeptic Drugs 3rd edn new york
Raven 1985 p 341ndash355
22 mikati ma Holmes gl Chronopoulos a et al phenobarbital
modifies seizure-related brain injury in the developing brain Ann
Neurol 1994 36 425ndash453
23 Bittigau p Sifringer m genz K et al antiepileptic drugs and
apoptotic neurodegeneration in the developing brain Proc Natl
Acad Sci U S A 2002 99 15089ndash15094
paeDiatRiCS anD CHilD HealtH 184 182
Practice points
bull the clinician needs to be aware that almost any repetitive
stereotype movement pattern can be a manifestation of
neonatal seizures
bull eeg is important in defining neonatal seizures
bull Frequent short-lived seizures have been shown to cause long-
term neurodevelopmental problems
bull Conventional anticonvulsant medication is ineffective in
abolishing neonatal seizures in greater than 50 of cases
bull there is evidence that exposure of the neonatal brain to
multiple anticonvulsants causes neuronal death
bull Future research is needed to evaluate more effective
anticonvulsants for treating this condition
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
Emotional support for families of sick neonatesMarina nicolaou
cristine Glazebrook
AbstractParents of sick neonates experience high levels of stress anxiety and
depression Most interventions with families of sick infants have focused
on fostering the motherndashinfant relationship through the provision of
information about infant developmental needs or through increased
motherndashinfant contact Many of these studies have reported improved
maternal well-being though there are some concerns about the scope
and practicality of large-scale interventions The few studies to have
prioritized emotional support for parents of sick neonates have pro-
duced encouraging results even interventions requiring relatively few re-
sources such as telephone support parent-to-parent support and group
support have been associated with reduced psychological morbidity for
parents The needs of parents can change throughout their infantrsquos hos-
pitalization and not all want or benefit from the provision of additional
support Thus neonatal intensive care units should aim to provide a
varied flexible and sustainable programme of support options Further
research should focus on the needs of fathers
Keywords mental health neonatal intensive care parents
The admission of an infant to neonatal care is acknowledged to be a source of considerable distress for families This review aims to explore evidence for the psychological impact on families of having an infant in neonatal intensive care and to identify evi-dence for the effectiveness of interventions to promote parental well-being It will conclude with recommendations for strategies to support parents of vulnerable infants and suggestions for fur-ther research
Psychological impact of neonatal care for parents
The majority of research examining the effect on parents of having a sick neonate has focused on families of premature or low birthweight infants Such research has found that parents with a sick neonate exhibit high levels of stress compared to normative samples and to parents of healthy full-term infants1 Singer et al2 examined the stress experienced by mothers of high-risk very low birthweight (VLBW) low-risk VLBW and term
Marina Nicolaou MPhil is a Teaching Assistant at the School of
Community Health Sciences University of Nottingham Nottingham UK
Cristine Glazebrook PhD is a Professor of Health Psychology at the School
of Community Health Sciences University of Nottingham Nottingham UK
PaeDiaTrics anD cHilD HealTH 184 196
infants Several self-report measures were used including the Brief Symptom Inventory the Parenting Stress Index (PSI) the Impact on Family Scale and the Family Inventory of Life Events and Changes (FILE) Mothers of VLBW infants had more psycho-logical distress at 1 month compared to mothers of term infants Mothers of high-risk VLBW infants also reported high psycho-logical distress at 2 years and high levels of parenting stress at 3 years Mothers have also been found to have higher stress levels compared to fathers Shaw et al3 examined the prevalence of acute stress disorder (ASD) in 40 parents whose infants were in the neonatal intensive care unit (NICU) Nearly half of the moth-ers (44) met the criteria for ASD although none of the fathers did Furthermore the severity of the symptoms (measured by the number of concurrent symptoms) was greater for the moth-ers than for the fathers3 The reasons behind this difference have been widely speculated with some believing that it is due to the mothersrsquo greater psychological involvement with the infant as evidenced by their general greater vulnerability to postpartum psychological disorder It could also reflect gender differences in coping style
Having an infant who requires intensive medical care repre-sents a significant emotional burden for families Not only is there extreme anxiety surrounding the infantrsquos health and distress for the childrsquos suffering there is also the unfamiliar and intimidating environment of the NICU to adjust to Hopper in her review of the literature identified sources of stress for parents of sick neo-nates as falling into three areas4 Situational factors included the severity of the infantrsquos illness and how parents adapted to the life crisis of having a sick infant Personal factors involved parental emotions about their roles and the instrumental and informa-tional support which were available to them The third area was classified as environmental sources of stress and included the environment of the NICU and the relationship between parents and members of staff This relationship has been examined by several studies in the nursing literature nurses are seen as ide-ally placed to provide the necessary support and information to parents with sick neonates However whilst some studies have shown that supportive and helpful hospital staff can have a posi-tive effect on parents other studies have highlighted the prob-lems and difficulties which can manifest It has been shown that parents and nurses often have very different ideas about issues eg the necessary skills and competencies needed in an NICU or the characteristics that make a lsquogood motherrsquo
Research has shown that there may be a relationship between high levels of parental stress and an increased likelihood of depression5 Postpartum depression is a psychiatric illness which appears in 10ndash15 of postpartum women Its reported preva-lence rates however have ranged from less than 10 up to 306 depending on the instruments used the population exam-ined and the timing of the research Several factors have been found to be associated with postpartum depression including poor social support and infant-related stressors6 Evidence indi-cates that postnatal depression may be underreported and this is of concern since the mental and psychological health of the mother can affect her relationship with her infant and thus the infantrsquos cognitive and emotional development5 Depressed moth-ers appear to look touch and talk to their infants less frequently and also appear to show fewer positive and more negative faces7 The vocalizations of mothers suffering with depression have also
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
been found to be less effective at promoting cognitive growth and learning in infants8
If researchers are interested in finding ways of providing sup-port for families of sick neonates then they must listen to what such families perceive their needs to be in order to avoid increas-ing anxiety and distress Furthermore the provision of appropri-ate support be it emotional informational or social will enhance parental coping abilities increase self-esteem and reduce anxiety It should be noted though that the research conducted around these issues has often taken lsquosupport needsrsquo as being synony-mous with lsquoinformation needsrsquo Such studies have examined the type the amount and quality of information that parents receive and perceive themselves as needing but have not explored in equal depth the perceived emotional support needs of families who have a sick infant In addition the needs of parents may change throughout their infantrsquos illness Ward examined the per-ceived needs of 52 parents of infants in an NICU9 Parents rated the needs of their hospitalized infant as most important along with the need to be reassured Interestingly they ranked their support needs as least important This research was conducted during the first week of the infantsrsquo hospitalization however which would explain the preoccupation of the parents with the infantrsquos health These results demonstrate that if researchers want to find ways of providing emotional support to parents of sick neonates they must be prepared not only to listen to parents but also to be flexible enough to satisfy the parentsrsquo changing needs and expectations
Interventions aimed at supporting parents
Most interventions that been evaluated in controlled studies have focused on supporting the motherndashinfant relationship and provid-ing information on infant development Many of these interven-tions have included the aim of improving the parental emotional state and thus psychological outcomes such as stress or anxi-ety have been assessed However few studies appear to include fathers This means that strategies implemented to provide emo-tional support to families of sick neonates are often derived from interventions tailored for mothers even though fathers may have different emotional needs
A wide range of interventions with mothers and infants has been evaluated in the NICU Increasing motherndashinfant contact through kangaroo care has been found to reduce maternal anxiety1011 and educational programmes delivered to fami-lies in the NICU have also been associated with reduced emo-tional difficulties in parents12ndash14 Kaaresen and colleagues implemented an intervention which consisted of eight sessions before discharge and four home visits all by trained nurses The sample included 71 premature infants in the intervention group 69 premature infants in the control group and 74 infants in the full-term control group The randomized controlled trial found that the intervention reduced parenting stress in both mothers and fathers of premature infants compared to controls to a level equivalent to parents in the term control group13 At 6 months corrected age mothers of preterm infants who had not received the intervention had total PSI scores which were 17 points higher than the mothers of infants born at term (an effect size of 057) A similar study evaluated the efficacy of an educationalndashbehavioural programmendashCreating Opportunities for
PaeDiaTrics anD cHilD HealTH 184 19
Parent Empowerment (COPE) ndash through a randomized controlled trial with 260 families of premature infants14 COPE was a four-phase educationalndashbehavioural programme which began as early as 2ndash4 d after mothers had given birth and continued until 1 week after discharge from the NICU The programme consisted of audiotaped and written infant behaviour information along with photographs which focused on common behaviours and characteristics of premature infants It also included various par-ent activities in the form of a four-phase workbook which aimed to assist mothers in the implementation of the experimental infor-mation COPE was found significantly to reduce maternal stress in the NICU as well as maternal anxiety and depressive symptoms after hospitalization In contrast a cluster randomized trial of a parenting intervention delivered to mothers of very premature infants from soon after birth showed no benefits for parenting stress1 The authors hypothesized that the intervention had not been of sufficient intensity particularly in the weeks surrounding discharge Neonatal care presents a significant barrier to parent-ing in the early weeks following a very preterm birth and so inter-ventions which focus on the developmental needs of infants and the parentndashchild relationship should particularly aim to support parents as they take on the parenting role There was also concern that the intervention had failed to reach those most at risk
Since large-scale projects can be costly to implement and may often fail to reach the families in most need it may be wiser to focus on intervention programmes which are more practical and easier to implement within a neonatal care setting Research has shown that even interventions which are based on one-off meet-ings with parents of sick neonates can be effective Jotzo and Poets examined the effect of an intervention programme aimed at reducing the severity of traumatic responses as a result of giv-ing birth prematurely15 Their programme consisted of a one-off intervention meeting along with additional psychological help throughout the hospitalization of the infant The meeting cov-ered a variety of issues including a reconstruction of the events shortly before and after the infantrsquos birth relaxation techniques discussion of coping strategies available resources and social support and support during emotional outbursts The measures used included the Impact of Event Scale (IES) and the Peritrau-matic Dissociative Experience Questionnaire At discharge the mothers who received the intervention were found to have a significantly lower traumatic impact as a result of premature birth Furthermore fewer mothers in the intervention group showed symptoms of clinically significant psychological trauma at discharge compared to mothers in the control group (36 vs 76)15 The lsquoParents Circle Programrsquo is another intervention with a similar structure16 This consisted of a 90 min session for parents with the aim of enhancing the developing relationship between parents and infants and to offer parents support A total of 104 parents (59 mothers and 45 fathers) and 44 members of hospital staff were asked to evaluate the programme and their results were analysed using content analysis Families reported gaining perspective on their situation feeling supported becom-ing aware of cues and optimizing interactions and becoming aware of available resources Parents and staff alike felt that participating in the intervention helped parents overcome the difficulties associated with the early time of their infantrsquos hos-pitalization Additional studies have also found positive results with fairly minimal interventions including discussion groups
7 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
in the NICU music during kangaroo care and pairing mothers of sick neonates with trained mothers who had been through similar experiences
Parent support programmes
Parent support programmes (PSPs) which are based in NICUs can provide parents with the opportunity to talk to parents who have been in similar situations and also to discuss their emo-tions with professionals who can help them cope with their situa-tion111718 The parent-to-parent support programme for mothers of preterm infants evaluated by Preyde and Ardal included edu-cational parental support group meetings and individual par-ent-to-parent support (primarily telephone support)19 Measures used included the Parental Stressor Scale NICU the State and the Trait Anxiety Inventories and the Beck Depression Inven-tory After 4 months of participation mothers in the intervention group reported lower levels of stress state anxiety and depres-sion compared to control group mothers The authors speculated however that the participants who were able to meet face to face with other parents were those who benefited the most Hurst conducted a comprehensive survey of an NICU-based PSP This PSP was provided in a variety of formats including a weekly parent support group hospital visitation and 24-h telephone sup-port20 Of the 477 participants 303 families used the PSP dur-ing a 2-year evaluation period with 78 using only one form of support and 18 using two forms Of a sub-sample of 48 parents asked to complete an evaluation of the PSP 92 stated that they would recommend such a programme to other parents Furthermore the majority of parents felt that it made them feel supported and helped them deal with their emotions20 This is an indication that such programmes can be very successful in sup-porting parents throughout their infantrsquos hospitalization It also shows that it can be beneficial to give parents several options and formats when it comes to such support services It is impor-tant to consider though that both the Hurst and the Preyde and Ardal studies found that some participants did not find the sup-port programmes helpful even reporting that they had caused them increased stress and anxiety Therefore it should not be assumed that support programmes will suit every individual and will provide the required support for all parents1920 NICUs need to be flexible enough to provide parents with a range of forms of support to choose from
The increased understanding of the strains that parents of sick neonates have to deal with has also led to efforts to improve customary practices in NICUs Family-centred care focuses on infants and their needs and attempts to redefine the relationship between parents and caregivers These practices strive to provide parents with support during their infantrsquos illness by focusing on freely sharing information and on the collaboration between parents and hospital staff Family-centred care has been found to be associated with several beneficial outcomes including improved parental satisfaction increased parental comfort staff satisfaction and decreased parental stress18 Research is already examining these practices and questioning how these can be improved further Such research reflects the increasing effort focused on lsquohumanizingrsquo the environment in NICUs in order to make parents feel more comfortable about spending time with their infants
PaeDiaTrics anD cHilD HealTH 184 19
Conclusion
Surprisingly few interventions have prioritized the provision of emotional support for parents of sick neonates or accounted for the changing needs and wishes of parents over the course of their infantrsquos care Large-scale supportive education-based inter-ventions have been shown to be effective in reducing parental distress However the feasibility and sustainability of such pro-grammes should also be considered Programmes which require significant additional resources can be expensive and there are also issues of training and quality control Interventions which require significant input from parents may also place additional burdens on families making them potentially less accessible to those most at risk Arguably the aim should be to explore ways of providing acceptable and effective informational support which could be complemented by emotional support from health professionals and from other parents in the unit Increasingly studies are exploring the use of computers and multimedia as an engaging flexible and cost-effective method of targeting indi-vidual needs and providing support and information Such com-puter-based and interactive multimedia interventions have been found to be successful with a range of patient groups and could therefore be examined as a complementary method of providing informational support to families with sick neonates
REfEREnCEs
1 Glazebrook c Marlow n israel c et al randomised trial of a
parenting intervention during neonatal intensive care Arch Dis Child
Fetal Neonatal Ed 2007 92 F438ndash443
2 singer lT salvator a Guo s collin M lilien l Baley J Maternal
psychological distress and parenting stress after the birth of a very
low-birth-weight infant JAMA 1999 281 799ndash805
3 shaw rJ Deblois T ikuta l Ginzburg K Fleisher B Koopman c
acute stress disorder among parents of infants in the neonatal
intensive care nursery Psychosomatics 2006 47 206ndash212
4 Hopper a sources of stress for parents of a sick neonate a
literature review Pediatr Nurs 2000 30 29ndash32
5 Davis l edwards H Mohay H wollin J The impact of very
premature birth on the psychological health of mothers Early Hum
Dev 2003 73 61ndash70
6 Bernazzani O saucier J-F David H Borgeat F Psychosocial
predictors of depressive symptomatology level in postpartum
women J Affect Disord 1997 46 39ndash49
7 Field T infants of depressed mothers Infant Behav Dev 1995 18
1ndash13
8 Kaplan Ps Bachorowski J-a Zarlengo-strouse P child-directed
speech produced by mothers with symptoms of depression fails
to promote associative learning in 4-month-old infants Child Dev
1999 70 560ndash570
9 ward K Perceived needs of parents of critically ill infants in
a neonatal intensive care unit (nicU) Pediatr Nurs 2001 27
281ndash286
10 lai Hl chen cJ Peng Tc et al randomized controlled trial of music
during kangaroo care on maternal state anxiety and preterm infantsrsquo
responses Int J Nurs Stud 2006 43 139ndash146
8 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
11 Tallandini Ma scalembra c Kangaroo mother care and mother-
premature infant dyadic interaction Infant Ment Health J 2006 27
251ndash275
12 Ohgi s Fukuda M akiyama T Gima H effect of an early intervention
programme on low birthweight infants with cerebral injuries
J Paediatr Child Health 2004 40 689ndash695
13 Kaaresen Pi ronning Ja Ulvund se Dahl lB a randomized
controlled trial of the effectiveness of an early-intervention program
in reducing parenting stress after preterm birth Pediatrics 2006
118 e9ndash19
14 Melnyk BM Feinstein nF alpert-Gillis l et al reducing premature
infantsrsquo length of stay and improving parentsrsquo mental health
outcomes with the creating opportunities for parent empowerment
(cOPe) neonatal intensive care unit program a randomized
controlled trial Pediatrics 2006 118 e1414ndash1427
15 Jotzo M Poets cF Helping parents cope with the trauma of
premature birth an evaluation of a trauma-preventive psychological
intervention Pediatrics 2005 115 915ndash919
16 Pearson J andersen K evaluation of a program to promote positive
parenting in the neonatal intensive care unit Neonatal Netw 2001
20 43ndash48
17 roman l lindsay J Boger r et al Parent-to-parent support
initiated in the neonatal intensive care unit Res Nurs Health 1995
18 385ndash394
18 Meyer ec coll cTG lester BM Boukydis cFZ McDonough sM Oh w
Family-based intervention improves maternal psychological well-
being and feeding interaction of preterm infants Pediatrics 1994
93 241ndash246
PaeDiaTrics anD cHilD HealTH 184 19
19 Preyde M ardal F effectiveness of a parent ldquobuddyrdquo program for
mothers of very preterm infants in a neonatal intensive care unit
CMAJ 2003 168 969ndash973
20 Hurst i One size does not fit all Parentsrsquo evaluations of a support
program in a newborn intensive care nursery J Perinat Neonatal
Nurs 2006 20 252ndash261
Practice points
bull Parents of sick neonates experience significant distress and
exhibit higher levels of stress anxiety and depression than
parents of healthy infants
bull educational support emotional support and increased
motherndashinfant contact have been shown to promote maternal
well-being
bull emotional support for fathers has been largely neglected in
the research literature
bull Parents benefit from a choice of supportive facilities which
could include face-to-face sessions with health professionals
telephone support hospital visitation parent-to-parent
support and unit-based group support meetings
bull Parentsrsquo support needs can change during their infantrsquos
hospitalization and not all parents want or benefit from the
provision of additional information and emotional support in
the neonatal unit
9 copy 2008 elsevier ltd all rights reserved
Personal Practice
When should enteral feeds be started in preterm infantsnicholas D embleton
AbstractPaediatricians are regularly faced with the question of when best to start
enteral feeds in preterm infants this is important as longer term out-
come may be compromised by sub-optimal nutrition in early life clinical
factors that may affect the decision to start and the risk and benefits
are discussed
Keywords breast milk feeding nutrition parenteral nutrition
Key points in the history
Alice is lsquonutritionally vulnerablersquo and whilst this may not be immediately apparent it will affect her long term outcome Her energy stores are extremely limited and consist primarily of pro-tein She has less than 5 fat and little energy associated with stored glycogen She is losing about 1 gkgd protein equivalent so she needs at least that and a minimum of 50ndash60 kcalkg of energy just to maintain the status quo let alone grow
Her weight is on the 25th centile Review of any antenatal his-tory may reveal whether fetal growth was normal Fetal growth retardation can occur with a weight greater than 10th centile The presence of antenatal absent or reversed end diastolic flow in the umbilical artery indicates poor gut blood flow This increases the risk of necrotizing enterocolitis (NEC) and might suggest a more cautious approach to starting feeds1
She has no important cardiovascular problems but if she were hypotensive gut blood flow may be low There is no umbilical
Nicholas D Embleton BSC (Hons) MBBS (Hons) MD FRCPCH is Consultant in
Neonatal Medicine at Newcastle Neonatal Service Royal Victoria
Infirmary Newcastle upon Tyne NE1 4LP UK
Should you start feeds at a day of age
alice was born following spontaneous labour at 30 weeksrsquo
gestation she weighed 1300 g and is now 18 h old she was
briefly ventilated and then extubated to continuous positive
airway pressure 12 h ago in 35 oxygen she has had caffeine
citrate but still has intermittent episodes of self-correcting
apnoea she was commenced on iv 10 dextrose but this was
replaced by a parenteral amino acid solution (referred to as
lsquotPnrsquo) along with intralipid at 0900 this morning serum glucose
is 11 mmoll and blood pressure is 42 systolic
PaeDiatrics anD cHilD HealtH 184 20
arterial catheter in situ but there is no good evidence that this should delay the decision to start feeds Her glucose is high but this is quite common in a baby like this Could this be a sign of sepsis Caffeine does not affect the incidence of NEC2 The great-est risk factor for NEC in this case is prematurity
What else might be found on examination
Up until 24 h ago she was swallowing large amounts of amniotic fluid What will have changed since then
General examination should confirm peripheral perfusion lsquogestaltrsquo view (does she look lsquowellrsquo) and cardiovascular status lsquoBowel soundsrsquo are not usually helpful
The most important variable likely to affect gut perfusion is the arterial duct Precordial lsquoheaversquo and a loud murmur are sug-gestive but it is possible to have a significant ductal shunt in a baby with a normal examination Cardiac ultrasound will con-firm this diagnosis It might be better to treat a large shunt first with indometacin and to delay starting feeds for a further 24 h
It is not possible to assess gut perfusion clinically but normal perfusion elsewhere (adequate urine output usually indicates adequate renal perfusion) would be reassuring Most preterm babies have a few abdominal lsquoloopsrsquo visible but a distended abdomen with many palpable loops suggests ileus This might be secondary to sepsis or poor gut blood flow Preterm babies do not pass much meconium in the first 24ndash48 h
Balance of risks between starting and withholding feeds
Alice requires 35ndash4 gkgd of protein and 120 kcalkgd to grow3 This will initially be provided parenterally Delaying feeds increases the risk of gut villous atrophy and prolongs the need for lsquototal parenteral nutrition (TPN)rsquo TPN requires intravenous access and so increases the risk of sepsis and when prolonged use is required combined with the lack of enteral feeding may result in hepatic impairment
Delaying feeds may allow a gut that has been chronically under-perfused to re-establish more normal perfusion although normal gut endocrine function digestive enzyme upregulation and motility require a source of intraluminal nutrients1 A recent study suggested benefit from delaying the introduction of feeds4 but methodologi-cal problems exist5 Although a Cochrane meta-analysis suggested no benefit only two studies were included6 A large UK-based trial is examining the effect of early or late feeding in preterm infants who were born growth retarded following identification of antena-tal absent or reversed end diastolic flow in the umbilical artery7
When starting feeds what volume should be used
There are no good data to guide this decision We start with 24 mlkg (1 mlkgh) and then increase by this amount each day Most babies achieve full enteral feeds (ge150 mlkgd) by a week of age Feeding guidelines improve the outcome8 Measure-ment or assessment of gastric aspirates is not consistently useful in predicting subsequent feeding intolerance or development of NEC Aspirate volumes equivalent to or sometimes greater than the amount given in the preceding 1ndash2 h are usually normal Most aspirates have a greenish colour Thick bloody or intensely bile-stained aspirates require detailed assessment
0 copy 2008 elsevier ltd all rights reserved
Personal Practice
What else affects decisions and outcome
Feeding success is affected by sepsis and NEC Scrupulous atten-tion should be paid to hand washing and intravenous access and blood sampling should be minimized There is no good evidence to support the routine use of pro-kinetic agents or H2 blockers
The most important clinical intervention affecting the occur-rence of NEC is the use of breast milk9 All efforts should be directed at persuading parents of the benefits and supporting the process Some clinicians delay starting feeds for a further 24 h whilst expressed breast milk becomes available Donor breast milk might be equally efficacious10
RefeRenceS
1 Dorling J Kempley s leaf a Feeding growth restricted preterm
infants with abnormal antenatal Doppler results Arch Dis Child Fetal
Neonatal Ed 2005 90 F359ndash363
2 schmidt B roberts rs Davis P et al caffeine therapy for apnea of
prematurity N Engl J Med 2006 354 2112ndash2121
PaeDiatrics anD cHilD HealtH 184 20
3 embleton nD Pang n cooke rJ Postnatal malnutrition and growth
retardation an inevitable consequence of current recommendations
in preterm infants Pediatrics 2001 107 270ndash273
4 Berseth cl Bisquera Ja Paje VU Prolonging small feeding volumes
early in life decreases the incidence of necrotizing enterocolitis in
very low birth weight infants Pediatrics 2003 111 529ndash534
5 Menon G Boyle eM embleton nD et al introduction of enteral
feeds in preterm infants Pediatrics 2004 114 327ndash328
6 Kennedy Ka tyson Je chamnanvanikij s early versus delayed
initiation of progressive enteral feedings for parenterally fed low
birth weight or preterm infants Cochrane Database Syst Rev 2000
cD001970
7 wwwnpeuoxacukadept
8 Patole sK de Klerk n impact of standardised feeding regimens on
incidence of neonatal necrotising enterocolitis a systematic review
and meta-analysis of observational studies Arch Dis Child Fetal
Neonatal Ed 2005 90 F147ndash151
9 lucas a cole tJ Breast milk and neonatal necrotising enterocolitis
Lancet 1990 336 1519ndash1523
10 Boyd ca Quigley Ma Brocklehurst P Donor breast milk versus
infant formula for preterm infants systematic review and meta-
analysis Arch Dis Child Fetal Neonatal Ed 2007 92 F169ndash175
1 copy 2008 elsevier ltd all rights reserved
self-assessment
Case 1A term male infant born to consanguineous parents is assessed at 24 h of age due to poor feeding profuse yellow watery diar-rhoea and irritability He weighed 32 kg at birth and delivery was uneventful There was no polyhydramnios He has been breastfed since birth On examination he is pale with a non-tender but distended abdomen and reduced bowel sounds His weight is 275 kg and he looks dehydrated Examination is otherwise normal
Initial investigations (normal values in parentheses) showed
sodium 149 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 65 mmollitre (25ndash75)
creatinine 147 μmollitre (40ndash110)
chloride 119 mmollitre (95ndash105)
haemoglobin 172 gdl (140ndash200)
White blood cell count 80 times 109litre (100ndash260)
Platelet count 302 times 109litre (150ndash400)
arterial blood gas
ph 720 (730ndash745)
PcO2 23 kPa (46ndash60)
Bicarbonate 68 mmollitre (220ndash260)
Base excess minus186 mmollitre (minus20 to +20)
lactate 59 mmollitre (06ndash24)
An abdominal X-ray shows distended bowel loops with no intramural thickening or pneumoperitoneum (Figure 1)
He was given nil by mouth and received intravenous fluids and antibiotics His dehydration improved but the metabolic acidosis and diarrhoea persisted despite receiving no enteral feeds and the commencement of total parenteral nutrition Blood and stool cultures were negative
1 Which of the following best describes these results Choose ONE answer ONLY from the followingA Hypernatraemia hyperchloraemic metabolic acidosis
with increased anion gapB Hypernatraemia hyperchloraemic metabolic acidosis
with normal anion gap
Manish Sadarangani BM BCh MA MRCPCH is Clinical Research Fellow
at the Department of Paediatrics University of Oxford Centre for
Clinical Vaccinology and Tropical Medicine Churchill Hospital
Oxford OX3 7LJ UK
Shabna Rajapaksa MB BChir MA MRCPCH is Specialist Registrar in
Paediatrics at the Paediatric Intensive Care Unit John Radcliffe
Hospital Oxford OX3 9DU UK
Nicholas Mann MD FRCP FRCPCH DCH is Consultant Paediatrician at the
Department of Paediatrics Royal Berkshire Hospital Reading RG1
5AN UK
self-assessment
C Hypernatraemic dehydration and compensated metabolic acidosis
D Acute renal failureE Renal tubular acidosis
2 What is the likely diagnosis Choose ONE answer ONLY from the followingA Hirschsprung disease ndash long segmentB Cystic fibrosis with meconium ileusC Microvillus inclusion diseaseD Cowrsquos milk protein intoleranceE Lactose intolerance
3 What is the investigation of choice Choose ONE answer ONLY from the followingA Rectal biopsy with staining for acetylcholine receptorsB Immunoreactive trypsinC Gastrointestinal endoscopy and biopsyD Stool microscopy and cultureE Stool reducing substances
Case 2A 4-year-old boy presents with a 3 d history of jaundice and a florid rash He has had orange urine and there is no change in his stool colour His family originate from Kosovo and have lived in the UK for the last 8 years He has never left the UK There is no history of blood transfusion or sex-ual abuse The grandmother was recently diagnosed with hepatitis B
On examination he is well apyrexial and mildly jaundiced with cervical and axillary lymphadenopathy He has an exten-sive papular rash over the face extremities and trunk (Figure 2) There is 3 cm hepatomegaly with no splenomegaly or ascites Examination is otherwise normal
Figure 1 abdominal X-ray of baby
Paediatrics and child health 184 202 copy 2008 elsevier ltd all rights reserved
self-assessment
Initial investigations are as follows
haemoglobin 110 gdl (113ndash135)
White blood cell count 108 times 109litre (50ndash150)
Platelet count 278 times 109litre (150ndash400)
inr 10 (08ndash12)
aPt ratio 10 (08ndash13)
sodium 140 mmollitre (135ndash145)
Potassium 42 mmollitre (35ndash50)
Urea 56 mmollitre (25ndash75)
creatinine 65 μmollitre (45ndash120)
total bilirubin 66 μmollitre (0ndash15)
conjugated bilirubin 23 μmollitre (0ndash10)
alanine aminotransferase (alt) 2033 iUlitre (0ndash35)
alkaline phosphatase 987 iUlitre (71ndash234)
Gamma-glutamyl transferase (GGt) 870 iUlitre (0ndash51)
1 What is the name of this rash Choose ONE answer ONLY from the followingA Erythema multiformeB Erythema migransC GianottiminusCrosti syndromeD EczemaE Dermatitis herpetiformis
2 What is the most likely diagnosis Choose ONE Answer ONLY from the followingA Autoimmune hepatitisB Hepatitis BC Hepatitis DD Wilson diseaseE Alpha-1 antitrypsin deficiency
3 What is the best means of management Choose ONE answer ONLY from the followingA Isolation until the jaundice disappearsB ImmunosuppressionC Copper chelating agents and genetic counsellingD Patient and family education with consideration of
antiviral agentsE Liver transplantation
Case 3A 10-month-old boy presents with 3 weeks of vomiting and constipation ndash he is passing hard stools every 2ndash3 days He has fallen from the 9th to below the 04th centile in the last 6 weeks He passed meconium within the first 24 h of life On examina-tion he looks pale and there are some dysmorphic features ndash a short nose long philtrum and wide mouth He has normal heart sounds with a grade 3 ejection systolic murmur loudest at the upper right sternal edge Examination is otherwise normal
Initial investigations are as follows
haemoglobin 91 gdl (113ndash141)
total white blood cell count 124 times 109litre (60ndash170)
Platelet count 407 times 109litre (150ndash400)
sodium 144 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 78 mmollitre (25ndash75)
creatinine 78 μmollitre (45ndash120)
albumin 52 glitre (35ndash50)
corrected calcium 384 mmollitre (238ndash263)
Phosphate 167 mmollitre (099ndash157)
1 What is the most likely diagnosis Choose ONE answer ONLY from the followingA HyperparathyroidismB Acute leukaemiaC Williams syndromeD Hypervitaminosis DE Familial hypocalciuric hypercalcaemia
2 Which investigation would be most useful in establishing the diagnosis Choose ONE answer ONLY from the followingA Intact parathyroid hormone assayB Blood filmC Fluorescent in-situ hybridization for 7q1123 deletionD 25-hydroxyvitamin D assayE Urine calciumcreatinine ratio
3 Which of the following treatments would not be suitable for this patient Choose ONE answer ONLY from the followingA Low calcium dietB Normal saline infusionC FurosemideD CorticosteroidsE Bisphosphonates
Case 4A 10-week-old girl presents with a 2-day history of poor feed-ing Her mother has been concerned about weakness since birth She only has a flicker of movement in the arms none in the legs and has a weak cry She has been passing urine and opening her bowels normally She was born at full term by normal delivery and did not require any resuscitation at birth Normal fetal movements were felt antenatally and there was no polyhydramnios She is the first child of non- consanguineous parents and there is no significant family his-tory On examination she is alert and fixing and following appropriately She has a weak cry and a weak suck There is reduced central and peripheral tone with marked head lag
Figure 2 rash found on examination
Paediatrics and child health 184 203 copy 2008 elsevier ltd all rights reserved
self-assessment
Muscle power is grade 3 out of 5 in the arms and legs There is no muscle or tongue fasciculation and she has absent reflexes throughout The remainder of the examination is normal
Electromyogram shows irregular polyphasic motor unit potentials with marked instability consistent with a dener-vating and re-innervating process (Figure 3)
1 Which of the following additional investigations may be helpful Choose ONE answer ONLY from the followingA Nerve conduction studiesB Creatine kinase assayC Muscle biopsyD SMN1 gene analysisE All of the above
2 What is the most likely cause of this childrsquos symptoms Choose ONE answer ONLY from the followingA Congenital myotonic dystrophyB Duchenne muscular dystrophyC PraderminusWilli syndromeD Spinal muscular atrophyE Mitochondrial myopathy
3 What is the mode of inheritance of this disease Choose ONE answer ONLY from the followingA X-linked recessiveB Autosomal recessiveC Autosomal dominantD MitochondrialE Sporadic
Case 5A 13-year-old girl presents with a 3-week history of fever up to 40degC night sweats and headache She has a reduced appetite with some weight loss She has no other specific symptoms She was on holiday in China 7 months ago On examination she looks well and has a temperature of 387degC There is no lymphadenopathy and no rashes Examination is entirely normal
Results of investigations are as follows
haemoglobin 126 gdl (120ndash160)
total white blood cell count 132 times 109litre (43ndash108)
neutrophil count 115 times 109litre (25ndash75)
Platelet count 244 times 109litre (150ndash400)
Blood film neutrophilia with left shift
erythrocyte sedimentation rate 63 mmh (1ndash20)
c-reactive protein 219 mglitre (0ndash5)
Blood culture Streptococcus intermedius
from anaerobic bottle only
csf culture negative
Magnetic resonance imaging (MRI) of the brain shows acute frontal sinusitis with a large intracranial frontal extra-dural empyema (Figure 4)
1 Which of the following would be appropriate management Choose ONE answer ONLY from the followingA A 12-week course of intravenous antibioticsB Drainage of the frontal sinus followed by 2 weeks of
intravenous antibioticsC Drainage of the empyema followed by 2 weeks of
intravenous antibioticsD Drainage of the empyema and the frontal sinus
followed by 2 weeks of oral antibiotics
1151
1152
1153
1154
1155
1156
1157
1158
1159
1200
50ms 1mV
Figure 3 electromyogram recording from the patient Figure 4 Parasagittal section from mri scan of patient
Paediatrics and child health 184 204 copy 2008 elsevier ltd all rights reserved
self-assessment
E Drainage of the empyema and the frontal sinus followed by 8 weeks of intravenous antibiotics
2 Streptococcus intermedius is a potential pathogen in which of the following infections Choose ONE answer ONLY from the followingA Liver abscessB Urinary tract infectionC MeningitisD Thoracic empyemaE Pneumonia
3 Which of the following statements regarding lsquopyrexia of unknown originrsquo in children is false Choose ONE answer ONLY from the followingA Malignancy is the underlying pathology in 5ndash15 of
casesB An aetiology will be found in over 90 of casesC The most common cause is infectionD A rheumatological cause is found in 10ndash20 of casesE Familial Mediterranean fever can occur in children of
non-Mediterranean ethnicity
Answers
Case 11 AThe anion gap is a useful tool to differentiate the causes of a metabolic acidosis It is calculated by the equation
Anion gap = [Na K ] [Cl HCO ]3+ + minus minus+ minus +
It represents the effect of unmeasured anions on the plasma pH and is normally 10ndash18 mmollitre
2 CMicrovillus inclusion disease is a severe autosomal recessive enteropathy that is typically apparent within hours or days after birth It is the second most common cause of protracted diarrhoea in the newborn after infectious causes It is characterized by severe yellow watery diarrhoea and malabsorption due to hypoplasia andor atrophy of the villi of the small intestine secondary to an inherited defect in the brush border membrane This results in severe dehydration malnutrition and metabolic acidosis due to bicarbonate loss from the gut
3 CDiagnosis of microvillus inclusion disease is made on small bowel biopsy Electron microscopy findings are of intracellular brush border inclusions and densely packed apical cytoplasmic vesicular bodies indicating microvillous atrophy There is no cure Treatment is supportive with total parenteral nutrition and consideration of small bowel transplantation
Further reAding
Goulet O ruemmele f causes and management of intestinal failure
in children Gastroenterology 2006 130(suppl 1) s16ndash28
rhoads Jm Vogler rc lacey sr et al microvillus inclusion disease
In vitro jejunal electrolyte transport Gastroenterology 1991
100 811ndash817
Case 21 CGianottindashCrosti syndrome is a distinct self-limiting rash commonly associated with viral infections in children between 2 and 6 years of age It presents as multiple pink to redminusbrown papules or papulovesicles which may be pruritic and can become confluent Gianotti and Crosti initially described the exanthema as associated with hepatitis B virus and they termed it papular acrodermatitis of childhood It can occur in several viral diseases eg hepatitis A B and C coxsackie viruses and cytomegalovirus
2 BHepatitis is a syndrome characterized by inflammation or injury of liver cells which may develop into cell necrosis and subsequently fibrosis andor cirrhosis Biochemically there are raised liver enzymes The degree of transaminase elevation does not correlate with the severity of the disease process Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of viral hepatitis
3 DHepatitis B infection is transmitted via blood sexually or vertically Infection may be acute or chronic Diagnostic markers are the presence of surface antigen (HBsAg) and HBV DNA The presence of e antigen (HBeAg) indicates high infectivity Infected newborns have a 95 risk of becoming carriers this risk decreases with infection acquired later in childhood Approximately 15ndash25 of HBV carriers will die from cirrhosis or hepatocellular carcinoma Extrahepatic findings are more common in older children and include membranous glomerulonephritis and GianottiminusCrosti syndrome Fulminant hepatic failure occurs in severe cases resulting in persistent jaundice encephalopathy and coagulopathy Management includes counselling family members monitoring for ongoing liver disease and consideration of antiviral therapy
Further reAding
Brandt O abeck d Gianotti r Burgdorf W Gianotti crosti
syndrome J Am Acad Dermatol 2006 54 136ndash145
slowik mK Jhaveri r hepatitis B and c viruses in infants and
young children Semin Pediatr Infect Dis 2005 16 296ndash305
Case 31 CHypercalcaemia is uncommon in infancy The most common symptoms in this age group are irritability vomiting and constipation It may be a manifestation of Williams syndrome vitamin D or calcium excess as well as disorders associated with reduced bone formation such as hypophosphatasia or increased bone resorption such as malignancy Occasionally
Paediatrics and child health 184 205 copy 2008 elsevier ltd all rights reserved
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-
SympoSium neonatology
Endotracheal intubationThe placement of an endotracheal tube has long been the gold standard of airway control and this remains true in the unconscious baby if it is correctly sized placed and fixed in a timely manner However experience is directly related to effec-tiveness in endotracheal intubation1819 and the success rate of less experienced clinicians such as a resident (STA1-3) or a fel-low (STA3-5) is lower varying between 33 and 68 Even senior neonatologists often take longer than guidelines recom-mend19 Experienced clinicians may judge correct endotracheal position visually or by an increase in heart rate with the first breaths but detection of exhaled carbon dioxide will give more rapid confirmation in larger babies12171920 and this can be par-ticularly useful for less experienced clinicians or those supervis-ing them However not all systems for the detection of exhaled carbon dioxide work in the smallest premature infants
Laryngeal masksLaryngeal masks may be effective for ventilating term newborn babies but there are few data for small premature infants There have been reports of dislodged laryngeal airways during paedi-atric arrests when chest compressions have been administered Although success of placement at first attempt by paediatri-cians is greater with a laryngeal mask than with an endotra-cheal tube21 the only and small randomized controlled trial in the delivery room favoured endotracheal intubation when per-formed by an anaesthetist22 Based mainly upon case reports the laryngeal mask can be recommended when positioning and mask ventilation and endotracheal intubation have failed to secure the airway but not as yet as a primary method of airway control
MeconiumIn 2000 Wisewell et al23 reported a large randomized controlled trial showing that tracheal intubation and suctioning of meco-nium-stained but vigorous babies at birth did not reduce the incidence or severity of meconium aspiration syndrome More recently another randomized trial has now shown that suction-ing on the perineum similarly offers no benefit24 Neither of these practices is recommended but intubation and suction of meconium from the trachea of non-vigorous babies born through meconium-stained liquor is still recommended
Breathing
In the apnoeic baby the first breaths establish the resting lung volume and aerate the fluid-filled alveoli This mechanical effect aided by surface tension within the alveoli causes the initial fall in pulmonary vascular resistance Experimentally this effect occurs even if the lungs are ventilated with nitrogen but is increased when air is used presumably due to the vasodilator effect of 21 oxygen The mechanical stretching of the lung also triggers the activation of cyclo-oxygenase beginning the production of prostacyclin Bradykinin is produced which has a further direct vasodilator effect and also possibly via prostacyclin Therefore adequate airway control and passive ventilation is vital not only because babies requiring resuscitation at birth have an almost uniformly respiratory aetiology but also in order to promote post-natal adaptation and reverse any maladaptation
paeDiatRiCS anD CHilD HealtH 184 16
In term babies peak ventilatory pressures of 20ndash30 cmH2O may be required but the minimal pressure needed to achieve an improvement in heart rate should be used or if there is no response chest wall movement Longer breaths at lower pressure may be more effective in displacing alveolar fluid and establish-ing the resting lung volume in lungs with sufficient surfactant and may improve initial oxygenation However premature new-borns are obviously physiologically and anatomically less pre-pared for delivery than infants at term Over-inflation has been implicated in histological lung damage in animal models and high tidal volumes appear to be equally damaging whether given before or immediately after administration of surfactant How-ever the same effect is not seen if these excessive tidal volumes are delivered 15 min after administration of surfactant2526 It is now thought that both excess end expiratory volume and inad-equate end-expiratory volume may cause lung damage2728 In premature infants it would therefore seem sensible to use lower pressures of 20ndash25 cmH2O12 delivered in a controlled way to prevent over-inflation and to apply positive end-expiratory pres-sure (PEEP) to prevent damage from under-inflation PEEP also improves both lung compliance and gas exchange2930 Without PEEP the airways collapse during the expiratory phase in animal models of newborn resuscitation
If animal data can be extrapolated it would also seem appro-priate to give surfactant as soon as possible to premature babies in order to ameliorate damage2526
The majority of newborn infants requiring resuscitation will re-establish regular respiration after administration of a few breaths which may be due to Headrsquos paradoxical reflex by which the inflation triggers an inspiratory effort
VentilationOnce the lungs are aerated if the newborn remains apnoeic ventilation should be continued at 30ndash60 breathsmin avoiding hyperventilation and using the minimum pressure possible to maintain a heart rate greater than 100 beatsmin
Face mask the majority of infants who require ventilation receive it via a face mask This may be attached to a bagvalve system with a spring lsquoblow offrsquo system or a lsquoT-piecersquo with a set flow and pressure It is important to realize that the bagvalve system is flow sensitive and that the harder the operator presses the greater the flow and the higher the delivered pressure In fact 60 cmH2O can be achieved with vigorous squeezing of a self-inflating bag Therefore it may be advantageous that most opera-tors are unlikely to be as effective as they suppose in creating a seal with the mask31 This is a skill that requires tuition and prac-tice31 In delivering a set pressure T-piece systems such as the Tom Thumbcopy or Neopuffcopy perform better than any bagminusvalve system but require a gas supply There is no evidence that lung compliance can be assessed using any bag system
Continuous airway pressure case series have suggested that early or delivery room use of continuous positive airway pres-sure (CPAP) in premature babies may reduce chronic lung dis-ease There have been two randomized trials of which one was a pilot study The data from the COIN trial do not show any advan-tage other than a reduction in intubation and surfactant use in the intervention group However an excess of pneumothorax
8 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
was also reported The Vermont Oxford Network and the SUP-PORT trials will provide further data but at present the delivery room use of CPAP cannot be widely recommended and should be limited to those units experienced in its use or taking part in research
Air or oxygen oxygen has been in widespread use for resuscita-tion at birth since the 1930s and even hyperbaric oxygen was seriously supported in the 1960s For many years there have been concerns about tissue damage from oxygen deprivation during and after resuscitation It became evident in the 1950s that unrestricted oxygen therapy could have serious conse-quences for future vision More recently concerns have been raised about potential adverse effects on respiratory physiology cerebral circulation and tissue damage from oxygen free radicals even during resuscitation A meta-analysis of four human studies demonstrated a reduction in mortality and no evidence of harm in infants resuscitated in air versus 100 oxygen3233 However there are several significant methodological concerns with these studies and the results should be interpreted with caution There is insufficient evidence to recommend any specific concentration of oxygen to be used for newborn resuscitation Monitoring the oxygen saturation of babies may be helpful but as yet there are no time-related normal target ranges and healthy term babies may take up to 10 min to achieve preductal oxygen saturation of greater than 95 and up to 60 min to achieve this postductally
There is therefore equipoise which would be open to an appropriate randomized controlled trial In the meantime the evidence only supports use of either 21 or 100 oxygen It is provoking to realize that if air had been in constant use since the 1930s there would be insufficient evidence for use of supple-mental oxygen
Circulation
Early resuscitation (temperature control airway breathing) provides oxygenated blood in the pulmonary arterioles which if returned to the heart causes the rate to increase34 If due to acidosis and hypoxia the circulation is ineffective then chest compressions may be needed They should be commenced when the heart rate remains below 60min despite effective airway and breathing management127 The best technique is using two hands to encircle the chest1 A ratio of three compressions to one breath is internationally accepted127 but has no evidence to support it Research has shown that neither compressions nor drugs will work in this situation without oxygenated blood so effective lung aeration and ventilation is essential A logical approach would be to fill the alveoli with air and to compress the chest until they are empty However training and teamwork require an agreed ratio which has therefore not changed since guidelines were first agreed internationally Success is assessed by an increase in heart rate which should therefore be assessed every 30 s Compressions stop when the spontaneous heart rate is greater than 60 beatsmin
In hypoxic newborn animal models successful resuscitation can restore cardiac output and blood pressure to levels above baseline within 5ndash10 min However it should be noted that there is a decline to 30 lower than basal levels within 2 h and that blood pressure is relatively spared suggesting an even greater
paeDiatRiCS anD CHilD HealtH 184 16
reduction in tissue perfusion This should be considered in the later care of any neonate who was hypoxic at birth
Drugs
Neonatal bradycardia at birth is almost always due to hypoxia plusmn acidosis and therefore drugs are rarely needed Adrenaline (epi-nephrine) is reported as being used in between 1 and 4 babies per 2000 births which is a large variation in practice Reported success is also variable and must be interpreted in light of this variation The use of drugs in extremely premature infants is con-troversial Some data suggested good outcomes for babies below 28 weeksrsquo gestation given adrenaline but these were flawed by high numbers of babies receiving resuscitative drugs some before the airway had been appropriately managed Audit data now suggest a poor outcome such that many clinicians would now council against the use of adrenaline and other drugs to resuscitate extremely premature newborn babies
Adrenaline (epinephrine)In 2003 a Cochrane review of randomized controlled trials involv-ing adrenaline use for resuscitation of neonates was unable to identify a single clinical trial35 Despite the lack of human neo-natal data animal models show the potential of adrenaline in asphyxial cardiac arrest and it is reasonable to use it when ade-quate ventilation and chest compressions have failed to increase the heart rate above 60 beatsmin Use 10ndash30 μgkg intrave-nously and preferably via an umbilical venous line The tracheal route cannot be recommended but if used it is likely that doses within this range will be ineffective and 100 μgkg might be tried However the safety of such doses has not been studied
BicarbonateThe use of bicarbonate has long been controversial but many of the concerns relate to the rapid correction of acidosis in neonates after resuscitation or the routine use of bicarbonate infusion nei-ther of which can be advocated There are no published human neonatal data to support its use although some exist from animal studies Animal data have also shown that the binding of adren-aline to receptors in the myocardium is significantly impaired by lactic acidosis and recent work on human lymphocyte beta-adrenergic receptors supports this view Whether this is also true of the more important alpha receptors is unknown In practice reversing intracardiac acidosis may improve myocardial function and assist in achieving a return of spontaneous circulation 1ndash2 mmolkg of bicarbonate may be given but this remains a contro-versial area
VolumeVolume expansion should only be given when it is suspected that the baby has suffered blood loss or the infant appears to be in shock (pale poor perfusion weak pulse) and has not responded adequately to other resuscitative measures If there is no history suggestive of blood loss shock is most likely to be due to myo-cardial dysfunction in which case fluids should be administered cautiously The most logical replacement fluid would be blood but in its absence isotonic crystalloid rather than albumin is the solution of choice given in 10 mlkg aliquots and observing the response Three randomized trials in neonates have shown
9 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
isotonic crystalloid to be as effective as albumin for the treat-ment of hypotension but none has examined either the relative or actual effectiveness in resuscitation A recent blinded randomized study comparing normal saline albumin or no volume expansion in a normovolaemic asphyxiated neonatal animal model showed that volume expansion was not beneficial and made a number of parameters worse36
NaloxoneNaloxone is not recommended as part of the initial resuscita-tion of newborns with respiratory depression Before it is given supporting ventilation should have restored the heart rate and colour The dose is 100 μgkg intravenously or intramuscularly Tracheal administration cannot be recommended Although administration of naloxone to neonates who have been exposed to maternal opioids during labour is a practice of long-standing it lacks the proper evidence of efficacy
Non-response to resuscitation
There are few more frightening situations professionally than applying the correct interventions in resuscitating or stabilizing a baby and getting no response Each stage must be adequately performed before moving onto the next and this requires regular reassessment When experienced help is needed at a newborn resuscitation it is usually the airway and ventilation that require correction If the heart rate does not increase this usually means that the lungs have not been successfully aerated In some cases however it may mean that the heart cannot respond as the cir-culation is inadequate In this situation the only way to check that the lungs have been successfully aerated is to see the chest move with ventilation or to obtain evidence of ventilation from a detector of exhaled carbon dioxide If you do not see chest movement after another five breaths the most likely cause is an obstructed airway either due to incorrect positioning or because the jaw has not been drawn forwards An oropharyngeal airway can be very helpful at this point especially in the term baby Only very occasionally is the airway blocked by mucus vernix blood or meconium but if the airway is guaranteed and there is no heart rate response or chest movement this should be sought by direct suction of the trachea even in the absence of any meconium staining of liquor Pneumothoraces can occur spontaneously after delivery but are rare at resuscitation carried out with pressure-limited devices Equally rare are diaphragmatic hernias that have not been diagnosed antenatally giving problems at resuscitation
If the chest is moving but the heart rate has not responded to resuscitation consider rare possibilities such as fetal blood loss pneumothorax or heart block (mothers with undiagnosed systemic lupus erythematosis delivered for fetal bradycardia) as possibilities With adequate ventilation there is no evidence of oxygen concentrations less than 100 being responsible for prolonged bradycardia or failure to respond although current practice would support increasing the delivered oxygen concen-tration if resuscitation had been commenced using air
Outcome
The prognosis for the full-term baby subjected to sudden acute asphyxia is usually good provided the episode does not last for
paeDiatRiCS anD CHilD HealtH 184 17
long Most babies resuscitated from primary apnoea have no sequelae secondary to the resuscitation Many babies who start to breathe again regularly within 20 min of the circulation being restored recover completely but it is rare for a baby who is still gasping after 30 min to recover
The prognosis for the preterm baby of less than about 34 weeksrsquo gestation subjected to severe acute anoxia is less predict-able This is because of the risk of secondary intraventricular haemorrhage or periventricular intracerebral haemorrhage andor infarction after even a relatively brief asphyxial episode espe-cially in the period immediately around birth
The effects of chronic hypoxia are also difficult to predict but a reasonably clear idea of the extent of the problem should be obtainable within 36ndash48 h of the original chronic asphyxial insult A mild short-lasting state of hyperexcitability usually car-ries a good prognosis even if there is seizure activity but more severe symptoms can be associated with permanent handicap This is seen especially in infants with encephalopathy requiring ventilation
REFERENCEs
1 Biarent D Bingham R Richmond S et al european Resuscitation
Council guidelines for Resuscitation 2005 Section 6 paediatric life
support Resuscitation 2005 67(suppl 1) S97ndashS133
2 international liaison Committee on Resuscitation part 7 neonatal
resuscitation Resuscitation 2005 67 293ndash303
3 Singh J Santosh S Wyllie J mellon a effects of a course in
neonatal resuscitation - evaluation of an educational intervention
on the standard of neonatal resuscitation Resuscitation 2006 68
385ndash389
4 palme-Kilander C methods of resuscitation in low-apgar-score
newborn infants - a national survey Acta Paediatr 1992 81
739ndash744
5 Kroll l twohey l Daubeney p et al Risk factors at delivery and
the need for skilled resuscitation Eur J Obstet Gynecol Reprod Biol
1994 44 175ndash177
6 Wyllie Jp Resuscitation of the newborn The Foundation Years
2007 3(4) 153ndash157
7 Richmond S ed newborn life Support Resuscitation at Birth
london Resuscitation Council 2006
8 Ceriani Cernadas Jm Carroli g pelligrine l et al the effect of timing
of cord clamping on neonatal venous hematocrit values and clinical
outcome at term a randomized controlled trial Pediatrics 2006
117 e779ndashe786
9 mercer JS Vohr BR mcgrath mm padbury JF Wallach m oh W
Delayed cord clamping in very preterm infants reduces the incidence
of intraventricular hemorrhage and late-onset sepsis a randomized
controlled trial Pediatrics 2006 117 1235ndash1242
10 Dahm lS James lS newborn temperature and calculated heat loss
in the delivery room Pediatrics 1972 49 504ndash513
11 Stephenson J Du J tk o the effect of cooling on blood gas
tensions in newborn infants J Pediatr 1970 76 848ndash852
12 gandy gm adamsons Jr K Cunningham n Silverman Wa James lS
thermal environment and acid-base homeostasis in human infants
during the first few hours of life J Clin Invest 1964 43 751ndash758
13 gluck l Kulovich mV eidelman ai et al Biochemical development
of surface activity in mammalian lung pulmonary lecithin synthesis
0 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
in the human fetus and newborn and etiology of the respiratory
distress syndrome Pediatr Res 1972 6 81ndash99
14 Vohra S Roberts RS Zhang B Janes m Schmidt B Heat loss
prevention (Help) in the delivery room a randomised controlled
trial of polyethylene occlusive skin wrapping in very preterm infants
J Pediatr 2004 145 750ndash753
15 owen CJ Wyllie Jp Determination of heart rate in babies at birth
Resuscitation 2004 60 213ndash217
16 orsquoDonnell Cp Kamlin Co Davis pg Carlin JB morley CJ Clinical
assessment of infant colour at delivery Arch Dis Child Fetal
Neonatal Ed 2007 92 F465ndashF467
17 international liaison Committee on Resuscitation part 13 neonatal
Resuscitation guidelines Circulation 2005 112(suppl 24)
iV188ndashiV195
18 leone ta Rich W Finer nn neonatal intubation Success of
pediatric trainees J Pediatr 2005 146 638ndash641
19 orsquoDonnell Cp Kamlin Co Davis pg morley CJ endotracheal
intubation attempts during neonatal resuscitation success
rates duration and adverse effects Pediatrics 2006 117
e16ndash21
20 Repetto Je Donohue pa-CpK Baker SF Kelly l nogee lm use of
capnography in the delivery room for assessment of endotracheal
tube placement J Perinatol 2001 21 284ndash287
21 gandini D Brimacombe JR neonatal resuscitation with laryngeal
mask airway in normal and low birth weight infants Anesth Analg
1999 89 642ndash643
22 esmail n Saleh m ali a laryngeal mask airway versus endotracheal
intubation for apgar score improvement in neonatal resuscitation
Egypt J Anesthiol 2002 18 115ndash121
23 Wiswell te gannon Cm Jacob J et al Delivery room management
of the apparently vigorous meconium-stained neonate results of
the multicenter international collaborative trial Pediatrics 2000
105 1ndash7
24 Vain ne Szyld eg prudent lm Wisewell te aguilar am Vivas ni
oropharyngeal and nasopharyngeal suctioning of meconium-stained
neonates before delivery of their shoulders multicentre randomised
controlled trial Lancet 2004 364 597ndash602
25 Bjorklund lJ ingimarsson J Curstedt t larsson a Robertson B
Werner o lung recruitment at birth does not improve lung function
in immature lambs receiving surfactant Acta Anaes Scand 2001 45
986ndash993
26 Bjorklund lJ ingimarsson J Curstedt t et al manual ventilation
with a few large breaths at birth compromises the therapeutic effect
of subsequent surfactant replacement in immature lambs Pediatr
Res 1997 42 348ndash355
paeDiatRiCS anD CHilD HealtH 184 17
27 taskar V John J evander e Robertson B Jonson B Surfactant
dysfunction makes lungs vulnerable to repetitive collapse and re-
expansion Am J Respir Crit Care Med 1997 155 313ndash320
28 muscedere Jg mullen JB gan K Slutsky aS tidal ventilation at low
airway pressures can augment lung injury Am J Respir Crit Care Med
1994 149 1327ndash1334
29 nilsson R grossman g Robertson B Bronchiolar epithelial lesions
induced in the premature rabbit neonate by short periods of artificial
ventilation Acta Pathol Microbiol Scand 1980 88 359ndash367
30 probyn me Hooper SB Dargaville pa et al positive end expiratory
pressure during resuscitation of premature lambs rapidly improves
blood gases without adversely affecting arterial pressure Pediatr
Res 2004 56 198ndash204
31 Wood Fe morley CJ Dawson Ja et al improved techniques
reduce face mask leak during simulated neonatal resuscitation
study 2 Arch Dis Child Fetal Neonatal Ed in press doi101136
adc2007117788
32 tan a Schulz a orsquoDonnell CpF Davis pg air versus oxygen for
resuscitation of infants at birth Cochrane Database Syst Rev 2004
(3) CD002273
33 Davis pg tan a orsquoDonnell Cp Schulze a Resuscitation of newborn
infants with 100 oxygen or air a systematic review and meta-
analysis Lancet 2004 364 1329ndash1333
34 Dawes g Fetal and neonatal physiology Chicago year Book
publisher 1968 p 141ndash159
35 Ziino aJa Davies mW Davis pg epinephrine for the resuscitation
of apparently stillborn or extremely bradycardic newborn infants
Cochrane Database Syst Rev 2003 (2) CD003849
36 Wyckoff m garcia D margraf l perlman J laptook a Randomized
trial of volume infusion during resuscitation of asphyxiated neonatal
piglets Pediatr Res 2007 61 415ndash420
Practice points
bull Resuscitation at birth is different from that at all other times
of life
bull a standard approach can be applied to most newborn
resuscitation
bull guidelines are based on a rigorous evaluation of evidence
where possible
bull evidence is sparse but evolving
bull most preterm babies require stabilization rather than
resuscitation
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Acidndashbase physiology and blood gas interpretation in the neonateSusern tan
morag Campbell
Abstractacidndashbase balance describes the complex processes that work to main-
tain a stable extracellular pH for optimal cellular function the process
of balancing the production and neutralization of tissue acid provides a
great challenge for newborn infants who have significantly higher rates
of acid production than adults Factors which help maintain a stable
acidndashbase balance include buffers the respiratory system and renal sys-
tem Both intracellular and extracellular buffers resist changes in pH
the most important extracellular buffer system for maintaining stable
pH is the bicarbonate system in response to acidosis or alkalosis the
respiratory system balances the production of acid with the clearance
of Co2 by altering respiratory rate the kidneys provide a delayed but
sustained response to pH imbalance by excreting either acidic or alkaline
urine in response to systemic acidosis and alkalosis respectively in sick
premature infants these systems have a limited capacity completely to
control pH this review discusses the physiology of the three systems
which control acidndashbase balance patterns of clinical abnormalities in
acidndashbase status and their underlying causes are discussed We present
a systematic approach to blood gas analysis and interpretation in new-
born infants
Keywords acidosis alkalosis bicarbonate bloodndashgas analysis
metabolic pH
Introduction
Blood gas analysis is a routine procedure performed on newborn babies receiving respiratory support in the neonatal intensive care The combination of invasive and non-invasive assessment of ventilation and oxygenation enables clinicians appropriately to modify respiratory care according to each individual babyrsquos rapidly changing clinical status
Understanding the fundamentals of acidndashbase balance helps us to use blood gas analysis not only to assess respiratory sta-tus but also to provide information on metabolic status and the adequacy of tissue perfusion
Susern Tan MBBS MRCP is Clinical Fellow at the Neonatal Intensive Care
Unit 6th Floor North Wing St Thomasrsquo Hospital London SE1 7EH UK
Morag Campbell MBChB MRCP is Consultant Neonatologist at the
Neonatal Intensive Care Unit 6th Floor North Wing St Thomasrsquo
Hospital London SE1 7EH UK
paeDiatRiCS anD CHilD HealtH 184 17
What is understood by acid-base balance
Acidndashbase balance refers to the complex physiological processes used by the body to maintain a stable extracellular pH1 A serum pH within the range of 735ndash745 provides the ideal environment for cellular metabolism Maintaining a stable pH is critical as the metabolic activity of proteins is pH dependent and small changes in hydrogen ion (H+) concentration can potentially alter physio-logical function
Acids are substances that yield free H+ in solution while a base accepts H+ and in solution combines with an acid to neu-tralize it In the normal metabolic state H+ are continuously pro-duced and neutralized to maintain a steady pH balance12 The rate of H+ production is two to three times higher in neonates because of their rapid growth rates and increased acid production from protein turnover and bone mineralization The challenge of maintaining a stable pH through processing and neutralizing H+ is therefore greatest in newborn infants
Using exact values of H+ concentration to assess acidndashbase status is cumbersome and it is more commonly expressed as pH defined by the equation
pH = minuslog H+
Maintaining acidndashbase balance
The balance between production and excretion of acids in the body is controlled by buffer systems which have an immediate effect and by the respiratory and the renal systems
Buffer systemsBuffer solutions resist change in pH when acid or alkali is added due to their capacity to absorb or give up H+ The three main buffer systems in the body are the bicarbonate phosphate and protein systems1ndash3 The protein and phosphate buffer systems are intracellular and act as lsquosinksrsquo for extracellular H+ which are exchanged with intracellular potassium (K+) and sodium ions (Na+) In an acute metabolic acidosis hyperkalaemia may develop due to this H+ exchange4
The bicarbonate buffer system is extracellular and consists of a mixture of carbonic acid (H2CO3) and sodium bicarbon-ate (NaHCO3) This buffer system helps maintain a stable pH by soaking up excess H+ with HCO3
minus which in solution forms carbonic acid (H2CO3) Carbonic acid is a weak acid and readily dissociates to give CO2 which is transported in dissolved form to the lungs for excretion
H+ + HCO3minus harr H2CO3 harr H2O + CO2
The bicarbonate system therefore completes the neutraliza-tion of excess H+ and a stable plasma pH is maintained The relationships between pH HCO3
minus and CO2 in this system are described by the HendersonndashHasselbalch equation15
pH = 61 + log HCO3minus003 times CO2
where 61 is the log of the dissociation coefficient of carbonic acid and 003 the solubility of CO2 in plasma Buffers are most potent when there are equal amounts of H+ and HCO3
minus in solution The
2 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
bicarbonate system is not a potent buffer however as HCO3minus
and CO2 are readily altered by the body this system plays a very powerful role in pH homeostasis15
Respiratory regulationThe respiratory system adapts within minutes to hours as part of the acute response to acidosis This system modifies pH by balancing production of H+ with ventilatory clearance of CO2
H+ directly stimulates chemoreceptors in the respiratory cen-tre of the brainstem producing an increase in respiratory rate26 The response to respiratory acidosis is very rapid as CO2 easily diffuses across the bloodndashbrain barrier however in metabolic acidosis compensation is delayed until plasma bicarbonate fully equilibrates with cerebrospinal fluid (CSF) bicarbonate There is an inverse relationship between alveolar ventilation and partial pressure of dissolved carbon dioxide (PaCO2) a reduction in alveolar ventilation raises PaCO2 and decreases pH Changes in pH therefore affect alveolar ventilation and conversely changes in alveolar ventilation cause significant changes in pH
Renal regulationThe kidneys provide a delayed but sustained response to acidndashbase imbalances by excreting either acidic or alkaline urine In full-term and preterm babies the capacity for acid excretion and bicarbonate reabsorption is reduced as glomerular filtration rates are low and tubular function immature7 Renal function matures with gestation postnatal age and glucocorticoid and thyroid hormones78 Due to their limited capacity to preserve HCO3
minus newborn infants have lower serum bicarbonate levels and are predisposed to acidosis7
Bicarbonate is not effectively reabsorbed due to its size and electrical charge Instead intraluminal HCO3
minus combines with secreted H+ in tubular luminal fluid to produce carbonic acid which dissociates to give H2O and CO2 This CO2 diffuses into tubular cells combines with intracellular H2O and forms carbonic acid which liberates HCO3
minus and H+ HCO3minus is then
recovered to the circulation by exchange for chloride ions (Clminus) through the basal cell membrane247
Renal acid secretion occurs at all sites except the loop of Henle Primary active transport accounts for 5 and secondary for the remaining 95 of total H+ excretion Secondary trans-port involves an exchange between luminal Na+ and intracel-lular H+ Both ions bind to a membrane transport protein The Na+ concentration gradient between the tubular lumen and cells enables Na+ drag into the cell which generates energy to fuel active H+ excretion into the tubular lumen1ndash47
Quantifying acidosis
Standard base excess is a calculated value derived from PaCO2 and pH It is expressed as the mmollitre of base above or below normal buffer bases required to correct the pH to 74 at a PaCO2 of 40 mmHg A negative base excess or base deficit indicates an acidosis while a positive base excess indicates a relative alkalosis15
Anion gap is the measured difference between anions and cations in the blood
Anion gap = (Na+ + k+) minus (HCO3+Clminus)
paeDiatRiCS anD CHilD HealtH 184 17
Calculation of the anion gap enables clinicians better to define the underlying cause of a metabolic acidosis9 The common causes of an increased anion gap acidosis in neonates include lactic acidosis due to tissue hypoperfusion and hypoxia it may also be seen with certain inborn errors of metabolism and in uraemia910 The anion gap can help distinguish between the rela-tively benign non-anion gap hyperchloraemic acidosis seen in premature infants and a pathological lactic acidosis due to poor end-organ perfusion1011
Strong ion theory
Stewart described a complex acidndashbase model which proposed that H+ concentration results from the dissociation of water which is influenced by PaCO2 the strong ion difference and plasma weak acids12
Strong ions are ions that dissociate at normal body pH and include Na+ K+ and Clminus Weak acids in plasma which contrib-ute include albumin inorganic phosphate and plasma proteins their concentrations do not change with pH and are therefore a constant The effect of these factors and other unmeasured tissue ions on acidndashbase status can be quantified by the calculation of the strong ion gap (SIG)112 In the neonatal unit it is perhaps more important that we consider how principles of this model may relate to acidndashbase status rather than fully to quantify the SIG Theoretically low albumin and phosphate levels which fre-quently occur in premature infants by reducing the concentra-tion of weak acids can produce a relative alkalosis while high phosphate levels in renal failure may contribute to acidosis
Tissue oxygenation
Oxygenation is closely linked to acidndashbase status as optimal cel-lular function requires oxygen to fuel aerobic metabolism and produce energy In hypoxic conditions anaerobic metabolism predominates which is energy inefficient and results in a lactic acidosis1011
Tissue oxygen availability is related to regional blood flow haemoglobin level and haemoglobin oxygen affinity Arterial blood gases measure the partial pressure of dissolved oxygen (PaO2) which represents a small component of total oxygen con-tent the majority being transported bound to haemoglobin The relationship between percentage haemoglobin saturation (SaO2) and PaO2 is described by the sigmoidal oxyhaemoglobin disso-ciation curve which enables us to relate the two measures to each other235 The affinity of haemoglobin for oxygen is altered by local tissue factors Increases in temperature H+ PaCO2 and 23-diphosphoglycerate (DPG) levels shift the oxyhaemoglobin dissociation curve to the right reducing affinity for oxygen Decreases in temperature H+ PaCO2 and 23-DPG levels shift the curve to the left increasing oxygen affinity1ndash35 In the body haemoglobin oxygen affinity continuously changes increasing in the lungs to enable efficient oxygen uptake and decreasing at tissue level to provide efficient oxygen delivery to metabolically active tissues
Avoiding both hypoxia and hyperoxia is important in the neo-natal unit as deleterious effects of hypoxia are seen in infants with pulmonary hypertension1314 while hyperoxia is associated with an increased incidence of retinopathy of prematurity1516
3 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Clinical acidndashbase imbalances
Clinical acidndashbase imbalances can be respiratory metabolic or a mixture of both These abnormalities may be corrected by the acidndashbase regulatory mechanisms in the body in an attempt to maintain normal pH (Figure 1)
Respiratory acidosisThis occurs when any disorder leads to decreased alveolar ventilation Common causes of respiratory acidosis are listed in Table 1 Reduced respiratory clearance of CO2 means more dissolved CO2 accumulates in the plasma leading to increased production of carbonic acid and H+ Through chemoreceptor stimulation respiratory acidosis rapidly alters ventilation in an attempt to reduce CO226 Chemoreceptor mediated ventila-tory increases may only partly adjust in premature infants with underlying lung disease In babies with a sustained respiratory acidosis eg in chronic lung disease then metabolic compen-sation occurs through increased renal excretion of H+ and reabsorption of HCO3
minus slowly restoring pH to around 80 of normal47
paeDiatRiCS anD CHilD HealtH 184 17
The management of PaCO2 levels in infants receiving mechan-ical ventilation has important clinical implications Premature babies have impaired cerebral autoregulation17 and adverse neurological sequelae are reported in association with high PaCO2 levels18ndash20 Ventilation strategies which advocate lsquoper-missive hypercarbiarsquo have been developed to minimize airways damage from mechanical ventilation21 Published data suggest pulmonary benefits however the safe level of PaCO2 remains to be defined in premature infants2021
Respiratory alkalosisThis occurs when more CO2 is excreted than is produced by the body Pathological conditions leading to respiratory alkalosis are rare Hyperventilation in the neonatal setting is often iatrogenic or may be due to disorders in brainstem control of breathing including hypoxicndashischaemic encephalopathy or primary central nervous system abnormalities (see Table 1)
If respiratory alkalosis is sustained it may be compensated for by reduced reabsorption of filtered bicarbonate Reported adverse associations of low PaCO2 include periventricular leuco-malacia and intraventricular haemorrhage1922
K+
H+
Overventilation
CO2 + H2O harr H2CO3 harr H+ + HCO3ndash
Bicarbonate Buffer
Intracellular Buffer
uarr H+ excretionuarr HCO3
ndash absorption
uarr buffered H+
(NH4+ H2PO4
ndash)uarr ventilation rate
RespiratoryAcidosis
MetabolicAcidosis
darr CO2and uarr pH
RespiratoryAlkalosis
MetabolicAlkalosis
darr H+ anduarr pH
darr ventilation rate
uarrCO2
and darr pH
darr H+ excretiondarr HCO3
ndash absorption
uarrH+ and
darr pH
Brain
Brain
Intracellular Buffer
H+
K+
Sepsis
HypoxiaRDS
Metabolismand growth
Diuretics
Airwayobstruction
Neuromuscularproblems
IEM
Gastric losses
+ +
ndash -
Renal BufferRespiratory Buffer
Figure 1 mechanisms for regulation of extracellular pH iem inborn errors of metabolism RDS respiratory distress syndrome
4 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Common causes of acidndashbase imbalances
pH PCO2 H2CO3 Base excess Common neonatal causes
Respiratory acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
uarr normal normal bull upper airway obstruction choanal atresia
pierre-Robin sequence
bull lung abnormalities respiratory distress
syndrome transient tachypneoa of
newborn pneumonia meconium aspiration
syndrome pulmonary hypoplasia
congenital pulmonary malformations
bull Central hypoventilation hypoxic-ischaemic
encephalopathy intracranial haemorrhage
bull neuromuscular insufficiency congenital
myopathies congenital neuropathies
bull iatrogenic inadequate ventilatory settings
Compensated lower limit
of normal
uarr uarr gt+3
metabolic acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
normal darr ltminus3 increased anion gap
bull lactic acidosis sepsis hypoperfusion
shock necrotizing enterocolitis
bull inorganic acidosis inborn errors of
metabolism renal failure
normal anion gap
bull increased gastrointestinal H2Co3 losses
ileostomy diarrhoea
bull Renal tubular acidoses
Compensated lower limit
of normal
darr darr ltminus3
Respiratory alkalosis Uncompensated gt 745 darr normal normal bull iatrogenic excessive ventilatory settings
bull Compensatory hyperventilation hypoxic-
ischaemic encephalopathy
Compensated higher limit
of normal
darr darr ltminus3
metabolic alkalosis Uncompensated gt 745 normal uarr gt+3 bull gastric losses vomiting non-replacement
of excessive nasogastric aspirates
bull thiazide and loop diuretics
bull Hypokalaemia
Compensated higher limit
of normal
uarr uarr gt+3
Table 1
Metabolic acidosisThis frequently affects infants in the neonatal unit and has many causes1011 (see Table 1) There may be overproduction of tissue acid impaired acid clearance gastrointestinal loss of bicarbonate or an exogenous increased acid load eg chloride total paren-teral nutrition (TPN) or albumin1ndash323
Calculation of the anion gap to distinguish an increased anion gap acidosis from a non-anion gap acidosis is important both for treatment and prognosis1011 Acidosis stimulates respiratory compensation but this is limited in unstable infants Similarly renal compensation with improved HCO3
minus conservation is con-strained by tubular immaturity Treatment of the acidosis should be directed at the underlying cause eg hypoxia hypotension or excess Clminus rather than by administration of base
Metabolic alkalosisThis is unusual in neonates and is most frequently seen in infants with chronic lung disease or heart failure who are receiving diuretics Diuretics cause alkalosis by increasing renal fluid and Na+ losses An active process to reabsorb Na+ occurs in tubule cells which through enhanced H+ secretion and HCO3
minus reab-sorption produce alkalosis27
paeDiatRiCS anD CHilD HealtH 184 17
Metabolic alkalosis may also occur with excessive loss of gas-tric contents eg protracted vomiting or inadequate replacement of nasogastric aspirates (see Table 1)
Interpreting blood gases
Blood gas measurements can provide important diagnostic and prognostic information and a systematic approach to blood gas analysis is described in Table 2 The clinical management of infants with abnormal gases requires a good understanding of acidndashbase physiology and tissue oxygenation and an apprecia-tion of factors which may affect the reliability of samples
Arterial blood sampling is the gold standard however indwelling arterial catheters and arterial stab samples are usually restricted to infants who are critically ill or those who require sig-nificant ongoing intervention Gases are most frequently measured in capillary or venous samples which correlate well with arterial samples for PaCO2 pH and base excess in babies and children receiving intensive care These correlations however are not valid in infants with peripheral vasoconstriction and hypotension2324
Non-invasive monitoring techniques may enable us to reduce the frequency of blood gas sampling Transcutaneous monitoring
5 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
A systematic approach to blood gas analysis
1 Collect the relevant information
bull type of gas ndash capillary or arterial
bull Current respiratory support ndash document level
bull transcutaneous Co2 and Sao2 levels
bull Clarify no significant clinical events before sampling
2 pH accept a range between 730 and 745 in newborn
babies this is lower than in older children is there an
alkalosis (pH gt 745) or an acidosis (lt 730)
3 Co2 aim for a range between 45 and 65 kpa a paCo2 level
more than 65 kpa suggests inadequate alveolar ventilation
while less than 45 kpa suggests hyperventilation Correlate
values with non-invasive measures
4 o2 Can only be assessed from arterial gases aim for pao2
between 60 and 80 kpa Correlate results with pulse
oximetry levels
5 HCo3 and base excess normal HCo3 level is between 20 and
24 mmollitre and bases excess +3 to minus3
6 anion gap look at the anion gap and lactate to help identify
the cause of an acidosis normal lactate levels should be less
than 2 mmollitre
7 Respiratory or metabolic compensation look at the pH and
assess whether it is appropriate for the Co2 level or is there
evidence of compensation
8 interpret use both the clinical history and blood gas
findings to help you identify the primary problem aim your
management at treating the underlying cause
9 Reassess if clinical management changes have been made
repeat the blood gas after an appropriate time interval to
ensure improvement
Table 2
provides a highly accurate and reliable method for measuring PaCO2 through the skin it can however be technically difficult may cause tissue damage and is of limited reliability when peripheral perfusion is reduced25 Continuous end-tidal CO2 measurements correlate well with arterial CO2 values in patients with normal ventilation and perfusion however in babies with lung disease alveolar collapse small tidal volumes and rapid respiratory rates can make these measurements unreliable26 Despite its limitations transcutaneous monitoring provides the best method for CO2 trend monitoring in the neonatal intensive care unit (NICU)25
Oxygen saturation levels can be continuously measured non-invasively using pulse oximetry While oximetry is easy to perform and accurate on occasion SaO2 levels obtained may be unreliable when tissue perfusion is poor or with movement artefact SaO2 monitoring is highly sensitive at detecting hypoxia but is limited in detecting hyperoxia as at levels more than 90 small changes in SaO2 may result in unacceptably large increases in PaO227 It is therefore essential that SaO2 alarm limits are set for all neonates receiving respiratory support to detect hypoxia and prevent hyperoxia1627
Continuous non-invasive monitoring provides invaluable information when managing complex infants in the NICU but it does not replace the need for regular blood gas analysis
paeDiatRiCS anD CHilD HealtH 184 17
ReFeRenCeS
1 Kellum Ja Determinants of blood pH in health and disease
Crit Care 2000 4 6ndash14
2 Quigley R Baum m neonatal acid base balance and disturbances
Semin Perinatol 2004 28 97ndash102
3 Brouillette Rt Waxman DH evaluation of the newbornrsquos blood gas
status Clin Chem 1997 43 215ndash221
4 Chan JC acid-base disorders and the kidney Adv Pediatr 1983 30
401ndash471
5 Siggaard-andersen o the pH-log pCo2 blood acidndashbase nomogram
revised Scand J Lab Invest 1962 14 598ndash604
6 Saetta m mortola Jp interaction of hypoxic and hypercapnic stimuli
on breathing pattern in the newborn rat J Appl Physiol 1987 62
506ndash512
7 Baum m Quigley R postnatal renal development in Seldin DW
giebisch g eds the kidney physiology and pathophysiology new
york lippincott Williams and Wilkins 2000 p 703ndash726
8 ortiz la Quan a Weinberg a et al effect of prenatal
dexamethasone on rat renal development Kidney Int 2001 59
1663ndash1669
9 gabow pa Kaehny WD Fennessey pV goodman Si gross pa
Schrier RW Diagnostic importance of an increased serum anion gap
N Engl J Med 1980 303 854ndash858
10 lorenz Jm Kleinman li markarian K oliver m Fernandez J Serum
anion gap in the differential diagnosis of metabolic acidosis in
critically ill newborns J Pediatr 1999 135 751ndash755
11 Deshpande Sa platt mp association between blood lactate and
acid-base status and mortality in ventilated babies Arch Dis Child
1997 76 F15ndash20
12 Stewart pa modern quantitative acid-base chemistry Can J Physiol
Pharmacol 1983 61 1444ndash1461
13 Dakshinamurti S pathophysiologic mechanisms of persistent
pulmonary hypertension of the newborn Pediatr Pulmonol 2005
39 492ndash503
14 mourani pm ivy DD gao D abman SH pulmonary vascular
effects of inhaled nitric oxide and oxygen tension in
bronchopulmonary dysplasia Am J Respir Crit Care Med 2004
170 1006ndash1013
15 Deulofeut R Critz a adams-Chapman i Sola a avoiding hyperoxia
in infants le 1250 g is associated with improved short- and long-
term outcomes J Perinatol 2006 26 700ndash705
16 Chow lC Wright KW Sola a Can changes in clinical practice
decrease the incidence of severe retinopathy of prematurity in very
low birth weight infants Pediatrics 2003 111 339ndash345
17 Boylan gB young K panerai RB Rennie Jm evans DH Dynamic
cerebral autoregulation in sick newborn infants Pediatr Res 2000
48 12ndash17
18 Kaiser JR gauss CH pont mm Williams DK Hypercapnia during
the first 3 days of life is associated with severe intraventricular
hemorrhage in very low birth weight infants J Perinatol 2006 26
279ndash285
19 Fabres J Carlo Wa phillips V Howard g ambalavanan n Both
extremes of arterial carbon dioxide pressure and the magnitude of
fluctuations in arterial carbon dioxide pressure are associated with
severe intraventricular hemorrhage in preterm infants Pediatrics
2007 119 299ndash305
20 thome uH Carroll W Wu tJ et al outcome of extremely preterm
infants randomized at birth to different paCo2 targets during the
first seven days of life Biol Neonate 2006 90 218ndash225
6 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
21 Carlo Wa Stark aR Wright ll et al minimal ventilation to prevent
bronchopulmonary dysplasia in extremely-low-birth-weight infants
J Pediatr 2002 141 370ndash374
22 okumura a Hayakawa F Kato t et al Hypocarbia in preterm
infants with periventricular leukomalacia the relation between
hypocarbia and mechanical ventilation Pediatrics 2001 107
469ndash475
23 peters o Ryan S matthew l Cheng K lunn J Randomised
controlled trial of acetate in preterm neonates receiving parenteral
nutrition Arch Dis Child 1997 77 F12ndash15
24 yildizda D yapiciolu H yilmaz Hl Sertdemir y Correlation of
simultaneously obtained capillary venous and arterial blood gases
of patients in a paediatric intensive care unit Arch Dis Child 2004
89 176ndash180
25 aliwalas ll noble l nesbitt K et al agreement of carbon
dioxide levels measured by arterial transcutaneous and end tidal
methods in preterm infants 28 weeks gestation J Perinatol 2005
25 26ndash29
26 Hagerty JJ Kleinman me Zurakowski D et al accuracy of a new
low-flow sidestream capnography technology in newborns a pilot
study J Perinatol 2002 22 219ndash225
paeDiatRiCS anD CHilD HealtH 184 17
27 poets CF Wilken m Seidenberg J Southall Dp von der Hardt H
Reliability of a pulse oximeter in the detection of hyperoxemia
J Pediatr 1993 122 87ndash90
Practice points
bull a stable extracellular pH is important for optimal cellular
functioning
bull abnormalities in acidndashbase balance are regulated by buffer
systems and the respiratory and renal tract
bull maintaining a stable pH is challenging for newborn babies
due to their high rates of acid production and immature
regulatory mechanisms
bull arterial or capillary blood gases provide an effective way to
monitor acidndashbase balance in newborns
bull Blood gases should be analysed in a structured manner
assessing pH and then respiratory and metabolic components
bull the treatment of acidndashbase abnormalities should be directed
at the underlying problem not merely at correcting pH
7 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Recognition and management of neonatal seizuresmalcolm levene
AbstractSeizures are the most common major manifestation of central nervous
system dysfunction in the newborn there are many causes but perina-
tal asphyxia and haemorrhagicinfarction lesions account for about 75
there is now considerable evidence that frequent but short seizures in
the neonate affect subsequent neurodevelopmental outcome Studies
using eeg or modified continuous tracing of eeg activity (aeeg or CFm)
have shown that there is often electroconvulsive dissociation this re-
fers to poor correlation between electrical seizures and clinical seizures
Commonly used anticonvulsants appear to increase electroconvulsive
dissociation effective management of neonatal seizures has proved very
disappointing and less than 50 of seizures are abolished by first-line
anticonvulsant medication (phenobarbitone or phenytoin) Drugs such
as midazolam and lidocaine may further reduce seizures but require
more evaluation the challenge is to assess new and more effective anti-
convulsants which are themselves associated with little neurotoxicity
Keywords antiepileptic drugs eeg neonatal seizures neurodegeneration
Convulsions are the most common major neurological sign seen in newborn infants and their incidence estimated from large population studies is 26 per 1000 live births1 Premature infants are over four times more likely to have convulsions than full-term infants12 Neonatal status epilepticus (continuous seizure activity lasting 30 min or more) diagnosed clinically is rare and accounts for only 5 of infants with seizures1 although this is now recognized more frequently as the result of continuous EEG monitoring3
Neonatal convulsions are described as presenting in a num-ber of different ways and various seizure types can be seen in the same baby over a number of hours The frequencies of the various patterns of seizure activity are given in Table 1 In very premature babies and to a lesser extent in term infants minor movement abnormalities may be difficult to identify as subtle seizures These include lip smacking tongue thrusting mouth-ing pedalling type movements of the lower limbs or swimming movements of the arms Apnoea can be a common manifesta-tion of subtle seizures The signs can be protean and vary from baby to baby or even in the same baby Virtually any stereotypic
Malcolm Levene MD FMedSc FRCPCH FRCH is Professor and Head of
Department of Paediatrics and Child Health at University of Leeds Leeds
and Honorary Neonatologist at Leeds General Infirmary Leeds UK
paeDiatRiCS anD CHilD HealtH 184 178
movement may be a manifestation of a seizure disorder in the newborn
Aetiology
The more carefully the fitting baby is investigated the more likely it is that a cause for the seizures will be found A number of recent papers have described the aetiology of neonatal con-vulsions after extensive investigations14 Tekgul et al4 recently studied a consecutive group of full-term infants with evidence of neonatal convulsions (recognized both clinically and on EEG) and reported their outcome Table 2 summarizes these data as well as risk of moderate or severe disability for each causative factor Perinatal asphyxia is the commonest cause for convul-sions in term infants with haemorrhagic or ischaemic lesions also being common
Overall the prognosis for the group of term babies with con-vulsions was good 72 had a favourable outcome Where asphyxia (hypoxicndashischaemic insult) is the cause of neonatal convulsions the outcome is poor in 50 The prognosis for neonatal convulsions when they were due to arterial or cere-brovenous infarction or intracranial haemorrhage was generally good Individually inborn errors are a very rare cause of neo-natal convulsions but in view of the treatable nature of some of these it is essential that these be considered and investigated appropriately5
Patterns of seizure activity in the newborn
Movement pattern Frequency ()
Clonic 50
tonic 20
Subtle 10ndash35 depending on maturity
myoclonic 5
Table 1
Cause incidence and outcome of neonatal convulsions in term infants14
Aetiological factor Incidence () Poor outcome ()
asphyxia 38ndash40 50
Cerebral arteriovenous
infarction
20 0
intracranial haemorrhage 12ndash20 13
Congenital cerebral anomaly 5ndash10 100
Hypoglycaemiahypocalcaemia 3ndash19
infection 3ndash20
inborn error of metabolism 1
unknown cause 10ndash13 0
Refers to moderate and severe neurodevelopmental abnormalitynumbers too small to make meaningful predictions
Table 2
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Controversies in the clinical management of neonatal seizures
In recent years we have learnt much more about the neurobi-ology of seizures and their effect on the developing brain The neonatal brain is in a neurophysiologically hyperexcitable state compared to the more mature brain and therefore is more prone to seizure activity This is due largely to a relative excess of GABA neuroreceptors GABA receptors are usually inhibitory but in the immature brain they have a paradoxically excitatory effect This changes at about term in primates and with progressive develop-ment they adopt a neuroinhibitory role6
The propensity to seizures in the neonatal brain makes resolv-ing the balance of risks between continuing seizure activity on the one hand against potentially adverse effects of therapy on the other a very important equation Added to this is the problem of accurately diagnosing neonatal seizures and whether commonly used anticonvulsants are successful in controlling them
These conundrums can be posed as a series of challenging questions which are discussed below
Do neonatal convulsions cause brain injuryConvulsions are a sign of neurological compromise and may indi-cate significant underlying structural brain damage or biochemi-cal disturbance which may cause further brain damage in its own right There has been considerable debate about the scale of the disability that convulsions cause the immature brain over and above that due to the underlying cause Most of our knowledge comes from studies in rodents and these have provided some tentative answers to this question
Seizures in the mature brain lead to neuronal necrosis but studies in very young rat pups whose brain development is somewhat similar to full-term infants have shown that a series of five brief seizures on five successive days does not cause struc-tural neuronal damage but does produce morphological changes in hippocampal neurones and worryingly deficits in the rat learning and visual spatial memory function in adolescent and adult life7 A single prolonged neonatal convulsion in similarly immature rats does not produce any functional effects8 Others have shown that following priming of the neonatal rat brain by short seizures as described above a further insult comprising induction of status epilepticus in the same rats at an older age causes neuronal necrosis9 This has been referred to as the lsquotwo hit hypothesisrsquo10
A more specific question is does seizure activity in an already significantly compromised brain cause additional neuropathol-ogy Wirrell et al11 studied a series of immature rat pups with the induction of an hypoxicndashischaemic (asphyxial) insult fol-lowed by either chemically-induced fits or a control sham pro-cedure In the more severely asphyxiated animals the degree of brain damage was increased significantly in those that had the additional burden of induced seizures
In summary these studies show that the immature brain is more resistant to short frequent post-seizure damage than the mature brain but despite resulting in no loss of neuronal numbers the function of the brain is permanently affected in later life In the asphyxiated brain seizures appear to have an additional adverse effect on brain damage Furthermore the immature brain that has been lsquoprimedrsquo by early seizures is more
paeDiatRiCS anD CHilD HealtH 184 179
vulnerable to status epilepticus later in life It would appear from these data that frequent seizures in the human infant should be stopped and this begs the question as to whether currently used anticonvulsants effectively control neonatal seizures
Can we rely on clinical versus EEG diagnosis of neonatal convulsionsTraditionally the diagnosis of neonatal convulsions has been made by observation and description of the frequency of abnor-mal movements EEG has been technically difficult in the hostile electrical activity of a neonatal intensive care environment and considerable expertise is required for analysis of the trace It is usually not practical to undertake traditional EEG recordings at the time the baby shows abnormal movements More recently various technological developments have allowed more direct investigation of neuronal electrical activity by either video-EEG or compressed recording of the amplitude integrated EEG (aEEG or CFM)
Rennie et al3 at Kingrsquos College Hospital London have under-taken extensive evaluation of video-EEG and have found that this technique detects many convulsions not recognized by a single channel aEEG or CFM trace Of 19 infants with evidence of convulsions on EEG only four were recognized on CFM but this may have been due to the observersrsquo lack of experi-ence with this technique In other centres that have developed appropriate expertise aEEG or CFM has proved more sensitive to the detection of seizures Video-EEG studies have also shown that many movements interpreted by experienced clinicians to be seizures are not associated with abnormal cortical activity Conversely many electrical seizures are not associated with abnormal movements This is referred to as electroconvulsive dissociation
In summary clinical observation alone to detect the fitting baby is unreliable in that it may either over-detect seizure activ-ity which is not present on EEG or under-detect clinical seizures in infants with EEG-proven convulsions The decision as to which babies to treat with antiepileptic drugs therefore becomes somewhat arbitrary
Do anticonvulsants stop neonatal seizuresAlthough neonatal seizures are common there are few random-ized controlled trials assessing the benefits of antiepileptic drugs (AEDs) in the treatment of this condition Phenobarbitone is the most widely used first-line AED and in an Australasian study 95 of neonatologists and paediatric neurologists used this drug as first-line management12 The most commonly used loading dosage is 20 mgkg but regimens of up to 40 mgkg have been recommended (Table 3)13 Four trials have evaluated the effect of phenobarbitone in abolishing neonatal seizures Two of these studies used EEG to monitor response to the drug1415 and one compared phenobarbitone with phenytoin15 In the latter study seizures were completely controlled in only 43 of babies and in the group where phenytoin was the first drug used com-plete seizure control was achieved in 45 This study switched babies from their first AED to the other if complete control was not obtained on EEG monitoring after exposure to first-line therapy In babies who had been given phenobarbitone as first-line therapy seizure control was only achieved in 57 after phenytoin was added In those given phenytoin first complete
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Dosage regimens for first- second- and third-line anticonvulsants in the neonatal period
Loading dose Second loading dose if first
unsuccessfulMaintenance dose
phenobarbitone 20 mgkg by slow iv injection 10 mgkg iv 25ndash5 mgkg od
phenytoin 20 mgkg iv over 20 min not recommended
midazolam 150ndash200 μgkg iv infusion 1 μgkgmin iv infusion increasing to 5 μgkgmin
until favourable response
lidocaine 2 mgkg iv over 10 min 6 mgkgh for 6 h iv then 4 mgkgh for 12 h then
2 mgkgh for 12 h
lorazepam 005ndash01 mgkg by slow iv injection
Diazepam 03ndash04 mgkg iv over 3ndash5 min
lidocaine should not be used if the infant has previously been treated with phenytoin
Table 3
seizure control was achieved with the adding of phenobarbitone in 62
Boylan et al14 assessed the efficacy of phenobarbitone (20ndash40 mgkg iv over 20 min) in 14 babies monitored by video-EEG in only four was there complete abolition of seizures and in the other 10 electroconvulsive seizure activity increased whereas clinical evidence of seizures reduced This has been termed elec-troclinical dissociation and anticonvulsant drug use in the new-born appears to increase this feature They also showed that the babies least likely to respond to the first-line AED are those with the most abnormal background EEG
Two studies have evaluated the use of phenobarbitone in babies who had sustained significant asphyxial insult at birth Hall et al13 compared high-dose phenobarbitone (mean 39 mgkg) versus standard dose (27 mgkg) and reported fewer convul-sions and a significant reduction of severe disability or death in the high dose group (RR 030 CI 010ndash093) A recent study from India16 of babies with hypoxicndashischaemic encephalopathy ran-domized 25 babies to phenobarbitone (20 mgkg loading dose) and compared them with 20 control babies Only 2 of 25 (4) in the phenobarbitone group developed convulsions compared with 8 of 20 (40) in the control group (p = 001) Because of the specific enrolment criteria (asphyxial insult) neither of these studies is strictly comparable to the studies by Painter et al15 and Boylan et al14 whose intention was to assess the efficacy of first-line anticonvulsant therapy on convulsions of any cause diagnosed either clinically or by EEG
Other anticonvulsants used as second- and third-line drugs have been subject to few studies in the newborn Midazolam is administered as a bolus followed by continuous infusion A recent study17 has shown that in 10 of 13 neonates given intravenous midazolam for status epilepticus control of electri-cal seizures was achieved within the first hour of treatment having been previously shown to be refractory to phenobarbi-tone treatment Some of these babies required a second bolus infusion of midazolam to obtain control of all electrographic seizures
In some parts of Europe lidocaine is used as a third-line anti-convulsant Malingre et al18 evaluated 20 infants refractory to
paeDiatRiCS anD CHilD HealtH 184 180
both phenobarbitone and midazolam and who were then given lidocaine by continuous infusion Lidocaine was effective in abolishing electroconvulsive seizures diagnosed by aEEG in 76 of the treatment courses studied No babies developed cardiac arrhythmias a previously reported complication of lidocaine in older patients As a result of pharmacokinetic studies the dosage regimen has been modified (see Table 3)
In summary phenobarbitone is effective in seizure control in less than 50 of babies and even when combined with phe-nytoin the efficacy of these drugs together remains poor More worrying is the observation that phenobarbitone tends to reduce clinically evident seizures thereby giving the clinician a false sense of security whilst having little or no effect on the num-bers of electroconvulsive disorders This has been summarized appropriately as lsquoafter all these years we still love what doesnrsquot workrsquo19 Both midazolam and lidocaine infusions appear to be effective in abolishing severe seizures in some infants resistant to phenobarbitone Lidocaine should not be given to babies previ-ously exposed to phenytoin for fear of a synergistic adverse effect on cardiac rhythm
Do antiepileptic drugs cause brain damageA riskndashbenefit analysis is needed to evaluate the efficacy of anticonvulsants in stopping neonatal seizures which is poor with standard anticonvulsants as discussed above against the risk of administering the anticonvulsant drugs themselves Phenobarbitone has been reported to have adverse effects on the developing brain including inhibition of brain growth20 neuronal toxicity21 and adverse behavioural and cognitive effects into adult life when administered to young animals22 Phenytoin shows unpredictable plasma levels and potential cardiotoxicity
Recent studies have shown an effect of AED exposure on the developing brain by causing neurodegeneration23 Phenytoin administration to immature rat pups at doses which produce serum levels similar to those achieved in human neonates was associated with widespread neuronal death as a result of apop-tosis (programmed cell death) Phenobarbitone had a similar effect when a dosage regimen similar to 40 mgkg was used and
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
this effect was maximal in the more immature brain Diazepam and clonazepam also resulted in a similar effect Midazolam and lidocaine were not tested in this study The combination of phenobarbitone or phenytoin with diazepam had a particularly profound effect on neurodegeneration
In summary recent data suggest that the commonly used AEDs for neonatal convulsions may in themselves cause neuro-degeneration due to apoptosis with lasting effects on develop-ment Many babies with neonatal convulsions are treated with at least two AEDs and this may produce more severe adverse effects than the seizures themselves
Practical management of neonatal seizures
Assimilation of these data and formulation of a rational policy is difficult when faced with a fitting neonate on an intensive care unit and pressure on the medical staff to lsquodo somethingrsquo but it is important to accept that sometimes doing nothing is preferable to using potentially dangerous drugs in a situation which does not warrant such intervention Many babies who have normal interseizure neurological clinical findings and whose seizures are relatively brief and infrequent probably do not need anticon-vulsant medication A normal or near-normal background EEG trace should reassure the clinician that anticonvulsants can be withheld
Some causes of neonatal convulsions are treatable such as meningitis hypoglycaemia hypocalcaemia and inborn errors of metabolism and each baby should be rapidly and carefully investigated for cause of the convulsions
In some babies clinical assessment of seizures is difficult ie when the baby is very sick small or paralyzed Sometimes it may be difficult to assess the significance of certain movement pat-terns Under these circumstances an EEG may prove to be very helpful In many units EEG is not available out of hours and a simple aEEG or CFM is strongly advised Modern instruments are very simple to apply and prolonged or frequent seizures should be identified with only moderate training The printout can be faxed to a more senior doctor if there is doubt as to what is shown on the trace
The balance of knowledge now is that frequent seizures cause additional damage to the developing brain and that treatment to abolish the seizures is warranted Unfortunately there is little evidence that the majority of seizures can be effectively termi-nated by current standard therapy Furthermore it appears that the more abnormal the background EEG the more difficult it is to control the seizures Nevertheless a written protocol for the management of neonatal convulsions is required on each unit Phenobarbitone and phenytoin remain the mainstay of treat-ment although their effectiveness is disappointing There is little to suggest that midazolam is more effective than lidocaine as third-line therapy but lidocaine is precluded if phenytoin has been previously used
In view of the anxiety as to the neurodegenerative effects on the immature brain of most anticonvulsants used in the neonatal period (particularly when multiple drugs are used) it is prefer-able to use only one drug to maximum dosage before introduc-ing a second In addition the duration of anticonvulsants should be minimized and the drugs stopped at the earliest opportu-nity It is my practice to stop anticonvulsants prior to discharge
paeDiatRiCS anD CHilD HealtH 184 18
from hospital if the baby is neurologically normal on clinical examination
REFEREnCES
1 Ronen gm penney S andrews W the epidemiology of clinical
neonatal seizures in newfoundland a population-based study
J Pediatr 1999 134 71ndash75
2 lanska mJ lanska DJ Baumann RJ et al a population-based study
of neonatal seizures in Fayette County Kentucky Neurology 1995
45 724ndash732
3 Rennie Jm Chorley g Boylan gB et al non-expert use of the
cerebral function monitor for neonatal seizure detection Arch Dis
Child Fetal Neonatal Ed 2004 89 F37ndashF40
4 tekgul H gauvreau K Soul J et al the current etoliologic profile
and neurodevelopmental outcome of seizures in term newborn
infants Pediatrics 2006 117 1270ndash1280
5 Surtees R Wolf n treatable neonatal epilepsy Arch Dis Child 2007
92 659ndash661
6 Ben-ari y Holmes gl effects of seizures on developmental
processes in the immature brain Lancet Neurol 2006 5 1055ndash
1063
7 Holmes gl gairsa Jl Chevassus-au-louis n et al Consequences of
neonatal seizures in the rat morphological and behavioral effects
Ann Neurol 1998 44 845ndash857
8 Stafstrom Ce Chronopoulos a thurber S et al age-dependent
cognitive and behavioural deficits following kainic-acid inducing
seizures Epilepsia 1993 34 420ndash432
9 Schmid R tandon p Stafstrom Ce et al effects of neonatal seizures
on subsequent seizure-induced brain injury Neurology 1999 53
1754ndash1761
10 Hoffmann aF Zhao Q Holmes gl Cognitive impairment following
status epilepticus and recurrent seizures during early development
support for the ldquotwo-hit hypothesisrdquo Epilepsy Behav 2004 5
873ndash877
11 Wirrell eC armstrong ea osman lD et al prolonged seizures
exacerbate perinatal hypoxic-ischemic brain damage Pediatr Res
2001 50 445ndash454
12 Carmo KB Barr p Drug treatment of neonatal seizures by
neonatologists and paediatric neurologists J Paediatr Child Health
2005 41 313ndash316
13 Hall Rt Hall FK Daily DK High-dose phenobarbital therapy in term
newborn infants with severe perinatal asphyxia a randomized
prospective study with three-year follow-up J Pediatr 1998 132
345ndash348
14 Boylan gB Rennie Jm pressler Rm et al phenobarbitone neonatal
seizures and video-eeg Arch Dis Child Fetal Neonatal Ed 2002 86
F165ndash170
15 painter mJ Scher mS Stein aD et al phenobarbital compared with
phenytoin for the treatment of neonatal seizures N Engl J Med
1999 341 485ndash489
16 Singh D Kumar p narang a a randomized controlled trial of
phenobarbital in neonates with hypoxic ischemic encephalopathy
J Matern Fetal Neonatal Med 2005 18 391ndash395
17 Castro Conde JR Borges H Domenech martinez e et al midazolam
in neonatal seizures with no response to phenobarbital Neurology
2005 64 876ndash879
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
18 malingre mm Van Rooij lgm Rademaker Cma et al Development
of an optimal lidocaine infusion strategy for neonatal seizures Eur
J Pediatr 2006 165 598ndash604
19 Sankar R painter mJ neonatal seizures after all these years we still
love what doesnrsquot work Neurology 2005 64 776ndash777
20 Diaz J Schain J Bailey Bg phenobarbital-induced brain growth
retardation in artificially reared rat pups Biol Neonate 1977 32 77ndash82
21 mattson RH phenobarbital toxicity in levy RH Dreifuss Fe
mattson RH et al eds antiepipeptic Drugs 3rd edn new york
Raven 1985 p 341ndash355
22 mikati ma Holmes gl Chronopoulos a et al phenobarbital
modifies seizure-related brain injury in the developing brain Ann
Neurol 1994 36 425ndash453
23 Bittigau p Sifringer m genz K et al antiepileptic drugs and
apoptotic neurodegeneration in the developing brain Proc Natl
Acad Sci U S A 2002 99 15089ndash15094
paeDiatRiCS anD CHilD HealtH 184 182
Practice points
bull the clinician needs to be aware that almost any repetitive
stereotype movement pattern can be a manifestation of
neonatal seizures
bull eeg is important in defining neonatal seizures
bull Frequent short-lived seizures have been shown to cause long-
term neurodevelopmental problems
bull Conventional anticonvulsant medication is ineffective in
abolishing neonatal seizures in greater than 50 of cases
bull there is evidence that exposure of the neonatal brain to
multiple anticonvulsants causes neuronal death
bull Future research is needed to evaluate more effective
anticonvulsants for treating this condition
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
Emotional support for families of sick neonatesMarina nicolaou
cristine Glazebrook
AbstractParents of sick neonates experience high levels of stress anxiety and
depression Most interventions with families of sick infants have focused
on fostering the motherndashinfant relationship through the provision of
information about infant developmental needs or through increased
motherndashinfant contact Many of these studies have reported improved
maternal well-being though there are some concerns about the scope
and practicality of large-scale interventions The few studies to have
prioritized emotional support for parents of sick neonates have pro-
duced encouraging results even interventions requiring relatively few re-
sources such as telephone support parent-to-parent support and group
support have been associated with reduced psychological morbidity for
parents The needs of parents can change throughout their infantrsquos hos-
pitalization and not all want or benefit from the provision of additional
support Thus neonatal intensive care units should aim to provide a
varied flexible and sustainable programme of support options Further
research should focus on the needs of fathers
Keywords mental health neonatal intensive care parents
The admission of an infant to neonatal care is acknowledged to be a source of considerable distress for families This review aims to explore evidence for the psychological impact on families of having an infant in neonatal intensive care and to identify evi-dence for the effectiveness of interventions to promote parental well-being It will conclude with recommendations for strategies to support parents of vulnerable infants and suggestions for fur-ther research
Psychological impact of neonatal care for parents
The majority of research examining the effect on parents of having a sick neonate has focused on families of premature or low birthweight infants Such research has found that parents with a sick neonate exhibit high levels of stress compared to normative samples and to parents of healthy full-term infants1 Singer et al2 examined the stress experienced by mothers of high-risk very low birthweight (VLBW) low-risk VLBW and term
Marina Nicolaou MPhil is a Teaching Assistant at the School of
Community Health Sciences University of Nottingham Nottingham UK
Cristine Glazebrook PhD is a Professor of Health Psychology at the School
of Community Health Sciences University of Nottingham Nottingham UK
PaeDiaTrics anD cHilD HealTH 184 196
infants Several self-report measures were used including the Brief Symptom Inventory the Parenting Stress Index (PSI) the Impact on Family Scale and the Family Inventory of Life Events and Changes (FILE) Mothers of VLBW infants had more psycho-logical distress at 1 month compared to mothers of term infants Mothers of high-risk VLBW infants also reported high psycho-logical distress at 2 years and high levels of parenting stress at 3 years Mothers have also been found to have higher stress levels compared to fathers Shaw et al3 examined the prevalence of acute stress disorder (ASD) in 40 parents whose infants were in the neonatal intensive care unit (NICU) Nearly half of the moth-ers (44) met the criteria for ASD although none of the fathers did Furthermore the severity of the symptoms (measured by the number of concurrent symptoms) was greater for the moth-ers than for the fathers3 The reasons behind this difference have been widely speculated with some believing that it is due to the mothersrsquo greater psychological involvement with the infant as evidenced by their general greater vulnerability to postpartum psychological disorder It could also reflect gender differences in coping style
Having an infant who requires intensive medical care repre-sents a significant emotional burden for families Not only is there extreme anxiety surrounding the infantrsquos health and distress for the childrsquos suffering there is also the unfamiliar and intimidating environment of the NICU to adjust to Hopper in her review of the literature identified sources of stress for parents of sick neo-nates as falling into three areas4 Situational factors included the severity of the infantrsquos illness and how parents adapted to the life crisis of having a sick infant Personal factors involved parental emotions about their roles and the instrumental and informa-tional support which were available to them The third area was classified as environmental sources of stress and included the environment of the NICU and the relationship between parents and members of staff This relationship has been examined by several studies in the nursing literature nurses are seen as ide-ally placed to provide the necessary support and information to parents with sick neonates However whilst some studies have shown that supportive and helpful hospital staff can have a posi-tive effect on parents other studies have highlighted the prob-lems and difficulties which can manifest It has been shown that parents and nurses often have very different ideas about issues eg the necessary skills and competencies needed in an NICU or the characteristics that make a lsquogood motherrsquo
Research has shown that there may be a relationship between high levels of parental stress and an increased likelihood of depression5 Postpartum depression is a psychiatric illness which appears in 10ndash15 of postpartum women Its reported preva-lence rates however have ranged from less than 10 up to 306 depending on the instruments used the population exam-ined and the timing of the research Several factors have been found to be associated with postpartum depression including poor social support and infant-related stressors6 Evidence indi-cates that postnatal depression may be underreported and this is of concern since the mental and psychological health of the mother can affect her relationship with her infant and thus the infantrsquos cognitive and emotional development5 Depressed moth-ers appear to look touch and talk to their infants less frequently and also appear to show fewer positive and more negative faces7 The vocalizations of mothers suffering with depression have also
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
been found to be less effective at promoting cognitive growth and learning in infants8
If researchers are interested in finding ways of providing sup-port for families of sick neonates then they must listen to what such families perceive their needs to be in order to avoid increas-ing anxiety and distress Furthermore the provision of appropri-ate support be it emotional informational or social will enhance parental coping abilities increase self-esteem and reduce anxiety It should be noted though that the research conducted around these issues has often taken lsquosupport needsrsquo as being synony-mous with lsquoinformation needsrsquo Such studies have examined the type the amount and quality of information that parents receive and perceive themselves as needing but have not explored in equal depth the perceived emotional support needs of families who have a sick infant In addition the needs of parents may change throughout their infantrsquos illness Ward examined the per-ceived needs of 52 parents of infants in an NICU9 Parents rated the needs of their hospitalized infant as most important along with the need to be reassured Interestingly they ranked their support needs as least important This research was conducted during the first week of the infantsrsquo hospitalization however which would explain the preoccupation of the parents with the infantrsquos health These results demonstrate that if researchers want to find ways of providing emotional support to parents of sick neonates they must be prepared not only to listen to parents but also to be flexible enough to satisfy the parentsrsquo changing needs and expectations
Interventions aimed at supporting parents
Most interventions that been evaluated in controlled studies have focused on supporting the motherndashinfant relationship and provid-ing information on infant development Many of these interven-tions have included the aim of improving the parental emotional state and thus psychological outcomes such as stress or anxi-ety have been assessed However few studies appear to include fathers This means that strategies implemented to provide emo-tional support to families of sick neonates are often derived from interventions tailored for mothers even though fathers may have different emotional needs
A wide range of interventions with mothers and infants has been evaluated in the NICU Increasing motherndashinfant contact through kangaroo care has been found to reduce maternal anxiety1011 and educational programmes delivered to fami-lies in the NICU have also been associated with reduced emo-tional difficulties in parents12ndash14 Kaaresen and colleagues implemented an intervention which consisted of eight sessions before discharge and four home visits all by trained nurses The sample included 71 premature infants in the intervention group 69 premature infants in the control group and 74 infants in the full-term control group The randomized controlled trial found that the intervention reduced parenting stress in both mothers and fathers of premature infants compared to controls to a level equivalent to parents in the term control group13 At 6 months corrected age mothers of preterm infants who had not received the intervention had total PSI scores which were 17 points higher than the mothers of infants born at term (an effect size of 057) A similar study evaluated the efficacy of an educationalndashbehavioural programmendashCreating Opportunities for
PaeDiaTrics anD cHilD HealTH 184 19
Parent Empowerment (COPE) ndash through a randomized controlled trial with 260 families of premature infants14 COPE was a four-phase educationalndashbehavioural programme which began as early as 2ndash4 d after mothers had given birth and continued until 1 week after discharge from the NICU The programme consisted of audiotaped and written infant behaviour information along with photographs which focused on common behaviours and characteristics of premature infants It also included various par-ent activities in the form of a four-phase workbook which aimed to assist mothers in the implementation of the experimental infor-mation COPE was found significantly to reduce maternal stress in the NICU as well as maternal anxiety and depressive symptoms after hospitalization In contrast a cluster randomized trial of a parenting intervention delivered to mothers of very premature infants from soon after birth showed no benefits for parenting stress1 The authors hypothesized that the intervention had not been of sufficient intensity particularly in the weeks surrounding discharge Neonatal care presents a significant barrier to parent-ing in the early weeks following a very preterm birth and so inter-ventions which focus on the developmental needs of infants and the parentndashchild relationship should particularly aim to support parents as they take on the parenting role There was also concern that the intervention had failed to reach those most at risk
Since large-scale projects can be costly to implement and may often fail to reach the families in most need it may be wiser to focus on intervention programmes which are more practical and easier to implement within a neonatal care setting Research has shown that even interventions which are based on one-off meet-ings with parents of sick neonates can be effective Jotzo and Poets examined the effect of an intervention programme aimed at reducing the severity of traumatic responses as a result of giv-ing birth prematurely15 Their programme consisted of a one-off intervention meeting along with additional psychological help throughout the hospitalization of the infant The meeting cov-ered a variety of issues including a reconstruction of the events shortly before and after the infantrsquos birth relaxation techniques discussion of coping strategies available resources and social support and support during emotional outbursts The measures used included the Impact of Event Scale (IES) and the Peritrau-matic Dissociative Experience Questionnaire At discharge the mothers who received the intervention were found to have a significantly lower traumatic impact as a result of premature birth Furthermore fewer mothers in the intervention group showed symptoms of clinically significant psychological trauma at discharge compared to mothers in the control group (36 vs 76)15 The lsquoParents Circle Programrsquo is another intervention with a similar structure16 This consisted of a 90 min session for parents with the aim of enhancing the developing relationship between parents and infants and to offer parents support A total of 104 parents (59 mothers and 45 fathers) and 44 members of hospital staff were asked to evaluate the programme and their results were analysed using content analysis Families reported gaining perspective on their situation feeling supported becom-ing aware of cues and optimizing interactions and becoming aware of available resources Parents and staff alike felt that participating in the intervention helped parents overcome the difficulties associated with the early time of their infantrsquos hos-pitalization Additional studies have also found positive results with fairly minimal interventions including discussion groups
7 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
in the NICU music during kangaroo care and pairing mothers of sick neonates with trained mothers who had been through similar experiences
Parent support programmes
Parent support programmes (PSPs) which are based in NICUs can provide parents with the opportunity to talk to parents who have been in similar situations and also to discuss their emo-tions with professionals who can help them cope with their situa-tion111718 The parent-to-parent support programme for mothers of preterm infants evaluated by Preyde and Ardal included edu-cational parental support group meetings and individual par-ent-to-parent support (primarily telephone support)19 Measures used included the Parental Stressor Scale NICU the State and the Trait Anxiety Inventories and the Beck Depression Inven-tory After 4 months of participation mothers in the intervention group reported lower levels of stress state anxiety and depres-sion compared to control group mothers The authors speculated however that the participants who were able to meet face to face with other parents were those who benefited the most Hurst conducted a comprehensive survey of an NICU-based PSP This PSP was provided in a variety of formats including a weekly parent support group hospital visitation and 24-h telephone sup-port20 Of the 477 participants 303 families used the PSP dur-ing a 2-year evaluation period with 78 using only one form of support and 18 using two forms Of a sub-sample of 48 parents asked to complete an evaluation of the PSP 92 stated that they would recommend such a programme to other parents Furthermore the majority of parents felt that it made them feel supported and helped them deal with their emotions20 This is an indication that such programmes can be very successful in sup-porting parents throughout their infantrsquos hospitalization It also shows that it can be beneficial to give parents several options and formats when it comes to such support services It is impor-tant to consider though that both the Hurst and the Preyde and Ardal studies found that some participants did not find the sup-port programmes helpful even reporting that they had caused them increased stress and anxiety Therefore it should not be assumed that support programmes will suit every individual and will provide the required support for all parents1920 NICUs need to be flexible enough to provide parents with a range of forms of support to choose from
The increased understanding of the strains that parents of sick neonates have to deal with has also led to efforts to improve customary practices in NICUs Family-centred care focuses on infants and their needs and attempts to redefine the relationship between parents and caregivers These practices strive to provide parents with support during their infantrsquos illness by focusing on freely sharing information and on the collaboration between parents and hospital staff Family-centred care has been found to be associated with several beneficial outcomes including improved parental satisfaction increased parental comfort staff satisfaction and decreased parental stress18 Research is already examining these practices and questioning how these can be improved further Such research reflects the increasing effort focused on lsquohumanizingrsquo the environment in NICUs in order to make parents feel more comfortable about spending time with their infants
PaeDiaTrics anD cHilD HealTH 184 19
Conclusion
Surprisingly few interventions have prioritized the provision of emotional support for parents of sick neonates or accounted for the changing needs and wishes of parents over the course of their infantrsquos care Large-scale supportive education-based inter-ventions have been shown to be effective in reducing parental distress However the feasibility and sustainability of such pro-grammes should also be considered Programmes which require significant additional resources can be expensive and there are also issues of training and quality control Interventions which require significant input from parents may also place additional burdens on families making them potentially less accessible to those most at risk Arguably the aim should be to explore ways of providing acceptable and effective informational support which could be complemented by emotional support from health professionals and from other parents in the unit Increasingly studies are exploring the use of computers and multimedia as an engaging flexible and cost-effective method of targeting indi-vidual needs and providing support and information Such com-puter-based and interactive multimedia interventions have been found to be successful with a range of patient groups and could therefore be examined as a complementary method of providing informational support to families with sick neonates
REfEREnCEs
1 Glazebrook c Marlow n israel c et al randomised trial of a
parenting intervention during neonatal intensive care Arch Dis Child
Fetal Neonatal Ed 2007 92 F438ndash443
2 singer lT salvator a Guo s collin M lilien l Baley J Maternal
psychological distress and parenting stress after the birth of a very
low-birth-weight infant JAMA 1999 281 799ndash805
3 shaw rJ Deblois T ikuta l Ginzburg K Fleisher B Koopman c
acute stress disorder among parents of infants in the neonatal
intensive care nursery Psychosomatics 2006 47 206ndash212
4 Hopper a sources of stress for parents of a sick neonate a
literature review Pediatr Nurs 2000 30 29ndash32
5 Davis l edwards H Mohay H wollin J The impact of very
premature birth on the psychological health of mothers Early Hum
Dev 2003 73 61ndash70
6 Bernazzani O saucier J-F David H Borgeat F Psychosocial
predictors of depressive symptomatology level in postpartum
women J Affect Disord 1997 46 39ndash49
7 Field T infants of depressed mothers Infant Behav Dev 1995 18
1ndash13
8 Kaplan Ps Bachorowski J-a Zarlengo-strouse P child-directed
speech produced by mothers with symptoms of depression fails
to promote associative learning in 4-month-old infants Child Dev
1999 70 560ndash570
9 ward K Perceived needs of parents of critically ill infants in
a neonatal intensive care unit (nicU) Pediatr Nurs 2001 27
281ndash286
10 lai Hl chen cJ Peng Tc et al randomized controlled trial of music
during kangaroo care on maternal state anxiety and preterm infantsrsquo
responses Int J Nurs Stud 2006 43 139ndash146
8 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
11 Tallandini Ma scalembra c Kangaroo mother care and mother-
premature infant dyadic interaction Infant Ment Health J 2006 27
251ndash275
12 Ohgi s Fukuda M akiyama T Gima H effect of an early intervention
programme on low birthweight infants with cerebral injuries
J Paediatr Child Health 2004 40 689ndash695
13 Kaaresen Pi ronning Ja Ulvund se Dahl lB a randomized
controlled trial of the effectiveness of an early-intervention program
in reducing parenting stress after preterm birth Pediatrics 2006
118 e9ndash19
14 Melnyk BM Feinstein nF alpert-Gillis l et al reducing premature
infantsrsquo length of stay and improving parentsrsquo mental health
outcomes with the creating opportunities for parent empowerment
(cOPe) neonatal intensive care unit program a randomized
controlled trial Pediatrics 2006 118 e1414ndash1427
15 Jotzo M Poets cF Helping parents cope with the trauma of
premature birth an evaluation of a trauma-preventive psychological
intervention Pediatrics 2005 115 915ndash919
16 Pearson J andersen K evaluation of a program to promote positive
parenting in the neonatal intensive care unit Neonatal Netw 2001
20 43ndash48
17 roman l lindsay J Boger r et al Parent-to-parent support
initiated in the neonatal intensive care unit Res Nurs Health 1995
18 385ndash394
18 Meyer ec coll cTG lester BM Boukydis cFZ McDonough sM Oh w
Family-based intervention improves maternal psychological well-
being and feeding interaction of preterm infants Pediatrics 1994
93 241ndash246
PaeDiaTrics anD cHilD HealTH 184 19
19 Preyde M ardal F effectiveness of a parent ldquobuddyrdquo program for
mothers of very preterm infants in a neonatal intensive care unit
CMAJ 2003 168 969ndash973
20 Hurst i One size does not fit all Parentsrsquo evaluations of a support
program in a newborn intensive care nursery J Perinat Neonatal
Nurs 2006 20 252ndash261
Practice points
bull Parents of sick neonates experience significant distress and
exhibit higher levels of stress anxiety and depression than
parents of healthy infants
bull educational support emotional support and increased
motherndashinfant contact have been shown to promote maternal
well-being
bull emotional support for fathers has been largely neglected in
the research literature
bull Parents benefit from a choice of supportive facilities which
could include face-to-face sessions with health professionals
telephone support hospital visitation parent-to-parent
support and unit-based group support meetings
bull Parentsrsquo support needs can change during their infantrsquos
hospitalization and not all parents want or benefit from the
provision of additional information and emotional support in
the neonatal unit
9 copy 2008 elsevier ltd all rights reserved
Personal Practice
When should enteral feeds be started in preterm infantsnicholas D embleton
AbstractPaediatricians are regularly faced with the question of when best to start
enteral feeds in preterm infants this is important as longer term out-
come may be compromised by sub-optimal nutrition in early life clinical
factors that may affect the decision to start and the risk and benefits
are discussed
Keywords breast milk feeding nutrition parenteral nutrition
Key points in the history
Alice is lsquonutritionally vulnerablersquo and whilst this may not be immediately apparent it will affect her long term outcome Her energy stores are extremely limited and consist primarily of pro-tein She has less than 5 fat and little energy associated with stored glycogen She is losing about 1 gkgd protein equivalent so she needs at least that and a minimum of 50ndash60 kcalkg of energy just to maintain the status quo let alone grow
Her weight is on the 25th centile Review of any antenatal his-tory may reveal whether fetal growth was normal Fetal growth retardation can occur with a weight greater than 10th centile The presence of antenatal absent or reversed end diastolic flow in the umbilical artery indicates poor gut blood flow This increases the risk of necrotizing enterocolitis (NEC) and might suggest a more cautious approach to starting feeds1
She has no important cardiovascular problems but if she were hypotensive gut blood flow may be low There is no umbilical
Nicholas D Embleton BSC (Hons) MBBS (Hons) MD FRCPCH is Consultant in
Neonatal Medicine at Newcastle Neonatal Service Royal Victoria
Infirmary Newcastle upon Tyne NE1 4LP UK
Should you start feeds at a day of age
alice was born following spontaneous labour at 30 weeksrsquo
gestation she weighed 1300 g and is now 18 h old she was
briefly ventilated and then extubated to continuous positive
airway pressure 12 h ago in 35 oxygen she has had caffeine
citrate but still has intermittent episodes of self-correcting
apnoea she was commenced on iv 10 dextrose but this was
replaced by a parenteral amino acid solution (referred to as
lsquotPnrsquo) along with intralipid at 0900 this morning serum glucose
is 11 mmoll and blood pressure is 42 systolic
PaeDiatrics anD cHilD HealtH 184 20
arterial catheter in situ but there is no good evidence that this should delay the decision to start feeds Her glucose is high but this is quite common in a baby like this Could this be a sign of sepsis Caffeine does not affect the incidence of NEC2 The great-est risk factor for NEC in this case is prematurity
What else might be found on examination
Up until 24 h ago she was swallowing large amounts of amniotic fluid What will have changed since then
General examination should confirm peripheral perfusion lsquogestaltrsquo view (does she look lsquowellrsquo) and cardiovascular status lsquoBowel soundsrsquo are not usually helpful
The most important variable likely to affect gut perfusion is the arterial duct Precordial lsquoheaversquo and a loud murmur are sug-gestive but it is possible to have a significant ductal shunt in a baby with a normal examination Cardiac ultrasound will con-firm this diagnosis It might be better to treat a large shunt first with indometacin and to delay starting feeds for a further 24 h
It is not possible to assess gut perfusion clinically but normal perfusion elsewhere (adequate urine output usually indicates adequate renal perfusion) would be reassuring Most preterm babies have a few abdominal lsquoloopsrsquo visible but a distended abdomen with many palpable loops suggests ileus This might be secondary to sepsis or poor gut blood flow Preterm babies do not pass much meconium in the first 24ndash48 h
Balance of risks between starting and withholding feeds
Alice requires 35ndash4 gkgd of protein and 120 kcalkgd to grow3 This will initially be provided parenterally Delaying feeds increases the risk of gut villous atrophy and prolongs the need for lsquototal parenteral nutrition (TPN)rsquo TPN requires intravenous access and so increases the risk of sepsis and when prolonged use is required combined with the lack of enteral feeding may result in hepatic impairment
Delaying feeds may allow a gut that has been chronically under-perfused to re-establish more normal perfusion although normal gut endocrine function digestive enzyme upregulation and motility require a source of intraluminal nutrients1 A recent study suggested benefit from delaying the introduction of feeds4 but methodologi-cal problems exist5 Although a Cochrane meta-analysis suggested no benefit only two studies were included6 A large UK-based trial is examining the effect of early or late feeding in preterm infants who were born growth retarded following identification of antena-tal absent or reversed end diastolic flow in the umbilical artery7
When starting feeds what volume should be used
There are no good data to guide this decision We start with 24 mlkg (1 mlkgh) and then increase by this amount each day Most babies achieve full enteral feeds (ge150 mlkgd) by a week of age Feeding guidelines improve the outcome8 Measure-ment or assessment of gastric aspirates is not consistently useful in predicting subsequent feeding intolerance or development of NEC Aspirate volumes equivalent to or sometimes greater than the amount given in the preceding 1ndash2 h are usually normal Most aspirates have a greenish colour Thick bloody or intensely bile-stained aspirates require detailed assessment
0 copy 2008 elsevier ltd all rights reserved
Personal Practice
What else affects decisions and outcome
Feeding success is affected by sepsis and NEC Scrupulous atten-tion should be paid to hand washing and intravenous access and blood sampling should be minimized There is no good evidence to support the routine use of pro-kinetic agents or H2 blockers
The most important clinical intervention affecting the occur-rence of NEC is the use of breast milk9 All efforts should be directed at persuading parents of the benefits and supporting the process Some clinicians delay starting feeds for a further 24 h whilst expressed breast milk becomes available Donor breast milk might be equally efficacious10
RefeRenceS
1 Dorling J Kempley s leaf a Feeding growth restricted preterm
infants with abnormal antenatal Doppler results Arch Dis Child Fetal
Neonatal Ed 2005 90 F359ndash363
2 schmidt B roberts rs Davis P et al caffeine therapy for apnea of
prematurity N Engl J Med 2006 354 2112ndash2121
PaeDiatrics anD cHilD HealtH 184 20
3 embleton nD Pang n cooke rJ Postnatal malnutrition and growth
retardation an inevitable consequence of current recommendations
in preterm infants Pediatrics 2001 107 270ndash273
4 Berseth cl Bisquera Ja Paje VU Prolonging small feeding volumes
early in life decreases the incidence of necrotizing enterocolitis in
very low birth weight infants Pediatrics 2003 111 529ndash534
5 Menon G Boyle eM embleton nD et al introduction of enteral
feeds in preterm infants Pediatrics 2004 114 327ndash328
6 Kennedy Ka tyson Je chamnanvanikij s early versus delayed
initiation of progressive enteral feedings for parenterally fed low
birth weight or preterm infants Cochrane Database Syst Rev 2000
cD001970
7 wwwnpeuoxacukadept
8 Patole sK de Klerk n impact of standardised feeding regimens on
incidence of neonatal necrotising enterocolitis a systematic review
and meta-analysis of observational studies Arch Dis Child Fetal
Neonatal Ed 2005 90 F147ndash151
9 lucas a cole tJ Breast milk and neonatal necrotising enterocolitis
Lancet 1990 336 1519ndash1523
10 Boyd ca Quigley Ma Brocklehurst P Donor breast milk versus
infant formula for preterm infants systematic review and meta-
analysis Arch Dis Child Fetal Neonatal Ed 2007 92 F169ndash175
1 copy 2008 elsevier ltd all rights reserved
self-assessment
Case 1A term male infant born to consanguineous parents is assessed at 24 h of age due to poor feeding profuse yellow watery diar-rhoea and irritability He weighed 32 kg at birth and delivery was uneventful There was no polyhydramnios He has been breastfed since birth On examination he is pale with a non-tender but distended abdomen and reduced bowel sounds His weight is 275 kg and he looks dehydrated Examination is otherwise normal
Initial investigations (normal values in parentheses) showed
sodium 149 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 65 mmollitre (25ndash75)
creatinine 147 μmollitre (40ndash110)
chloride 119 mmollitre (95ndash105)
haemoglobin 172 gdl (140ndash200)
White blood cell count 80 times 109litre (100ndash260)
Platelet count 302 times 109litre (150ndash400)
arterial blood gas
ph 720 (730ndash745)
PcO2 23 kPa (46ndash60)
Bicarbonate 68 mmollitre (220ndash260)
Base excess minus186 mmollitre (minus20 to +20)
lactate 59 mmollitre (06ndash24)
An abdominal X-ray shows distended bowel loops with no intramural thickening or pneumoperitoneum (Figure 1)
He was given nil by mouth and received intravenous fluids and antibiotics His dehydration improved but the metabolic acidosis and diarrhoea persisted despite receiving no enteral feeds and the commencement of total parenteral nutrition Blood and stool cultures were negative
1 Which of the following best describes these results Choose ONE answer ONLY from the followingA Hypernatraemia hyperchloraemic metabolic acidosis
with increased anion gapB Hypernatraemia hyperchloraemic metabolic acidosis
with normal anion gap
Manish Sadarangani BM BCh MA MRCPCH is Clinical Research Fellow
at the Department of Paediatrics University of Oxford Centre for
Clinical Vaccinology and Tropical Medicine Churchill Hospital
Oxford OX3 7LJ UK
Shabna Rajapaksa MB BChir MA MRCPCH is Specialist Registrar in
Paediatrics at the Paediatric Intensive Care Unit John Radcliffe
Hospital Oxford OX3 9DU UK
Nicholas Mann MD FRCP FRCPCH DCH is Consultant Paediatrician at the
Department of Paediatrics Royal Berkshire Hospital Reading RG1
5AN UK
self-assessment
C Hypernatraemic dehydration and compensated metabolic acidosis
D Acute renal failureE Renal tubular acidosis
2 What is the likely diagnosis Choose ONE answer ONLY from the followingA Hirschsprung disease ndash long segmentB Cystic fibrosis with meconium ileusC Microvillus inclusion diseaseD Cowrsquos milk protein intoleranceE Lactose intolerance
3 What is the investigation of choice Choose ONE answer ONLY from the followingA Rectal biopsy with staining for acetylcholine receptorsB Immunoreactive trypsinC Gastrointestinal endoscopy and biopsyD Stool microscopy and cultureE Stool reducing substances
Case 2A 4-year-old boy presents with a 3 d history of jaundice and a florid rash He has had orange urine and there is no change in his stool colour His family originate from Kosovo and have lived in the UK for the last 8 years He has never left the UK There is no history of blood transfusion or sex-ual abuse The grandmother was recently diagnosed with hepatitis B
On examination he is well apyrexial and mildly jaundiced with cervical and axillary lymphadenopathy He has an exten-sive papular rash over the face extremities and trunk (Figure 2) There is 3 cm hepatomegaly with no splenomegaly or ascites Examination is otherwise normal
Figure 1 abdominal X-ray of baby
Paediatrics and child health 184 202 copy 2008 elsevier ltd all rights reserved
self-assessment
Initial investigations are as follows
haemoglobin 110 gdl (113ndash135)
White blood cell count 108 times 109litre (50ndash150)
Platelet count 278 times 109litre (150ndash400)
inr 10 (08ndash12)
aPt ratio 10 (08ndash13)
sodium 140 mmollitre (135ndash145)
Potassium 42 mmollitre (35ndash50)
Urea 56 mmollitre (25ndash75)
creatinine 65 μmollitre (45ndash120)
total bilirubin 66 μmollitre (0ndash15)
conjugated bilirubin 23 μmollitre (0ndash10)
alanine aminotransferase (alt) 2033 iUlitre (0ndash35)
alkaline phosphatase 987 iUlitre (71ndash234)
Gamma-glutamyl transferase (GGt) 870 iUlitre (0ndash51)
1 What is the name of this rash Choose ONE answer ONLY from the followingA Erythema multiformeB Erythema migransC GianottiminusCrosti syndromeD EczemaE Dermatitis herpetiformis
2 What is the most likely diagnosis Choose ONE Answer ONLY from the followingA Autoimmune hepatitisB Hepatitis BC Hepatitis DD Wilson diseaseE Alpha-1 antitrypsin deficiency
3 What is the best means of management Choose ONE answer ONLY from the followingA Isolation until the jaundice disappearsB ImmunosuppressionC Copper chelating agents and genetic counsellingD Patient and family education with consideration of
antiviral agentsE Liver transplantation
Case 3A 10-month-old boy presents with 3 weeks of vomiting and constipation ndash he is passing hard stools every 2ndash3 days He has fallen from the 9th to below the 04th centile in the last 6 weeks He passed meconium within the first 24 h of life On examina-tion he looks pale and there are some dysmorphic features ndash a short nose long philtrum and wide mouth He has normal heart sounds with a grade 3 ejection systolic murmur loudest at the upper right sternal edge Examination is otherwise normal
Initial investigations are as follows
haemoglobin 91 gdl (113ndash141)
total white blood cell count 124 times 109litre (60ndash170)
Platelet count 407 times 109litre (150ndash400)
sodium 144 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 78 mmollitre (25ndash75)
creatinine 78 μmollitre (45ndash120)
albumin 52 glitre (35ndash50)
corrected calcium 384 mmollitre (238ndash263)
Phosphate 167 mmollitre (099ndash157)
1 What is the most likely diagnosis Choose ONE answer ONLY from the followingA HyperparathyroidismB Acute leukaemiaC Williams syndromeD Hypervitaminosis DE Familial hypocalciuric hypercalcaemia
2 Which investigation would be most useful in establishing the diagnosis Choose ONE answer ONLY from the followingA Intact parathyroid hormone assayB Blood filmC Fluorescent in-situ hybridization for 7q1123 deletionD 25-hydroxyvitamin D assayE Urine calciumcreatinine ratio
3 Which of the following treatments would not be suitable for this patient Choose ONE answer ONLY from the followingA Low calcium dietB Normal saline infusionC FurosemideD CorticosteroidsE Bisphosphonates
Case 4A 10-week-old girl presents with a 2-day history of poor feed-ing Her mother has been concerned about weakness since birth She only has a flicker of movement in the arms none in the legs and has a weak cry She has been passing urine and opening her bowels normally She was born at full term by normal delivery and did not require any resuscitation at birth Normal fetal movements were felt antenatally and there was no polyhydramnios She is the first child of non- consanguineous parents and there is no significant family his-tory On examination she is alert and fixing and following appropriately She has a weak cry and a weak suck There is reduced central and peripheral tone with marked head lag
Figure 2 rash found on examination
Paediatrics and child health 184 203 copy 2008 elsevier ltd all rights reserved
self-assessment
Muscle power is grade 3 out of 5 in the arms and legs There is no muscle or tongue fasciculation and she has absent reflexes throughout The remainder of the examination is normal
Electromyogram shows irregular polyphasic motor unit potentials with marked instability consistent with a dener-vating and re-innervating process (Figure 3)
1 Which of the following additional investigations may be helpful Choose ONE answer ONLY from the followingA Nerve conduction studiesB Creatine kinase assayC Muscle biopsyD SMN1 gene analysisE All of the above
2 What is the most likely cause of this childrsquos symptoms Choose ONE answer ONLY from the followingA Congenital myotonic dystrophyB Duchenne muscular dystrophyC PraderminusWilli syndromeD Spinal muscular atrophyE Mitochondrial myopathy
3 What is the mode of inheritance of this disease Choose ONE answer ONLY from the followingA X-linked recessiveB Autosomal recessiveC Autosomal dominantD MitochondrialE Sporadic
Case 5A 13-year-old girl presents with a 3-week history of fever up to 40degC night sweats and headache She has a reduced appetite with some weight loss She has no other specific symptoms She was on holiday in China 7 months ago On examination she looks well and has a temperature of 387degC There is no lymphadenopathy and no rashes Examination is entirely normal
Results of investigations are as follows
haemoglobin 126 gdl (120ndash160)
total white blood cell count 132 times 109litre (43ndash108)
neutrophil count 115 times 109litre (25ndash75)
Platelet count 244 times 109litre (150ndash400)
Blood film neutrophilia with left shift
erythrocyte sedimentation rate 63 mmh (1ndash20)
c-reactive protein 219 mglitre (0ndash5)
Blood culture Streptococcus intermedius
from anaerobic bottle only
csf culture negative
Magnetic resonance imaging (MRI) of the brain shows acute frontal sinusitis with a large intracranial frontal extra-dural empyema (Figure 4)
1 Which of the following would be appropriate management Choose ONE answer ONLY from the followingA A 12-week course of intravenous antibioticsB Drainage of the frontal sinus followed by 2 weeks of
intravenous antibioticsC Drainage of the empyema followed by 2 weeks of
intravenous antibioticsD Drainage of the empyema and the frontal sinus
followed by 2 weeks of oral antibiotics
1151
1152
1153
1154
1155
1156
1157
1158
1159
1200
50ms 1mV
Figure 3 electromyogram recording from the patient Figure 4 Parasagittal section from mri scan of patient
Paediatrics and child health 184 204 copy 2008 elsevier ltd all rights reserved
self-assessment
E Drainage of the empyema and the frontal sinus followed by 8 weeks of intravenous antibiotics
2 Streptococcus intermedius is a potential pathogen in which of the following infections Choose ONE answer ONLY from the followingA Liver abscessB Urinary tract infectionC MeningitisD Thoracic empyemaE Pneumonia
3 Which of the following statements regarding lsquopyrexia of unknown originrsquo in children is false Choose ONE answer ONLY from the followingA Malignancy is the underlying pathology in 5ndash15 of
casesB An aetiology will be found in over 90 of casesC The most common cause is infectionD A rheumatological cause is found in 10ndash20 of casesE Familial Mediterranean fever can occur in children of
non-Mediterranean ethnicity
Answers
Case 11 AThe anion gap is a useful tool to differentiate the causes of a metabolic acidosis It is calculated by the equation
Anion gap = [Na K ] [Cl HCO ]3+ + minus minus+ minus +
It represents the effect of unmeasured anions on the plasma pH and is normally 10ndash18 mmollitre
2 CMicrovillus inclusion disease is a severe autosomal recessive enteropathy that is typically apparent within hours or days after birth It is the second most common cause of protracted diarrhoea in the newborn after infectious causes It is characterized by severe yellow watery diarrhoea and malabsorption due to hypoplasia andor atrophy of the villi of the small intestine secondary to an inherited defect in the brush border membrane This results in severe dehydration malnutrition and metabolic acidosis due to bicarbonate loss from the gut
3 CDiagnosis of microvillus inclusion disease is made on small bowel biopsy Electron microscopy findings are of intracellular brush border inclusions and densely packed apical cytoplasmic vesicular bodies indicating microvillous atrophy There is no cure Treatment is supportive with total parenteral nutrition and consideration of small bowel transplantation
Further reAding
Goulet O ruemmele f causes and management of intestinal failure
in children Gastroenterology 2006 130(suppl 1) s16ndash28
rhoads Jm Vogler rc lacey sr et al microvillus inclusion disease
In vitro jejunal electrolyte transport Gastroenterology 1991
100 811ndash817
Case 21 CGianottindashCrosti syndrome is a distinct self-limiting rash commonly associated with viral infections in children between 2 and 6 years of age It presents as multiple pink to redminusbrown papules or papulovesicles which may be pruritic and can become confluent Gianotti and Crosti initially described the exanthema as associated with hepatitis B virus and they termed it papular acrodermatitis of childhood It can occur in several viral diseases eg hepatitis A B and C coxsackie viruses and cytomegalovirus
2 BHepatitis is a syndrome characterized by inflammation or injury of liver cells which may develop into cell necrosis and subsequently fibrosis andor cirrhosis Biochemically there are raised liver enzymes The degree of transaminase elevation does not correlate with the severity of the disease process Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of viral hepatitis
3 DHepatitis B infection is transmitted via blood sexually or vertically Infection may be acute or chronic Diagnostic markers are the presence of surface antigen (HBsAg) and HBV DNA The presence of e antigen (HBeAg) indicates high infectivity Infected newborns have a 95 risk of becoming carriers this risk decreases with infection acquired later in childhood Approximately 15ndash25 of HBV carriers will die from cirrhosis or hepatocellular carcinoma Extrahepatic findings are more common in older children and include membranous glomerulonephritis and GianottiminusCrosti syndrome Fulminant hepatic failure occurs in severe cases resulting in persistent jaundice encephalopathy and coagulopathy Management includes counselling family members monitoring for ongoing liver disease and consideration of antiviral therapy
Further reAding
Brandt O abeck d Gianotti r Burgdorf W Gianotti crosti
syndrome J Am Acad Dermatol 2006 54 136ndash145
slowik mK Jhaveri r hepatitis B and c viruses in infants and
young children Semin Pediatr Infect Dis 2005 16 296ndash305
Case 31 CHypercalcaemia is uncommon in infancy The most common symptoms in this age group are irritability vomiting and constipation It may be a manifestation of Williams syndrome vitamin D or calcium excess as well as disorders associated with reduced bone formation such as hypophosphatasia or increased bone resorption such as malignancy Occasionally
Paediatrics and child health 184 205 copy 2008 elsevier ltd all rights reserved
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-
SympoSium neonatology
was also reported The Vermont Oxford Network and the SUP-PORT trials will provide further data but at present the delivery room use of CPAP cannot be widely recommended and should be limited to those units experienced in its use or taking part in research
Air or oxygen oxygen has been in widespread use for resuscita-tion at birth since the 1930s and even hyperbaric oxygen was seriously supported in the 1960s For many years there have been concerns about tissue damage from oxygen deprivation during and after resuscitation It became evident in the 1950s that unrestricted oxygen therapy could have serious conse-quences for future vision More recently concerns have been raised about potential adverse effects on respiratory physiology cerebral circulation and tissue damage from oxygen free radicals even during resuscitation A meta-analysis of four human studies demonstrated a reduction in mortality and no evidence of harm in infants resuscitated in air versus 100 oxygen3233 However there are several significant methodological concerns with these studies and the results should be interpreted with caution There is insufficient evidence to recommend any specific concentration of oxygen to be used for newborn resuscitation Monitoring the oxygen saturation of babies may be helpful but as yet there are no time-related normal target ranges and healthy term babies may take up to 10 min to achieve preductal oxygen saturation of greater than 95 and up to 60 min to achieve this postductally
There is therefore equipoise which would be open to an appropriate randomized controlled trial In the meantime the evidence only supports use of either 21 or 100 oxygen It is provoking to realize that if air had been in constant use since the 1930s there would be insufficient evidence for use of supple-mental oxygen
Circulation
Early resuscitation (temperature control airway breathing) provides oxygenated blood in the pulmonary arterioles which if returned to the heart causes the rate to increase34 If due to acidosis and hypoxia the circulation is ineffective then chest compressions may be needed They should be commenced when the heart rate remains below 60min despite effective airway and breathing management127 The best technique is using two hands to encircle the chest1 A ratio of three compressions to one breath is internationally accepted127 but has no evidence to support it Research has shown that neither compressions nor drugs will work in this situation without oxygenated blood so effective lung aeration and ventilation is essential A logical approach would be to fill the alveoli with air and to compress the chest until they are empty However training and teamwork require an agreed ratio which has therefore not changed since guidelines were first agreed internationally Success is assessed by an increase in heart rate which should therefore be assessed every 30 s Compressions stop when the spontaneous heart rate is greater than 60 beatsmin
In hypoxic newborn animal models successful resuscitation can restore cardiac output and blood pressure to levels above baseline within 5ndash10 min However it should be noted that there is a decline to 30 lower than basal levels within 2 h and that blood pressure is relatively spared suggesting an even greater
paeDiatRiCS anD CHilD HealtH 184 16
reduction in tissue perfusion This should be considered in the later care of any neonate who was hypoxic at birth
Drugs
Neonatal bradycardia at birth is almost always due to hypoxia plusmn acidosis and therefore drugs are rarely needed Adrenaline (epi-nephrine) is reported as being used in between 1 and 4 babies per 2000 births which is a large variation in practice Reported success is also variable and must be interpreted in light of this variation The use of drugs in extremely premature infants is con-troversial Some data suggested good outcomes for babies below 28 weeksrsquo gestation given adrenaline but these were flawed by high numbers of babies receiving resuscitative drugs some before the airway had been appropriately managed Audit data now suggest a poor outcome such that many clinicians would now council against the use of adrenaline and other drugs to resuscitate extremely premature newborn babies
Adrenaline (epinephrine)In 2003 a Cochrane review of randomized controlled trials involv-ing adrenaline use for resuscitation of neonates was unable to identify a single clinical trial35 Despite the lack of human neo-natal data animal models show the potential of adrenaline in asphyxial cardiac arrest and it is reasonable to use it when ade-quate ventilation and chest compressions have failed to increase the heart rate above 60 beatsmin Use 10ndash30 μgkg intrave-nously and preferably via an umbilical venous line The tracheal route cannot be recommended but if used it is likely that doses within this range will be ineffective and 100 μgkg might be tried However the safety of such doses has not been studied
BicarbonateThe use of bicarbonate has long been controversial but many of the concerns relate to the rapid correction of acidosis in neonates after resuscitation or the routine use of bicarbonate infusion nei-ther of which can be advocated There are no published human neonatal data to support its use although some exist from animal studies Animal data have also shown that the binding of adren-aline to receptors in the myocardium is significantly impaired by lactic acidosis and recent work on human lymphocyte beta-adrenergic receptors supports this view Whether this is also true of the more important alpha receptors is unknown In practice reversing intracardiac acidosis may improve myocardial function and assist in achieving a return of spontaneous circulation 1ndash2 mmolkg of bicarbonate may be given but this remains a contro-versial area
VolumeVolume expansion should only be given when it is suspected that the baby has suffered blood loss or the infant appears to be in shock (pale poor perfusion weak pulse) and has not responded adequately to other resuscitative measures If there is no history suggestive of blood loss shock is most likely to be due to myo-cardial dysfunction in which case fluids should be administered cautiously The most logical replacement fluid would be blood but in its absence isotonic crystalloid rather than albumin is the solution of choice given in 10 mlkg aliquots and observing the response Three randomized trials in neonates have shown
9 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
isotonic crystalloid to be as effective as albumin for the treat-ment of hypotension but none has examined either the relative or actual effectiveness in resuscitation A recent blinded randomized study comparing normal saline albumin or no volume expansion in a normovolaemic asphyxiated neonatal animal model showed that volume expansion was not beneficial and made a number of parameters worse36
NaloxoneNaloxone is not recommended as part of the initial resuscita-tion of newborns with respiratory depression Before it is given supporting ventilation should have restored the heart rate and colour The dose is 100 μgkg intravenously or intramuscularly Tracheal administration cannot be recommended Although administration of naloxone to neonates who have been exposed to maternal opioids during labour is a practice of long-standing it lacks the proper evidence of efficacy
Non-response to resuscitation
There are few more frightening situations professionally than applying the correct interventions in resuscitating or stabilizing a baby and getting no response Each stage must be adequately performed before moving onto the next and this requires regular reassessment When experienced help is needed at a newborn resuscitation it is usually the airway and ventilation that require correction If the heart rate does not increase this usually means that the lungs have not been successfully aerated In some cases however it may mean that the heart cannot respond as the cir-culation is inadequate In this situation the only way to check that the lungs have been successfully aerated is to see the chest move with ventilation or to obtain evidence of ventilation from a detector of exhaled carbon dioxide If you do not see chest movement after another five breaths the most likely cause is an obstructed airway either due to incorrect positioning or because the jaw has not been drawn forwards An oropharyngeal airway can be very helpful at this point especially in the term baby Only very occasionally is the airway blocked by mucus vernix blood or meconium but if the airway is guaranteed and there is no heart rate response or chest movement this should be sought by direct suction of the trachea even in the absence of any meconium staining of liquor Pneumothoraces can occur spontaneously after delivery but are rare at resuscitation carried out with pressure-limited devices Equally rare are diaphragmatic hernias that have not been diagnosed antenatally giving problems at resuscitation
If the chest is moving but the heart rate has not responded to resuscitation consider rare possibilities such as fetal blood loss pneumothorax or heart block (mothers with undiagnosed systemic lupus erythematosis delivered for fetal bradycardia) as possibilities With adequate ventilation there is no evidence of oxygen concentrations less than 100 being responsible for prolonged bradycardia or failure to respond although current practice would support increasing the delivered oxygen concen-tration if resuscitation had been commenced using air
Outcome
The prognosis for the full-term baby subjected to sudden acute asphyxia is usually good provided the episode does not last for
paeDiatRiCS anD CHilD HealtH 184 17
long Most babies resuscitated from primary apnoea have no sequelae secondary to the resuscitation Many babies who start to breathe again regularly within 20 min of the circulation being restored recover completely but it is rare for a baby who is still gasping after 30 min to recover
The prognosis for the preterm baby of less than about 34 weeksrsquo gestation subjected to severe acute anoxia is less predict-able This is because of the risk of secondary intraventricular haemorrhage or periventricular intracerebral haemorrhage andor infarction after even a relatively brief asphyxial episode espe-cially in the period immediately around birth
The effects of chronic hypoxia are also difficult to predict but a reasonably clear idea of the extent of the problem should be obtainable within 36ndash48 h of the original chronic asphyxial insult A mild short-lasting state of hyperexcitability usually car-ries a good prognosis even if there is seizure activity but more severe symptoms can be associated with permanent handicap This is seen especially in infants with encephalopathy requiring ventilation
REFERENCEs
1 Biarent D Bingham R Richmond S et al european Resuscitation
Council guidelines for Resuscitation 2005 Section 6 paediatric life
support Resuscitation 2005 67(suppl 1) S97ndashS133
2 international liaison Committee on Resuscitation part 7 neonatal
resuscitation Resuscitation 2005 67 293ndash303
3 Singh J Santosh S Wyllie J mellon a effects of a course in
neonatal resuscitation - evaluation of an educational intervention
on the standard of neonatal resuscitation Resuscitation 2006 68
385ndash389
4 palme-Kilander C methods of resuscitation in low-apgar-score
newborn infants - a national survey Acta Paediatr 1992 81
739ndash744
5 Kroll l twohey l Daubeney p et al Risk factors at delivery and
the need for skilled resuscitation Eur J Obstet Gynecol Reprod Biol
1994 44 175ndash177
6 Wyllie Jp Resuscitation of the newborn The Foundation Years
2007 3(4) 153ndash157
7 Richmond S ed newborn life Support Resuscitation at Birth
london Resuscitation Council 2006
8 Ceriani Cernadas Jm Carroli g pelligrine l et al the effect of timing
of cord clamping on neonatal venous hematocrit values and clinical
outcome at term a randomized controlled trial Pediatrics 2006
117 e779ndashe786
9 mercer JS Vohr BR mcgrath mm padbury JF Wallach m oh W
Delayed cord clamping in very preterm infants reduces the incidence
of intraventricular hemorrhage and late-onset sepsis a randomized
controlled trial Pediatrics 2006 117 1235ndash1242
10 Dahm lS James lS newborn temperature and calculated heat loss
in the delivery room Pediatrics 1972 49 504ndash513
11 Stephenson J Du J tk o the effect of cooling on blood gas
tensions in newborn infants J Pediatr 1970 76 848ndash852
12 gandy gm adamsons Jr K Cunningham n Silverman Wa James lS
thermal environment and acid-base homeostasis in human infants
during the first few hours of life J Clin Invest 1964 43 751ndash758
13 gluck l Kulovich mV eidelman ai et al Biochemical development
of surface activity in mammalian lung pulmonary lecithin synthesis
0 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
in the human fetus and newborn and etiology of the respiratory
distress syndrome Pediatr Res 1972 6 81ndash99
14 Vohra S Roberts RS Zhang B Janes m Schmidt B Heat loss
prevention (Help) in the delivery room a randomised controlled
trial of polyethylene occlusive skin wrapping in very preterm infants
J Pediatr 2004 145 750ndash753
15 owen CJ Wyllie Jp Determination of heart rate in babies at birth
Resuscitation 2004 60 213ndash217
16 orsquoDonnell Cp Kamlin Co Davis pg Carlin JB morley CJ Clinical
assessment of infant colour at delivery Arch Dis Child Fetal
Neonatal Ed 2007 92 F465ndashF467
17 international liaison Committee on Resuscitation part 13 neonatal
Resuscitation guidelines Circulation 2005 112(suppl 24)
iV188ndashiV195
18 leone ta Rich W Finer nn neonatal intubation Success of
pediatric trainees J Pediatr 2005 146 638ndash641
19 orsquoDonnell Cp Kamlin Co Davis pg morley CJ endotracheal
intubation attempts during neonatal resuscitation success
rates duration and adverse effects Pediatrics 2006 117
e16ndash21
20 Repetto Je Donohue pa-CpK Baker SF Kelly l nogee lm use of
capnography in the delivery room for assessment of endotracheal
tube placement J Perinatol 2001 21 284ndash287
21 gandini D Brimacombe JR neonatal resuscitation with laryngeal
mask airway in normal and low birth weight infants Anesth Analg
1999 89 642ndash643
22 esmail n Saleh m ali a laryngeal mask airway versus endotracheal
intubation for apgar score improvement in neonatal resuscitation
Egypt J Anesthiol 2002 18 115ndash121
23 Wiswell te gannon Cm Jacob J et al Delivery room management
of the apparently vigorous meconium-stained neonate results of
the multicenter international collaborative trial Pediatrics 2000
105 1ndash7
24 Vain ne Szyld eg prudent lm Wisewell te aguilar am Vivas ni
oropharyngeal and nasopharyngeal suctioning of meconium-stained
neonates before delivery of their shoulders multicentre randomised
controlled trial Lancet 2004 364 597ndash602
25 Bjorklund lJ ingimarsson J Curstedt t larsson a Robertson B
Werner o lung recruitment at birth does not improve lung function
in immature lambs receiving surfactant Acta Anaes Scand 2001 45
986ndash993
26 Bjorklund lJ ingimarsson J Curstedt t et al manual ventilation
with a few large breaths at birth compromises the therapeutic effect
of subsequent surfactant replacement in immature lambs Pediatr
Res 1997 42 348ndash355
paeDiatRiCS anD CHilD HealtH 184 17
27 taskar V John J evander e Robertson B Jonson B Surfactant
dysfunction makes lungs vulnerable to repetitive collapse and re-
expansion Am J Respir Crit Care Med 1997 155 313ndash320
28 muscedere Jg mullen JB gan K Slutsky aS tidal ventilation at low
airway pressures can augment lung injury Am J Respir Crit Care Med
1994 149 1327ndash1334
29 nilsson R grossman g Robertson B Bronchiolar epithelial lesions
induced in the premature rabbit neonate by short periods of artificial
ventilation Acta Pathol Microbiol Scand 1980 88 359ndash367
30 probyn me Hooper SB Dargaville pa et al positive end expiratory
pressure during resuscitation of premature lambs rapidly improves
blood gases without adversely affecting arterial pressure Pediatr
Res 2004 56 198ndash204
31 Wood Fe morley CJ Dawson Ja et al improved techniques
reduce face mask leak during simulated neonatal resuscitation
study 2 Arch Dis Child Fetal Neonatal Ed in press doi101136
adc2007117788
32 tan a Schulz a orsquoDonnell CpF Davis pg air versus oxygen for
resuscitation of infants at birth Cochrane Database Syst Rev 2004
(3) CD002273
33 Davis pg tan a orsquoDonnell Cp Schulze a Resuscitation of newborn
infants with 100 oxygen or air a systematic review and meta-
analysis Lancet 2004 364 1329ndash1333
34 Dawes g Fetal and neonatal physiology Chicago year Book
publisher 1968 p 141ndash159
35 Ziino aJa Davies mW Davis pg epinephrine for the resuscitation
of apparently stillborn or extremely bradycardic newborn infants
Cochrane Database Syst Rev 2003 (2) CD003849
36 Wyckoff m garcia D margraf l perlman J laptook a Randomized
trial of volume infusion during resuscitation of asphyxiated neonatal
piglets Pediatr Res 2007 61 415ndash420
Practice points
bull Resuscitation at birth is different from that at all other times
of life
bull a standard approach can be applied to most newborn
resuscitation
bull guidelines are based on a rigorous evaluation of evidence
where possible
bull evidence is sparse but evolving
bull most preterm babies require stabilization rather than
resuscitation
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Acidndashbase physiology and blood gas interpretation in the neonateSusern tan
morag Campbell
Abstractacidndashbase balance describes the complex processes that work to main-
tain a stable extracellular pH for optimal cellular function the process
of balancing the production and neutralization of tissue acid provides a
great challenge for newborn infants who have significantly higher rates
of acid production than adults Factors which help maintain a stable
acidndashbase balance include buffers the respiratory system and renal sys-
tem Both intracellular and extracellular buffers resist changes in pH
the most important extracellular buffer system for maintaining stable
pH is the bicarbonate system in response to acidosis or alkalosis the
respiratory system balances the production of acid with the clearance
of Co2 by altering respiratory rate the kidneys provide a delayed but
sustained response to pH imbalance by excreting either acidic or alkaline
urine in response to systemic acidosis and alkalosis respectively in sick
premature infants these systems have a limited capacity completely to
control pH this review discusses the physiology of the three systems
which control acidndashbase balance patterns of clinical abnormalities in
acidndashbase status and their underlying causes are discussed We present
a systematic approach to blood gas analysis and interpretation in new-
born infants
Keywords acidosis alkalosis bicarbonate bloodndashgas analysis
metabolic pH
Introduction
Blood gas analysis is a routine procedure performed on newborn babies receiving respiratory support in the neonatal intensive care The combination of invasive and non-invasive assessment of ventilation and oxygenation enables clinicians appropriately to modify respiratory care according to each individual babyrsquos rapidly changing clinical status
Understanding the fundamentals of acidndashbase balance helps us to use blood gas analysis not only to assess respiratory sta-tus but also to provide information on metabolic status and the adequacy of tissue perfusion
Susern Tan MBBS MRCP is Clinical Fellow at the Neonatal Intensive Care
Unit 6th Floor North Wing St Thomasrsquo Hospital London SE1 7EH UK
Morag Campbell MBChB MRCP is Consultant Neonatologist at the
Neonatal Intensive Care Unit 6th Floor North Wing St Thomasrsquo
Hospital London SE1 7EH UK
paeDiatRiCS anD CHilD HealtH 184 17
What is understood by acid-base balance
Acidndashbase balance refers to the complex physiological processes used by the body to maintain a stable extracellular pH1 A serum pH within the range of 735ndash745 provides the ideal environment for cellular metabolism Maintaining a stable pH is critical as the metabolic activity of proteins is pH dependent and small changes in hydrogen ion (H+) concentration can potentially alter physio-logical function
Acids are substances that yield free H+ in solution while a base accepts H+ and in solution combines with an acid to neu-tralize it In the normal metabolic state H+ are continuously pro-duced and neutralized to maintain a steady pH balance12 The rate of H+ production is two to three times higher in neonates because of their rapid growth rates and increased acid production from protein turnover and bone mineralization The challenge of maintaining a stable pH through processing and neutralizing H+ is therefore greatest in newborn infants
Using exact values of H+ concentration to assess acidndashbase status is cumbersome and it is more commonly expressed as pH defined by the equation
pH = minuslog H+
Maintaining acidndashbase balance
The balance between production and excretion of acids in the body is controlled by buffer systems which have an immediate effect and by the respiratory and the renal systems
Buffer systemsBuffer solutions resist change in pH when acid or alkali is added due to their capacity to absorb or give up H+ The three main buffer systems in the body are the bicarbonate phosphate and protein systems1ndash3 The protein and phosphate buffer systems are intracellular and act as lsquosinksrsquo for extracellular H+ which are exchanged with intracellular potassium (K+) and sodium ions (Na+) In an acute metabolic acidosis hyperkalaemia may develop due to this H+ exchange4
The bicarbonate buffer system is extracellular and consists of a mixture of carbonic acid (H2CO3) and sodium bicarbon-ate (NaHCO3) This buffer system helps maintain a stable pH by soaking up excess H+ with HCO3
minus which in solution forms carbonic acid (H2CO3) Carbonic acid is a weak acid and readily dissociates to give CO2 which is transported in dissolved form to the lungs for excretion
H+ + HCO3minus harr H2CO3 harr H2O + CO2
The bicarbonate system therefore completes the neutraliza-tion of excess H+ and a stable plasma pH is maintained The relationships between pH HCO3
minus and CO2 in this system are described by the HendersonndashHasselbalch equation15
pH = 61 + log HCO3minus003 times CO2
where 61 is the log of the dissociation coefficient of carbonic acid and 003 the solubility of CO2 in plasma Buffers are most potent when there are equal amounts of H+ and HCO3
minus in solution The
2 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
bicarbonate system is not a potent buffer however as HCO3minus
and CO2 are readily altered by the body this system plays a very powerful role in pH homeostasis15
Respiratory regulationThe respiratory system adapts within minutes to hours as part of the acute response to acidosis This system modifies pH by balancing production of H+ with ventilatory clearance of CO2
H+ directly stimulates chemoreceptors in the respiratory cen-tre of the brainstem producing an increase in respiratory rate26 The response to respiratory acidosis is very rapid as CO2 easily diffuses across the bloodndashbrain barrier however in metabolic acidosis compensation is delayed until plasma bicarbonate fully equilibrates with cerebrospinal fluid (CSF) bicarbonate There is an inverse relationship between alveolar ventilation and partial pressure of dissolved carbon dioxide (PaCO2) a reduction in alveolar ventilation raises PaCO2 and decreases pH Changes in pH therefore affect alveolar ventilation and conversely changes in alveolar ventilation cause significant changes in pH
Renal regulationThe kidneys provide a delayed but sustained response to acidndashbase imbalances by excreting either acidic or alkaline urine In full-term and preterm babies the capacity for acid excretion and bicarbonate reabsorption is reduced as glomerular filtration rates are low and tubular function immature7 Renal function matures with gestation postnatal age and glucocorticoid and thyroid hormones78 Due to their limited capacity to preserve HCO3
minus newborn infants have lower serum bicarbonate levels and are predisposed to acidosis7
Bicarbonate is not effectively reabsorbed due to its size and electrical charge Instead intraluminal HCO3
minus combines with secreted H+ in tubular luminal fluid to produce carbonic acid which dissociates to give H2O and CO2 This CO2 diffuses into tubular cells combines with intracellular H2O and forms carbonic acid which liberates HCO3
minus and H+ HCO3minus is then
recovered to the circulation by exchange for chloride ions (Clminus) through the basal cell membrane247
Renal acid secretion occurs at all sites except the loop of Henle Primary active transport accounts for 5 and secondary for the remaining 95 of total H+ excretion Secondary trans-port involves an exchange between luminal Na+ and intracel-lular H+ Both ions bind to a membrane transport protein The Na+ concentration gradient between the tubular lumen and cells enables Na+ drag into the cell which generates energy to fuel active H+ excretion into the tubular lumen1ndash47
Quantifying acidosis
Standard base excess is a calculated value derived from PaCO2 and pH It is expressed as the mmollitre of base above or below normal buffer bases required to correct the pH to 74 at a PaCO2 of 40 mmHg A negative base excess or base deficit indicates an acidosis while a positive base excess indicates a relative alkalosis15
Anion gap is the measured difference between anions and cations in the blood
Anion gap = (Na+ + k+) minus (HCO3+Clminus)
paeDiatRiCS anD CHilD HealtH 184 17
Calculation of the anion gap enables clinicians better to define the underlying cause of a metabolic acidosis9 The common causes of an increased anion gap acidosis in neonates include lactic acidosis due to tissue hypoperfusion and hypoxia it may also be seen with certain inborn errors of metabolism and in uraemia910 The anion gap can help distinguish between the rela-tively benign non-anion gap hyperchloraemic acidosis seen in premature infants and a pathological lactic acidosis due to poor end-organ perfusion1011
Strong ion theory
Stewart described a complex acidndashbase model which proposed that H+ concentration results from the dissociation of water which is influenced by PaCO2 the strong ion difference and plasma weak acids12
Strong ions are ions that dissociate at normal body pH and include Na+ K+ and Clminus Weak acids in plasma which contrib-ute include albumin inorganic phosphate and plasma proteins their concentrations do not change with pH and are therefore a constant The effect of these factors and other unmeasured tissue ions on acidndashbase status can be quantified by the calculation of the strong ion gap (SIG)112 In the neonatal unit it is perhaps more important that we consider how principles of this model may relate to acidndashbase status rather than fully to quantify the SIG Theoretically low albumin and phosphate levels which fre-quently occur in premature infants by reducing the concentra-tion of weak acids can produce a relative alkalosis while high phosphate levels in renal failure may contribute to acidosis
Tissue oxygenation
Oxygenation is closely linked to acidndashbase status as optimal cel-lular function requires oxygen to fuel aerobic metabolism and produce energy In hypoxic conditions anaerobic metabolism predominates which is energy inefficient and results in a lactic acidosis1011
Tissue oxygen availability is related to regional blood flow haemoglobin level and haemoglobin oxygen affinity Arterial blood gases measure the partial pressure of dissolved oxygen (PaO2) which represents a small component of total oxygen con-tent the majority being transported bound to haemoglobin The relationship between percentage haemoglobin saturation (SaO2) and PaO2 is described by the sigmoidal oxyhaemoglobin disso-ciation curve which enables us to relate the two measures to each other235 The affinity of haemoglobin for oxygen is altered by local tissue factors Increases in temperature H+ PaCO2 and 23-diphosphoglycerate (DPG) levels shift the oxyhaemoglobin dissociation curve to the right reducing affinity for oxygen Decreases in temperature H+ PaCO2 and 23-DPG levels shift the curve to the left increasing oxygen affinity1ndash35 In the body haemoglobin oxygen affinity continuously changes increasing in the lungs to enable efficient oxygen uptake and decreasing at tissue level to provide efficient oxygen delivery to metabolically active tissues
Avoiding both hypoxia and hyperoxia is important in the neo-natal unit as deleterious effects of hypoxia are seen in infants with pulmonary hypertension1314 while hyperoxia is associated with an increased incidence of retinopathy of prematurity1516
3 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Clinical acidndashbase imbalances
Clinical acidndashbase imbalances can be respiratory metabolic or a mixture of both These abnormalities may be corrected by the acidndashbase regulatory mechanisms in the body in an attempt to maintain normal pH (Figure 1)
Respiratory acidosisThis occurs when any disorder leads to decreased alveolar ventilation Common causes of respiratory acidosis are listed in Table 1 Reduced respiratory clearance of CO2 means more dissolved CO2 accumulates in the plasma leading to increased production of carbonic acid and H+ Through chemoreceptor stimulation respiratory acidosis rapidly alters ventilation in an attempt to reduce CO226 Chemoreceptor mediated ventila-tory increases may only partly adjust in premature infants with underlying lung disease In babies with a sustained respiratory acidosis eg in chronic lung disease then metabolic compen-sation occurs through increased renal excretion of H+ and reabsorption of HCO3
minus slowly restoring pH to around 80 of normal47
paeDiatRiCS anD CHilD HealtH 184 17
The management of PaCO2 levels in infants receiving mechan-ical ventilation has important clinical implications Premature babies have impaired cerebral autoregulation17 and adverse neurological sequelae are reported in association with high PaCO2 levels18ndash20 Ventilation strategies which advocate lsquoper-missive hypercarbiarsquo have been developed to minimize airways damage from mechanical ventilation21 Published data suggest pulmonary benefits however the safe level of PaCO2 remains to be defined in premature infants2021
Respiratory alkalosisThis occurs when more CO2 is excreted than is produced by the body Pathological conditions leading to respiratory alkalosis are rare Hyperventilation in the neonatal setting is often iatrogenic or may be due to disorders in brainstem control of breathing including hypoxicndashischaemic encephalopathy or primary central nervous system abnormalities (see Table 1)
If respiratory alkalosis is sustained it may be compensated for by reduced reabsorption of filtered bicarbonate Reported adverse associations of low PaCO2 include periventricular leuco-malacia and intraventricular haemorrhage1922
K+
H+
Overventilation
CO2 + H2O harr H2CO3 harr H+ + HCO3ndash
Bicarbonate Buffer
Intracellular Buffer
uarr H+ excretionuarr HCO3
ndash absorption
uarr buffered H+
(NH4+ H2PO4
ndash)uarr ventilation rate
RespiratoryAcidosis
MetabolicAcidosis
darr CO2and uarr pH
RespiratoryAlkalosis
MetabolicAlkalosis
darr H+ anduarr pH
darr ventilation rate
uarrCO2
and darr pH
darr H+ excretiondarr HCO3
ndash absorption
uarrH+ and
darr pH
Brain
Brain
Intracellular Buffer
H+
K+
Sepsis
HypoxiaRDS
Metabolismand growth
Diuretics
Airwayobstruction
Neuromuscularproblems
IEM
Gastric losses
+ +
ndash -
Renal BufferRespiratory Buffer
Figure 1 mechanisms for regulation of extracellular pH iem inborn errors of metabolism RDS respiratory distress syndrome
4 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Common causes of acidndashbase imbalances
pH PCO2 H2CO3 Base excess Common neonatal causes
Respiratory acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
uarr normal normal bull upper airway obstruction choanal atresia
pierre-Robin sequence
bull lung abnormalities respiratory distress
syndrome transient tachypneoa of
newborn pneumonia meconium aspiration
syndrome pulmonary hypoplasia
congenital pulmonary malformations
bull Central hypoventilation hypoxic-ischaemic
encephalopathy intracranial haemorrhage
bull neuromuscular insufficiency congenital
myopathies congenital neuropathies
bull iatrogenic inadequate ventilatory settings
Compensated lower limit
of normal
uarr uarr gt+3
metabolic acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
normal darr ltminus3 increased anion gap
bull lactic acidosis sepsis hypoperfusion
shock necrotizing enterocolitis
bull inorganic acidosis inborn errors of
metabolism renal failure
normal anion gap
bull increased gastrointestinal H2Co3 losses
ileostomy diarrhoea
bull Renal tubular acidoses
Compensated lower limit
of normal
darr darr ltminus3
Respiratory alkalosis Uncompensated gt 745 darr normal normal bull iatrogenic excessive ventilatory settings
bull Compensatory hyperventilation hypoxic-
ischaemic encephalopathy
Compensated higher limit
of normal
darr darr ltminus3
metabolic alkalosis Uncompensated gt 745 normal uarr gt+3 bull gastric losses vomiting non-replacement
of excessive nasogastric aspirates
bull thiazide and loop diuretics
bull Hypokalaemia
Compensated higher limit
of normal
uarr uarr gt+3
Table 1
Metabolic acidosisThis frequently affects infants in the neonatal unit and has many causes1011 (see Table 1) There may be overproduction of tissue acid impaired acid clearance gastrointestinal loss of bicarbonate or an exogenous increased acid load eg chloride total paren-teral nutrition (TPN) or albumin1ndash323
Calculation of the anion gap to distinguish an increased anion gap acidosis from a non-anion gap acidosis is important both for treatment and prognosis1011 Acidosis stimulates respiratory compensation but this is limited in unstable infants Similarly renal compensation with improved HCO3
minus conservation is con-strained by tubular immaturity Treatment of the acidosis should be directed at the underlying cause eg hypoxia hypotension or excess Clminus rather than by administration of base
Metabolic alkalosisThis is unusual in neonates and is most frequently seen in infants with chronic lung disease or heart failure who are receiving diuretics Diuretics cause alkalosis by increasing renal fluid and Na+ losses An active process to reabsorb Na+ occurs in tubule cells which through enhanced H+ secretion and HCO3
minus reab-sorption produce alkalosis27
paeDiatRiCS anD CHilD HealtH 184 17
Metabolic alkalosis may also occur with excessive loss of gas-tric contents eg protracted vomiting or inadequate replacement of nasogastric aspirates (see Table 1)
Interpreting blood gases
Blood gas measurements can provide important diagnostic and prognostic information and a systematic approach to blood gas analysis is described in Table 2 The clinical management of infants with abnormal gases requires a good understanding of acidndashbase physiology and tissue oxygenation and an apprecia-tion of factors which may affect the reliability of samples
Arterial blood sampling is the gold standard however indwelling arterial catheters and arterial stab samples are usually restricted to infants who are critically ill or those who require sig-nificant ongoing intervention Gases are most frequently measured in capillary or venous samples which correlate well with arterial samples for PaCO2 pH and base excess in babies and children receiving intensive care These correlations however are not valid in infants with peripheral vasoconstriction and hypotension2324
Non-invasive monitoring techniques may enable us to reduce the frequency of blood gas sampling Transcutaneous monitoring
5 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
A systematic approach to blood gas analysis
1 Collect the relevant information
bull type of gas ndash capillary or arterial
bull Current respiratory support ndash document level
bull transcutaneous Co2 and Sao2 levels
bull Clarify no significant clinical events before sampling
2 pH accept a range between 730 and 745 in newborn
babies this is lower than in older children is there an
alkalosis (pH gt 745) or an acidosis (lt 730)
3 Co2 aim for a range between 45 and 65 kpa a paCo2 level
more than 65 kpa suggests inadequate alveolar ventilation
while less than 45 kpa suggests hyperventilation Correlate
values with non-invasive measures
4 o2 Can only be assessed from arterial gases aim for pao2
between 60 and 80 kpa Correlate results with pulse
oximetry levels
5 HCo3 and base excess normal HCo3 level is between 20 and
24 mmollitre and bases excess +3 to minus3
6 anion gap look at the anion gap and lactate to help identify
the cause of an acidosis normal lactate levels should be less
than 2 mmollitre
7 Respiratory or metabolic compensation look at the pH and
assess whether it is appropriate for the Co2 level or is there
evidence of compensation
8 interpret use both the clinical history and blood gas
findings to help you identify the primary problem aim your
management at treating the underlying cause
9 Reassess if clinical management changes have been made
repeat the blood gas after an appropriate time interval to
ensure improvement
Table 2
provides a highly accurate and reliable method for measuring PaCO2 through the skin it can however be technically difficult may cause tissue damage and is of limited reliability when peripheral perfusion is reduced25 Continuous end-tidal CO2 measurements correlate well with arterial CO2 values in patients with normal ventilation and perfusion however in babies with lung disease alveolar collapse small tidal volumes and rapid respiratory rates can make these measurements unreliable26 Despite its limitations transcutaneous monitoring provides the best method for CO2 trend monitoring in the neonatal intensive care unit (NICU)25
Oxygen saturation levels can be continuously measured non-invasively using pulse oximetry While oximetry is easy to perform and accurate on occasion SaO2 levels obtained may be unreliable when tissue perfusion is poor or with movement artefact SaO2 monitoring is highly sensitive at detecting hypoxia but is limited in detecting hyperoxia as at levels more than 90 small changes in SaO2 may result in unacceptably large increases in PaO227 It is therefore essential that SaO2 alarm limits are set for all neonates receiving respiratory support to detect hypoxia and prevent hyperoxia1627
Continuous non-invasive monitoring provides invaluable information when managing complex infants in the NICU but it does not replace the need for regular blood gas analysis
paeDiatRiCS anD CHilD HealtH 184 17
ReFeRenCeS
1 Kellum Ja Determinants of blood pH in health and disease
Crit Care 2000 4 6ndash14
2 Quigley R Baum m neonatal acid base balance and disturbances
Semin Perinatol 2004 28 97ndash102
3 Brouillette Rt Waxman DH evaluation of the newbornrsquos blood gas
status Clin Chem 1997 43 215ndash221
4 Chan JC acid-base disorders and the kidney Adv Pediatr 1983 30
401ndash471
5 Siggaard-andersen o the pH-log pCo2 blood acidndashbase nomogram
revised Scand J Lab Invest 1962 14 598ndash604
6 Saetta m mortola Jp interaction of hypoxic and hypercapnic stimuli
on breathing pattern in the newborn rat J Appl Physiol 1987 62
506ndash512
7 Baum m Quigley R postnatal renal development in Seldin DW
giebisch g eds the kidney physiology and pathophysiology new
york lippincott Williams and Wilkins 2000 p 703ndash726
8 ortiz la Quan a Weinberg a et al effect of prenatal
dexamethasone on rat renal development Kidney Int 2001 59
1663ndash1669
9 gabow pa Kaehny WD Fennessey pV goodman Si gross pa
Schrier RW Diagnostic importance of an increased serum anion gap
N Engl J Med 1980 303 854ndash858
10 lorenz Jm Kleinman li markarian K oliver m Fernandez J Serum
anion gap in the differential diagnosis of metabolic acidosis in
critically ill newborns J Pediatr 1999 135 751ndash755
11 Deshpande Sa platt mp association between blood lactate and
acid-base status and mortality in ventilated babies Arch Dis Child
1997 76 F15ndash20
12 Stewart pa modern quantitative acid-base chemistry Can J Physiol
Pharmacol 1983 61 1444ndash1461
13 Dakshinamurti S pathophysiologic mechanisms of persistent
pulmonary hypertension of the newborn Pediatr Pulmonol 2005
39 492ndash503
14 mourani pm ivy DD gao D abman SH pulmonary vascular
effects of inhaled nitric oxide and oxygen tension in
bronchopulmonary dysplasia Am J Respir Crit Care Med 2004
170 1006ndash1013
15 Deulofeut R Critz a adams-Chapman i Sola a avoiding hyperoxia
in infants le 1250 g is associated with improved short- and long-
term outcomes J Perinatol 2006 26 700ndash705
16 Chow lC Wright KW Sola a Can changes in clinical practice
decrease the incidence of severe retinopathy of prematurity in very
low birth weight infants Pediatrics 2003 111 339ndash345
17 Boylan gB young K panerai RB Rennie Jm evans DH Dynamic
cerebral autoregulation in sick newborn infants Pediatr Res 2000
48 12ndash17
18 Kaiser JR gauss CH pont mm Williams DK Hypercapnia during
the first 3 days of life is associated with severe intraventricular
hemorrhage in very low birth weight infants J Perinatol 2006 26
279ndash285
19 Fabres J Carlo Wa phillips V Howard g ambalavanan n Both
extremes of arterial carbon dioxide pressure and the magnitude of
fluctuations in arterial carbon dioxide pressure are associated with
severe intraventricular hemorrhage in preterm infants Pediatrics
2007 119 299ndash305
20 thome uH Carroll W Wu tJ et al outcome of extremely preterm
infants randomized at birth to different paCo2 targets during the
first seven days of life Biol Neonate 2006 90 218ndash225
6 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
21 Carlo Wa Stark aR Wright ll et al minimal ventilation to prevent
bronchopulmonary dysplasia in extremely-low-birth-weight infants
J Pediatr 2002 141 370ndash374
22 okumura a Hayakawa F Kato t et al Hypocarbia in preterm
infants with periventricular leukomalacia the relation between
hypocarbia and mechanical ventilation Pediatrics 2001 107
469ndash475
23 peters o Ryan S matthew l Cheng K lunn J Randomised
controlled trial of acetate in preterm neonates receiving parenteral
nutrition Arch Dis Child 1997 77 F12ndash15
24 yildizda D yapiciolu H yilmaz Hl Sertdemir y Correlation of
simultaneously obtained capillary venous and arterial blood gases
of patients in a paediatric intensive care unit Arch Dis Child 2004
89 176ndash180
25 aliwalas ll noble l nesbitt K et al agreement of carbon
dioxide levels measured by arterial transcutaneous and end tidal
methods in preterm infants 28 weeks gestation J Perinatol 2005
25 26ndash29
26 Hagerty JJ Kleinman me Zurakowski D et al accuracy of a new
low-flow sidestream capnography technology in newborns a pilot
study J Perinatol 2002 22 219ndash225
paeDiatRiCS anD CHilD HealtH 184 17
27 poets CF Wilken m Seidenberg J Southall Dp von der Hardt H
Reliability of a pulse oximeter in the detection of hyperoxemia
J Pediatr 1993 122 87ndash90
Practice points
bull a stable extracellular pH is important for optimal cellular
functioning
bull abnormalities in acidndashbase balance are regulated by buffer
systems and the respiratory and renal tract
bull maintaining a stable pH is challenging for newborn babies
due to their high rates of acid production and immature
regulatory mechanisms
bull arterial or capillary blood gases provide an effective way to
monitor acidndashbase balance in newborns
bull Blood gases should be analysed in a structured manner
assessing pH and then respiratory and metabolic components
bull the treatment of acidndashbase abnormalities should be directed
at the underlying problem not merely at correcting pH
7 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Recognition and management of neonatal seizuresmalcolm levene
AbstractSeizures are the most common major manifestation of central nervous
system dysfunction in the newborn there are many causes but perina-
tal asphyxia and haemorrhagicinfarction lesions account for about 75
there is now considerable evidence that frequent but short seizures in
the neonate affect subsequent neurodevelopmental outcome Studies
using eeg or modified continuous tracing of eeg activity (aeeg or CFm)
have shown that there is often electroconvulsive dissociation this re-
fers to poor correlation between electrical seizures and clinical seizures
Commonly used anticonvulsants appear to increase electroconvulsive
dissociation effective management of neonatal seizures has proved very
disappointing and less than 50 of seizures are abolished by first-line
anticonvulsant medication (phenobarbitone or phenytoin) Drugs such
as midazolam and lidocaine may further reduce seizures but require
more evaluation the challenge is to assess new and more effective anti-
convulsants which are themselves associated with little neurotoxicity
Keywords antiepileptic drugs eeg neonatal seizures neurodegeneration
Convulsions are the most common major neurological sign seen in newborn infants and their incidence estimated from large population studies is 26 per 1000 live births1 Premature infants are over four times more likely to have convulsions than full-term infants12 Neonatal status epilepticus (continuous seizure activity lasting 30 min or more) diagnosed clinically is rare and accounts for only 5 of infants with seizures1 although this is now recognized more frequently as the result of continuous EEG monitoring3
Neonatal convulsions are described as presenting in a num-ber of different ways and various seizure types can be seen in the same baby over a number of hours The frequencies of the various patterns of seizure activity are given in Table 1 In very premature babies and to a lesser extent in term infants minor movement abnormalities may be difficult to identify as subtle seizures These include lip smacking tongue thrusting mouth-ing pedalling type movements of the lower limbs or swimming movements of the arms Apnoea can be a common manifesta-tion of subtle seizures The signs can be protean and vary from baby to baby or even in the same baby Virtually any stereotypic
Malcolm Levene MD FMedSc FRCPCH FRCH is Professor and Head of
Department of Paediatrics and Child Health at University of Leeds Leeds
and Honorary Neonatologist at Leeds General Infirmary Leeds UK
paeDiatRiCS anD CHilD HealtH 184 178
movement may be a manifestation of a seizure disorder in the newborn
Aetiology
The more carefully the fitting baby is investigated the more likely it is that a cause for the seizures will be found A number of recent papers have described the aetiology of neonatal con-vulsions after extensive investigations14 Tekgul et al4 recently studied a consecutive group of full-term infants with evidence of neonatal convulsions (recognized both clinically and on EEG) and reported their outcome Table 2 summarizes these data as well as risk of moderate or severe disability for each causative factor Perinatal asphyxia is the commonest cause for convul-sions in term infants with haemorrhagic or ischaemic lesions also being common
Overall the prognosis for the group of term babies with con-vulsions was good 72 had a favourable outcome Where asphyxia (hypoxicndashischaemic insult) is the cause of neonatal convulsions the outcome is poor in 50 The prognosis for neonatal convulsions when they were due to arterial or cere-brovenous infarction or intracranial haemorrhage was generally good Individually inborn errors are a very rare cause of neo-natal convulsions but in view of the treatable nature of some of these it is essential that these be considered and investigated appropriately5
Patterns of seizure activity in the newborn
Movement pattern Frequency ()
Clonic 50
tonic 20
Subtle 10ndash35 depending on maturity
myoclonic 5
Table 1
Cause incidence and outcome of neonatal convulsions in term infants14
Aetiological factor Incidence () Poor outcome ()
asphyxia 38ndash40 50
Cerebral arteriovenous
infarction
20 0
intracranial haemorrhage 12ndash20 13
Congenital cerebral anomaly 5ndash10 100
Hypoglycaemiahypocalcaemia 3ndash19
infection 3ndash20
inborn error of metabolism 1
unknown cause 10ndash13 0
Refers to moderate and severe neurodevelopmental abnormalitynumbers too small to make meaningful predictions
Table 2
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Controversies in the clinical management of neonatal seizures
In recent years we have learnt much more about the neurobi-ology of seizures and their effect on the developing brain The neonatal brain is in a neurophysiologically hyperexcitable state compared to the more mature brain and therefore is more prone to seizure activity This is due largely to a relative excess of GABA neuroreceptors GABA receptors are usually inhibitory but in the immature brain they have a paradoxically excitatory effect This changes at about term in primates and with progressive develop-ment they adopt a neuroinhibitory role6
The propensity to seizures in the neonatal brain makes resolv-ing the balance of risks between continuing seizure activity on the one hand against potentially adverse effects of therapy on the other a very important equation Added to this is the problem of accurately diagnosing neonatal seizures and whether commonly used anticonvulsants are successful in controlling them
These conundrums can be posed as a series of challenging questions which are discussed below
Do neonatal convulsions cause brain injuryConvulsions are a sign of neurological compromise and may indi-cate significant underlying structural brain damage or biochemi-cal disturbance which may cause further brain damage in its own right There has been considerable debate about the scale of the disability that convulsions cause the immature brain over and above that due to the underlying cause Most of our knowledge comes from studies in rodents and these have provided some tentative answers to this question
Seizures in the mature brain lead to neuronal necrosis but studies in very young rat pups whose brain development is somewhat similar to full-term infants have shown that a series of five brief seizures on five successive days does not cause struc-tural neuronal damage but does produce morphological changes in hippocampal neurones and worryingly deficits in the rat learning and visual spatial memory function in adolescent and adult life7 A single prolonged neonatal convulsion in similarly immature rats does not produce any functional effects8 Others have shown that following priming of the neonatal rat brain by short seizures as described above a further insult comprising induction of status epilepticus in the same rats at an older age causes neuronal necrosis9 This has been referred to as the lsquotwo hit hypothesisrsquo10
A more specific question is does seizure activity in an already significantly compromised brain cause additional neuropathol-ogy Wirrell et al11 studied a series of immature rat pups with the induction of an hypoxicndashischaemic (asphyxial) insult fol-lowed by either chemically-induced fits or a control sham pro-cedure In the more severely asphyxiated animals the degree of brain damage was increased significantly in those that had the additional burden of induced seizures
In summary these studies show that the immature brain is more resistant to short frequent post-seizure damage than the mature brain but despite resulting in no loss of neuronal numbers the function of the brain is permanently affected in later life In the asphyxiated brain seizures appear to have an additional adverse effect on brain damage Furthermore the immature brain that has been lsquoprimedrsquo by early seizures is more
paeDiatRiCS anD CHilD HealtH 184 179
vulnerable to status epilepticus later in life It would appear from these data that frequent seizures in the human infant should be stopped and this begs the question as to whether currently used anticonvulsants effectively control neonatal seizures
Can we rely on clinical versus EEG diagnosis of neonatal convulsionsTraditionally the diagnosis of neonatal convulsions has been made by observation and description of the frequency of abnor-mal movements EEG has been technically difficult in the hostile electrical activity of a neonatal intensive care environment and considerable expertise is required for analysis of the trace It is usually not practical to undertake traditional EEG recordings at the time the baby shows abnormal movements More recently various technological developments have allowed more direct investigation of neuronal electrical activity by either video-EEG or compressed recording of the amplitude integrated EEG (aEEG or CFM)
Rennie et al3 at Kingrsquos College Hospital London have under-taken extensive evaluation of video-EEG and have found that this technique detects many convulsions not recognized by a single channel aEEG or CFM trace Of 19 infants with evidence of convulsions on EEG only four were recognized on CFM but this may have been due to the observersrsquo lack of experi-ence with this technique In other centres that have developed appropriate expertise aEEG or CFM has proved more sensitive to the detection of seizures Video-EEG studies have also shown that many movements interpreted by experienced clinicians to be seizures are not associated with abnormal cortical activity Conversely many electrical seizures are not associated with abnormal movements This is referred to as electroconvulsive dissociation
In summary clinical observation alone to detect the fitting baby is unreliable in that it may either over-detect seizure activ-ity which is not present on EEG or under-detect clinical seizures in infants with EEG-proven convulsions The decision as to which babies to treat with antiepileptic drugs therefore becomes somewhat arbitrary
Do anticonvulsants stop neonatal seizuresAlthough neonatal seizures are common there are few random-ized controlled trials assessing the benefits of antiepileptic drugs (AEDs) in the treatment of this condition Phenobarbitone is the most widely used first-line AED and in an Australasian study 95 of neonatologists and paediatric neurologists used this drug as first-line management12 The most commonly used loading dosage is 20 mgkg but regimens of up to 40 mgkg have been recommended (Table 3)13 Four trials have evaluated the effect of phenobarbitone in abolishing neonatal seizures Two of these studies used EEG to monitor response to the drug1415 and one compared phenobarbitone with phenytoin15 In the latter study seizures were completely controlled in only 43 of babies and in the group where phenytoin was the first drug used com-plete seizure control was achieved in 45 This study switched babies from their first AED to the other if complete control was not obtained on EEG monitoring after exposure to first-line therapy In babies who had been given phenobarbitone as first-line therapy seizure control was only achieved in 57 after phenytoin was added In those given phenytoin first complete
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Dosage regimens for first- second- and third-line anticonvulsants in the neonatal period
Loading dose Second loading dose if first
unsuccessfulMaintenance dose
phenobarbitone 20 mgkg by slow iv injection 10 mgkg iv 25ndash5 mgkg od
phenytoin 20 mgkg iv over 20 min not recommended
midazolam 150ndash200 μgkg iv infusion 1 μgkgmin iv infusion increasing to 5 μgkgmin
until favourable response
lidocaine 2 mgkg iv over 10 min 6 mgkgh for 6 h iv then 4 mgkgh for 12 h then
2 mgkgh for 12 h
lorazepam 005ndash01 mgkg by slow iv injection
Diazepam 03ndash04 mgkg iv over 3ndash5 min
lidocaine should not be used if the infant has previously been treated with phenytoin
Table 3
seizure control was achieved with the adding of phenobarbitone in 62
Boylan et al14 assessed the efficacy of phenobarbitone (20ndash40 mgkg iv over 20 min) in 14 babies monitored by video-EEG in only four was there complete abolition of seizures and in the other 10 electroconvulsive seizure activity increased whereas clinical evidence of seizures reduced This has been termed elec-troclinical dissociation and anticonvulsant drug use in the new-born appears to increase this feature They also showed that the babies least likely to respond to the first-line AED are those with the most abnormal background EEG
Two studies have evaluated the use of phenobarbitone in babies who had sustained significant asphyxial insult at birth Hall et al13 compared high-dose phenobarbitone (mean 39 mgkg) versus standard dose (27 mgkg) and reported fewer convul-sions and a significant reduction of severe disability or death in the high dose group (RR 030 CI 010ndash093) A recent study from India16 of babies with hypoxicndashischaemic encephalopathy ran-domized 25 babies to phenobarbitone (20 mgkg loading dose) and compared them with 20 control babies Only 2 of 25 (4) in the phenobarbitone group developed convulsions compared with 8 of 20 (40) in the control group (p = 001) Because of the specific enrolment criteria (asphyxial insult) neither of these studies is strictly comparable to the studies by Painter et al15 and Boylan et al14 whose intention was to assess the efficacy of first-line anticonvulsant therapy on convulsions of any cause diagnosed either clinically or by EEG
Other anticonvulsants used as second- and third-line drugs have been subject to few studies in the newborn Midazolam is administered as a bolus followed by continuous infusion A recent study17 has shown that in 10 of 13 neonates given intravenous midazolam for status epilepticus control of electri-cal seizures was achieved within the first hour of treatment having been previously shown to be refractory to phenobarbi-tone treatment Some of these babies required a second bolus infusion of midazolam to obtain control of all electrographic seizures
In some parts of Europe lidocaine is used as a third-line anti-convulsant Malingre et al18 evaluated 20 infants refractory to
paeDiatRiCS anD CHilD HealtH 184 180
both phenobarbitone and midazolam and who were then given lidocaine by continuous infusion Lidocaine was effective in abolishing electroconvulsive seizures diagnosed by aEEG in 76 of the treatment courses studied No babies developed cardiac arrhythmias a previously reported complication of lidocaine in older patients As a result of pharmacokinetic studies the dosage regimen has been modified (see Table 3)
In summary phenobarbitone is effective in seizure control in less than 50 of babies and even when combined with phe-nytoin the efficacy of these drugs together remains poor More worrying is the observation that phenobarbitone tends to reduce clinically evident seizures thereby giving the clinician a false sense of security whilst having little or no effect on the num-bers of electroconvulsive disorders This has been summarized appropriately as lsquoafter all these years we still love what doesnrsquot workrsquo19 Both midazolam and lidocaine infusions appear to be effective in abolishing severe seizures in some infants resistant to phenobarbitone Lidocaine should not be given to babies previ-ously exposed to phenytoin for fear of a synergistic adverse effect on cardiac rhythm
Do antiepileptic drugs cause brain damageA riskndashbenefit analysis is needed to evaluate the efficacy of anticonvulsants in stopping neonatal seizures which is poor with standard anticonvulsants as discussed above against the risk of administering the anticonvulsant drugs themselves Phenobarbitone has been reported to have adverse effects on the developing brain including inhibition of brain growth20 neuronal toxicity21 and adverse behavioural and cognitive effects into adult life when administered to young animals22 Phenytoin shows unpredictable plasma levels and potential cardiotoxicity
Recent studies have shown an effect of AED exposure on the developing brain by causing neurodegeneration23 Phenytoin administration to immature rat pups at doses which produce serum levels similar to those achieved in human neonates was associated with widespread neuronal death as a result of apop-tosis (programmed cell death) Phenobarbitone had a similar effect when a dosage regimen similar to 40 mgkg was used and
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
this effect was maximal in the more immature brain Diazepam and clonazepam also resulted in a similar effect Midazolam and lidocaine were not tested in this study The combination of phenobarbitone or phenytoin with diazepam had a particularly profound effect on neurodegeneration
In summary recent data suggest that the commonly used AEDs for neonatal convulsions may in themselves cause neuro-degeneration due to apoptosis with lasting effects on develop-ment Many babies with neonatal convulsions are treated with at least two AEDs and this may produce more severe adverse effects than the seizures themselves
Practical management of neonatal seizures
Assimilation of these data and formulation of a rational policy is difficult when faced with a fitting neonate on an intensive care unit and pressure on the medical staff to lsquodo somethingrsquo but it is important to accept that sometimes doing nothing is preferable to using potentially dangerous drugs in a situation which does not warrant such intervention Many babies who have normal interseizure neurological clinical findings and whose seizures are relatively brief and infrequent probably do not need anticon-vulsant medication A normal or near-normal background EEG trace should reassure the clinician that anticonvulsants can be withheld
Some causes of neonatal convulsions are treatable such as meningitis hypoglycaemia hypocalcaemia and inborn errors of metabolism and each baby should be rapidly and carefully investigated for cause of the convulsions
In some babies clinical assessment of seizures is difficult ie when the baby is very sick small or paralyzed Sometimes it may be difficult to assess the significance of certain movement pat-terns Under these circumstances an EEG may prove to be very helpful In many units EEG is not available out of hours and a simple aEEG or CFM is strongly advised Modern instruments are very simple to apply and prolonged or frequent seizures should be identified with only moderate training The printout can be faxed to a more senior doctor if there is doubt as to what is shown on the trace
The balance of knowledge now is that frequent seizures cause additional damage to the developing brain and that treatment to abolish the seizures is warranted Unfortunately there is little evidence that the majority of seizures can be effectively termi-nated by current standard therapy Furthermore it appears that the more abnormal the background EEG the more difficult it is to control the seizures Nevertheless a written protocol for the management of neonatal convulsions is required on each unit Phenobarbitone and phenytoin remain the mainstay of treat-ment although their effectiveness is disappointing There is little to suggest that midazolam is more effective than lidocaine as third-line therapy but lidocaine is precluded if phenytoin has been previously used
In view of the anxiety as to the neurodegenerative effects on the immature brain of most anticonvulsants used in the neonatal period (particularly when multiple drugs are used) it is prefer-able to use only one drug to maximum dosage before introduc-ing a second In addition the duration of anticonvulsants should be minimized and the drugs stopped at the earliest opportu-nity It is my practice to stop anticonvulsants prior to discharge
paeDiatRiCS anD CHilD HealtH 184 18
from hospital if the baby is neurologically normal on clinical examination
REFEREnCES
1 Ronen gm penney S andrews W the epidemiology of clinical
neonatal seizures in newfoundland a population-based study
J Pediatr 1999 134 71ndash75
2 lanska mJ lanska DJ Baumann RJ et al a population-based study
of neonatal seizures in Fayette County Kentucky Neurology 1995
45 724ndash732
3 Rennie Jm Chorley g Boylan gB et al non-expert use of the
cerebral function monitor for neonatal seizure detection Arch Dis
Child Fetal Neonatal Ed 2004 89 F37ndashF40
4 tekgul H gauvreau K Soul J et al the current etoliologic profile
and neurodevelopmental outcome of seizures in term newborn
infants Pediatrics 2006 117 1270ndash1280
5 Surtees R Wolf n treatable neonatal epilepsy Arch Dis Child 2007
92 659ndash661
6 Ben-ari y Holmes gl effects of seizures on developmental
processes in the immature brain Lancet Neurol 2006 5 1055ndash
1063
7 Holmes gl gairsa Jl Chevassus-au-louis n et al Consequences of
neonatal seizures in the rat morphological and behavioral effects
Ann Neurol 1998 44 845ndash857
8 Stafstrom Ce Chronopoulos a thurber S et al age-dependent
cognitive and behavioural deficits following kainic-acid inducing
seizures Epilepsia 1993 34 420ndash432
9 Schmid R tandon p Stafstrom Ce et al effects of neonatal seizures
on subsequent seizure-induced brain injury Neurology 1999 53
1754ndash1761
10 Hoffmann aF Zhao Q Holmes gl Cognitive impairment following
status epilepticus and recurrent seizures during early development
support for the ldquotwo-hit hypothesisrdquo Epilepsy Behav 2004 5
873ndash877
11 Wirrell eC armstrong ea osman lD et al prolonged seizures
exacerbate perinatal hypoxic-ischemic brain damage Pediatr Res
2001 50 445ndash454
12 Carmo KB Barr p Drug treatment of neonatal seizures by
neonatologists and paediatric neurologists J Paediatr Child Health
2005 41 313ndash316
13 Hall Rt Hall FK Daily DK High-dose phenobarbital therapy in term
newborn infants with severe perinatal asphyxia a randomized
prospective study with three-year follow-up J Pediatr 1998 132
345ndash348
14 Boylan gB Rennie Jm pressler Rm et al phenobarbitone neonatal
seizures and video-eeg Arch Dis Child Fetal Neonatal Ed 2002 86
F165ndash170
15 painter mJ Scher mS Stein aD et al phenobarbital compared with
phenytoin for the treatment of neonatal seizures N Engl J Med
1999 341 485ndash489
16 Singh D Kumar p narang a a randomized controlled trial of
phenobarbital in neonates with hypoxic ischemic encephalopathy
J Matern Fetal Neonatal Med 2005 18 391ndash395
17 Castro Conde JR Borges H Domenech martinez e et al midazolam
in neonatal seizures with no response to phenobarbital Neurology
2005 64 876ndash879
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
18 malingre mm Van Rooij lgm Rademaker Cma et al Development
of an optimal lidocaine infusion strategy for neonatal seizures Eur
J Pediatr 2006 165 598ndash604
19 Sankar R painter mJ neonatal seizures after all these years we still
love what doesnrsquot work Neurology 2005 64 776ndash777
20 Diaz J Schain J Bailey Bg phenobarbital-induced brain growth
retardation in artificially reared rat pups Biol Neonate 1977 32 77ndash82
21 mattson RH phenobarbital toxicity in levy RH Dreifuss Fe
mattson RH et al eds antiepipeptic Drugs 3rd edn new york
Raven 1985 p 341ndash355
22 mikati ma Holmes gl Chronopoulos a et al phenobarbital
modifies seizure-related brain injury in the developing brain Ann
Neurol 1994 36 425ndash453
23 Bittigau p Sifringer m genz K et al antiepileptic drugs and
apoptotic neurodegeneration in the developing brain Proc Natl
Acad Sci U S A 2002 99 15089ndash15094
paeDiatRiCS anD CHilD HealtH 184 182
Practice points
bull the clinician needs to be aware that almost any repetitive
stereotype movement pattern can be a manifestation of
neonatal seizures
bull eeg is important in defining neonatal seizures
bull Frequent short-lived seizures have been shown to cause long-
term neurodevelopmental problems
bull Conventional anticonvulsant medication is ineffective in
abolishing neonatal seizures in greater than 50 of cases
bull there is evidence that exposure of the neonatal brain to
multiple anticonvulsants causes neuronal death
bull Future research is needed to evaluate more effective
anticonvulsants for treating this condition
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
Emotional support for families of sick neonatesMarina nicolaou
cristine Glazebrook
AbstractParents of sick neonates experience high levels of stress anxiety and
depression Most interventions with families of sick infants have focused
on fostering the motherndashinfant relationship through the provision of
information about infant developmental needs or through increased
motherndashinfant contact Many of these studies have reported improved
maternal well-being though there are some concerns about the scope
and practicality of large-scale interventions The few studies to have
prioritized emotional support for parents of sick neonates have pro-
duced encouraging results even interventions requiring relatively few re-
sources such as telephone support parent-to-parent support and group
support have been associated with reduced psychological morbidity for
parents The needs of parents can change throughout their infantrsquos hos-
pitalization and not all want or benefit from the provision of additional
support Thus neonatal intensive care units should aim to provide a
varied flexible and sustainable programme of support options Further
research should focus on the needs of fathers
Keywords mental health neonatal intensive care parents
The admission of an infant to neonatal care is acknowledged to be a source of considerable distress for families This review aims to explore evidence for the psychological impact on families of having an infant in neonatal intensive care and to identify evi-dence for the effectiveness of interventions to promote parental well-being It will conclude with recommendations for strategies to support parents of vulnerable infants and suggestions for fur-ther research
Psychological impact of neonatal care for parents
The majority of research examining the effect on parents of having a sick neonate has focused on families of premature or low birthweight infants Such research has found that parents with a sick neonate exhibit high levels of stress compared to normative samples and to parents of healthy full-term infants1 Singer et al2 examined the stress experienced by mothers of high-risk very low birthweight (VLBW) low-risk VLBW and term
Marina Nicolaou MPhil is a Teaching Assistant at the School of
Community Health Sciences University of Nottingham Nottingham UK
Cristine Glazebrook PhD is a Professor of Health Psychology at the School
of Community Health Sciences University of Nottingham Nottingham UK
PaeDiaTrics anD cHilD HealTH 184 196
infants Several self-report measures were used including the Brief Symptom Inventory the Parenting Stress Index (PSI) the Impact on Family Scale and the Family Inventory of Life Events and Changes (FILE) Mothers of VLBW infants had more psycho-logical distress at 1 month compared to mothers of term infants Mothers of high-risk VLBW infants also reported high psycho-logical distress at 2 years and high levels of parenting stress at 3 years Mothers have also been found to have higher stress levels compared to fathers Shaw et al3 examined the prevalence of acute stress disorder (ASD) in 40 parents whose infants were in the neonatal intensive care unit (NICU) Nearly half of the moth-ers (44) met the criteria for ASD although none of the fathers did Furthermore the severity of the symptoms (measured by the number of concurrent symptoms) was greater for the moth-ers than for the fathers3 The reasons behind this difference have been widely speculated with some believing that it is due to the mothersrsquo greater psychological involvement with the infant as evidenced by their general greater vulnerability to postpartum psychological disorder It could also reflect gender differences in coping style
Having an infant who requires intensive medical care repre-sents a significant emotional burden for families Not only is there extreme anxiety surrounding the infantrsquos health and distress for the childrsquos suffering there is also the unfamiliar and intimidating environment of the NICU to adjust to Hopper in her review of the literature identified sources of stress for parents of sick neo-nates as falling into three areas4 Situational factors included the severity of the infantrsquos illness and how parents adapted to the life crisis of having a sick infant Personal factors involved parental emotions about their roles and the instrumental and informa-tional support which were available to them The third area was classified as environmental sources of stress and included the environment of the NICU and the relationship between parents and members of staff This relationship has been examined by several studies in the nursing literature nurses are seen as ide-ally placed to provide the necessary support and information to parents with sick neonates However whilst some studies have shown that supportive and helpful hospital staff can have a posi-tive effect on parents other studies have highlighted the prob-lems and difficulties which can manifest It has been shown that parents and nurses often have very different ideas about issues eg the necessary skills and competencies needed in an NICU or the characteristics that make a lsquogood motherrsquo
Research has shown that there may be a relationship between high levels of parental stress and an increased likelihood of depression5 Postpartum depression is a psychiatric illness which appears in 10ndash15 of postpartum women Its reported preva-lence rates however have ranged from less than 10 up to 306 depending on the instruments used the population exam-ined and the timing of the research Several factors have been found to be associated with postpartum depression including poor social support and infant-related stressors6 Evidence indi-cates that postnatal depression may be underreported and this is of concern since the mental and psychological health of the mother can affect her relationship with her infant and thus the infantrsquos cognitive and emotional development5 Depressed moth-ers appear to look touch and talk to their infants less frequently and also appear to show fewer positive and more negative faces7 The vocalizations of mothers suffering with depression have also
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
been found to be less effective at promoting cognitive growth and learning in infants8
If researchers are interested in finding ways of providing sup-port for families of sick neonates then they must listen to what such families perceive their needs to be in order to avoid increas-ing anxiety and distress Furthermore the provision of appropri-ate support be it emotional informational or social will enhance parental coping abilities increase self-esteem and reduce anxiety It should be noted though that the research conducted around these issues has often taken lsquosupport needsrsquo as being synony-mous with lsquoinformation needsrsquo Such studies have examined the type the amount and quality of information that parents receive and perceive themselves as needing but have not explored in equal depth the perceived emotional support needs of families who have a sick infant In addition the needs of parents may change throughout their infantrsquos illness Ward examined the per-ceived needs of 52 parents of infants in an NICU9 Parents rated the needs of their hospitalized infant as most important along with the need to be reassured Interestingly they ranked their support needs as least important This research was conducted during the first week of the infantsrsquo hospitalization however which would explain the preoccupation of the parents with the infantrsquos health These results demonstrate that if researchers want to find ways of providing emotional support to parents of sick neonates they must be prepared not only to listen to parents but also to be flexible enough to satisfy the parentsrsquo changing needs and expectations
Interventions aimed at supporting parents
Most interventions that been evaluated in controlled studies have focused on supporting the motherndashinfant relationship and provid-ing information on infant development Many of these interven-tions have included the aim of improving the parental emotional state and thus psychological outcomes such as stress or anxi-ety have been assessed However few studies appear to include fathers This means that strategies implemented to provide emo-tional support to families of sick neonates are often derived from interventions tailored for mothers even though fathers may have different emotional needs
A wide range of interventions with mothers and infants has been evaluated in the NICU Increasing motherndashinfant contact through kangaroo care has been found to reduce maternal anxiety1011 and educational programmes delivered to fami-lies in the NICU have also been associated with reduced emo-tional difficulties in parents12ndash14 Kaaresen and colleagues implemented an intervention which consisted of eight sessions before discharge and four home visits all by trained nurses The sample included 71 premature infants in the intervention group 69 premature infants in the control group and 74 infants in the full-term control group The randomized controlled trial found that the intervention reduced parenting stress in both mothers and fathers of premature infants compared to controls to a level equivalent to parents in the term control group13 At 6 months corrected age mothers of preterm infants who had not received the intervention had total PSI scores which were 17 points higher than the mothers of infants born at term (an effect size of 057) A similar study evaluated the efficacy of an educationalndashbehavioural programmendashCreating Opportunities for
PaeDiaTrics anD cHilD HealTH 184 19
Parent Empowerment (COPE) ndash through a randomized controlled trial with 260 families of premature infants14 COPE was a four-phase educationalndashbehavioural programme which began as early as 2ndash4 d after mothers had given birth and continued until 1 week after discharge from the NICU The programme consisted of audiotaped and written infant behaviour information along with photographs which focused on common behaviours and characteristics of premature infants It also included various par-ent activities in the form of a four-phase workbook which aimed to assist mothers in the implementation of the experimental infor-mation COPE was found significantly to reduce maternal stress in the NICU as well as maternal anxiety and depressive symptoms after hospitalization In contrast a cluster randomized trial of a parenting intervention delivered to mothers of very premature infants from soon after birth showed no benefits for parenting stress1 The authors hypothesized that the intervention had not been of sufficient intensity particularly in the weeks surrounding discharge Neonatal care presents a significant barrier to parent-ing in the early weeks following a very preterm birth and so inter-ventions which focus on the developmental needs of infants and the parentndashchild relationship should particularly aim to support parents as they take on the parenting role There was also concern that the intervention had failed to reach those most at risk
Since large-scale projects can be costly to implement and may often fail to reach the families in most need it may be wiser to focus on intervention programmes which are more practical and easier to implement within a neonatal care setting Research has shown that even interventions which are based on one-off meet-ings with parents of sick neonates can be effective Jotzo and Poets examined the effect of an intervention programme aimed at reducing the severity of traumatic responses as a result of giv-ing birth prematurely15 Their programme consisted of a one-off intervention meeting along with additional psychological help throughout the hospitalization of the infant The meeting cov-ered a variety of issues including a reconstruction of the events shortly before and after the infantrsquos birth relaxation techniques discussion of coping strategies available resources and social support and support during emotional outbursts The measures used included the Impact of Event Scale (IES) and the Peritrau-matic Dissociative Experience Questionnaire At discharge the mothers who received the intervention were found to have a significantly lower traumatic impact as a result of premature birth Furthermore fewer mothers in the intervention group showed symptoms of clinically significant psychological trauma at discharge compared to mothers in the control group (36 vs 76)15 The lsquoParents Circle Programrsquo is another intervention with a similar structure16 This consisted of a 90 min session for parents with the aim of enhancing the developing relationship between parents and infants and to offer parents support A total of 104 parents (59 mothers and 45 fathers) and 44 members of hospital staff were asked to evaluate the programme and their results were analysed using content analysis Families reported gaining perspective on their situation feeling supported becom-ing aware of cues and optimizing interactions and becoming aware of available resources Parents and staff alike felt that participating in the intervention helped parents overcome the difficulties associated with the early time of their infantrsquos hos-pitalization Additional studies have also found positive results with fairly minimal interventions including discussion groups
7 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
in the NICU music during kangaroo care and pairing mothers of sick neonates with trained mothers who had been through similar experiences
Parent support programmes
Parent support programmes (PSPs) which are based in NICUs can provide parents with the opportunity to talk to parents who have been in similar situations and also to discuss their emo-tions with professionals who can help them cope with their situa-tion111718 The parent-to-parent support programme for mothers of preterm infants evaluated by Preyde and Ardal included edu-cational parental support group meetings and individual par-ent-to-parent support (primarily telephone support)19 Measures used included the Parental Stressor Scale NICU the State and the Trait Anxiety Inventories and the Beck Depression Inven-tory After 4 months of participation mothers in the intervention group reported lower levels of stress state anxiety and depres-sion compared to control group mothers The authors speculated however that the participants who were able to meet face to face with other parents were those who benefited the most Hurst conducted a comprehensive survey of an NICU-based PSP This PSP was provided in a variety of formats including a weekly parent support group hospital visitation and 24-h telephone sup-port20 Of the 477 participants 303 families used the PSP dur-ing a 2-year evaluation period with 78 using only one form of support and 18 using two forms Of a sub-sample of 48 parents asked to complete an evaluation of the PSP 92 stated that they would recommend such a programme to other parents Furthermore the majority of parents felt that it made them feel supported and helped them deal with their emotions20 This is an indication that such programmes can be very successful in sup-porting parents throughout their infantrsquos hospitalization It also shows that it can be beneficial to give parents several options and formats when it comes to such support services It is impor-tant to consider though that both the Hurst and the Preyde and Ardal studies found that some participants did not find the sup-port programmes helpful even reporting that they had caused them increased stress and anxiety Therefore it should not be assumed that support programmes will suit every individual and will provide the required support for all parents1920 NICUs need to be flexible enough to provide parents with a range of forms of support to choose from
The increased understanding of the strains that parents of sick neonates have to deal with has also led to efforts to improve customary practices in NICUs Family-centred care focuses on infants and their needs and attempts to redefine the relationship between parents and caregivers These practices strive to provide parents with support during their infantrsquos illness by focusing on freely sharing information and on the collaboration between parents and hospital staff Family-centred care has been found to be associated with several beneficial outcomes including improved parental satisfaction increased parental comfort staff satisfaction and decreased parental stress18 Research is already examining these practices and questioning how these can be improved further Such research reflects the increasing effort focused on lsquohumanizingrsquo the environment in NICUs in order to make parents feel more comfortable about spending time with their infants
PaeDiaTrics anD cHilD HealTH 184 19
Conclusion
Surprisingly few interventions have prioritized the provision of emotional support for parents of sick neonates or accounted for the changing needs and wishes of parents over the course of their infantrsquos care Large-scale supportive education-based inter-ventions have been shown to be effective in reducing parental distress However the feasibility and sustainability of such pro-grammes should also be considered Programmes which require significant additional resources can be expensive and there are also issues of training and quality control Interventions which require significant input from parents may also place additional burdens on families making them potentially less accessible to those most at risk Arguably the aim should be to explore ways of providing acceptable and effective informational support which could be complemented by emotional support from health professionals and from other parents in the unit Increasingly studies are exploring the use of computers and multimedia as an engaging flexible and cost-effective method of targeting indi-vidual needs and providing support and information Such com-puter-based and interactive multimedia interventions have been found to be successful with a range of patient groups and could therefore be examined as a complementary method of providing informational support to families with sick neonates
REfEREnCEs
1 Glazebrook c Marlow n israel c et al randomised trial of a
parenting intervention during neonatal intensive care Arch Dis Child
Fetal Neonatal Ed 2007 92 F438ndash443
2 singer lT salvator a Guo s collin M lilien l Baley J Maternal
psychological distress and parenting stress after the birth of a very
low-birth-weight infant JAMA 1999 281 799ndash805
3 shaw rJ Deblois T ikuta l Ginzburg K Fleisher B Koopman c
acute stress disorder among parents of infants in the neonatal
intensive care nursery Psychosomatics 2006 47 206ndash212
4 Hopper a sources of stress for parents of a sick neonate a
literature review Pediatr Nurs 2000 30 29ndash32
5 Davis l edwards H Mohay H wollin J The impact of very
premature birth on the psychological health of mothers Early Hum
Dev 2003 73 61ndash70
6 Bernazzani O saucier J-F David H Borgeat F Psychosocial
predictors of depressive symptomatology level in postpartum
women J Affect Disord 1997 46 39ndash49
7 Field T infants of depressed mothers Infant Behav Dev 1995 18
1ndash13
8 Kaplan Ps Bachorowski J-a Zarlengo-strouse P child-directed
speech produced by mothers with symptoms of depression fails
to promote associative learning in 4-month-old infants Child Dev
1999 70 560ndash570
9 ward K Perceived needs of parents of critically ill infants in
a neonatal intensive care unit (nicU) Pediatr Nurs 2001 27
281ndash286
10 lai Hl chen cJ Peng Tc et al randomized controlled trial of music
during kangaroo care on maternal state anxiety and preterm infantsrsquo
responses Int J Nurs Stud 2006 43 139ndash146
8 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
11 Tallandini Ma scalembra c Kangaroo mother care and mother-
premature infant dyadic interaction Infant Ment Health J 2006 27
251ndash275
12 Ohgi s Fukuda M akiyama T Gima H effect of an early intervention
programme on low birthweight infants with cerebral injuries
J Paediatr Child Health 2004 40 689ndash695
13 Kaaresen Pi ronning Ja Ulvund se Dahl lB a randomized
controlled trial of the effectiveness of an early-intervention program
in reducing parenting stress after preterm birth Pediatrics 2006
118 e9ndash19
14 Melnyk BM Feinstein nF alpert-Gillis l et al reducing premature
infantsrsquo length of stay and improving parentsrsquo mental health
outcomes with the creating opportunities for parent empowerment
(cOPe) neonatal intensive care unit program a randomized
controlled trial Pediatrics 2006 118 e1414ndash1427
15 Jotzo M Poets cF Helping parents cope with the trauma of
premature birth an evaluation of a trauma-preventive psychological
intervention Pediatrics 2005 115 915ndash919
16 Pearson J andersen K evaluation of a program to promote positive
parenting in the neonatal intensive care unit Neonatal Netw 2001
20 43ndash48
17 roman l lindsay J Boger r et al Parent-to-parent support
initiated in the neonatal intensive care unit Res Nurs Health 1995
18 385ndash394
18 Meyer ec coll cTG lester BM Boukydis cFZ McDonough sM Oh w
Family-based intervention improves maternal psychological well-
being and feeding interaction of preterm infants Pediatrics 1994
93 241ndash246
PaeDiaTrics anD cHilD HealTH 184 19
19 Preyde M ardal F effectiveness of a parent ldquobuddyrdquo program for
mothers of very preterm infants in a neonatal intensive care unit
CMAJ 2003 168 969ndash973
20 Hurst i One size does not fit all Parentsrsquo evaluations of a support
program in a newborn intensive care nursery J Perinat Neonatal
Nurs 2006 20 252ndash261
Practice points
bull Parents of sick neonates experience significant distress and
exhibit higher levels of stress anxiety and depression than
parents of healthy infants
bull educational support emotional support and increased
motherndashinfant contact have been shown to promote maternal
well-being
bull emotional support for fathers has been largely neglected in
the research literature
bull Parents benefit from a choice of supportive facilities which
could include face-to-face sessions with health professionals
telephone support hospital visitation parent-to-parent
support and unit-based group support meetings
bull Parentsrsquo support needs can change during their infantrsquos
hospitalization and not all parents want or benefit from the
provision of additional information and emotional support in
the neonatal unit
9 copy 2008 elsevier ltd all rights reserved
Personal Practice
When should enteral feeds be started in preterm infantsnicholas D embleton
AbstractPaediatricians are regularly faced with the question of when best to start
enteral feeds in preterm infants this is important as longer term out-
come may be compromised by sub-optimal nutrition in early life clinical
factors that may affect the decision to start and the risk and benefits
are discussed
Keywords breast milk feeding nutrition parenteral nutrition
Key points in the history
Alice is lsquonutritionally vulnerablersquo and whilst this may not be immediately apparent it will affect her long term outcome Her energy stores are extremely limited and consist primarily of pro-tein She has less than 5 fat and little energy associated with stored glycogen She is losing about 1 gkgd protein equivalent so she needs at least that and a minimum of 50ndash60 kcalkg of energy just to maintain the status quo let alone grow
Her weight is on the 25th centile Review of any antenatal his-tory may reveal whether fetal growth was normal Fetal growth retardation can occur with a weight greater than 10th centile The presence of antenatal absent or reversed end diastolic flow in the umbilical artery indicates poor gut blood flow This increases the risk of necrotizing enterocolitis (NEC) and might suggest a more cautious approach to starting feeds1
She has no important cardiovascular problems but if she were hypotensive gut blood flow may be low There is no umbilical
Nicholas D Embleton BSC (Hons) MBBS (Hons) MD FRCPCH is Consultant in
Neonatal Medicine at Newcastle Neonatal Service Royal Victoria
Infirmary Newcastle upon Tyne NE1 4LP UK
Should you start feeds at a day of age
alice was born following spontaneous labour at 30 weeksrsquo
gestation she weighed 1300 g and is now 18 h old she was
briefly ventilated and then extubated to continuous positive
airway pressure 12 h ago in 35 oxygen she has had caffeine
citrate but still has intermittent episodes of self-correcting
apnoea she was commenced on iv 10 dextrose but this was
replaced by a parenteral amino acid solution (referred to as
lsquotPnrsquo) along with intralipid at 0900 this morning serum glucose
is 11 mmoll and blood pressure is 42 systolic
PaeDiatrics anD cHilD HealtH 184 20
arterial catheter in situ but there is no good evidence that this should delay the decision to start feeds Her glucose is high but this is quite common in a baby like this Could this be a sign of sepsis Caffeine does not affect the incidence of NEC2 The great-est risk factor for NEC in this case is prematurity
What else might be found on examination
Up until 24 h ago she was swallowing large amounts of amniotic fluid What will have changed since then
General examination should confirm peripheral perfusion lsquogestaltrsquo view (does she look lsquowellrsquo) and cardiovascular status lsquoBowel soundsrsquo are not usually helpful
The most important variable likely to affect gut perfusion is the arterial duct Precordial lsquoheaversquo and a loud murmur are sug-gestive but it is possible to have a significant ductal shunt in a baby with a normal examination Cardiac ultrasound will con-firm this diagnosis It might be better to treat a large shunt first with indometacin and to delay starting feeds for a further 24 h
It is not possible to assess gut perfusion clinically but normal perfusion elsewhere (adequate urine output usually indicates adequate renal perfusion) would be reassuring Most preterm babies have a few abdominal lsquoloopsrsquo visible but a distended abdomen with many palpable loops suggests ileus This might be secondary to sepsis or poor gut blood flow Preterm babies do not pass much meconium in the first 24ndash48 h
Balance of risks between starting and withholding feeds
Alice requires 35ndash4 gkgd of protein and 120 kcalkgd to grow3 This will initially be provided parenterally Delaying feeds increases the risk of gut villous atrophy and prolongs the need for lsquototal parenteral nutrition (TPN)rsquo TPN requires intravenous access and so increases the risk of sepsis and when prolonged use is required combined with the lack of enteral feeding may result in hepatic impairment
Delaying feeds may allow a gut that has been chronically under-perfused to re-establish more normal perfusion although normal gut endocrine function digestive enzyme upregulation and motility require a source of intraluminal nutrients1 A recent study suggested benefit from delaying the introduction of feeds4 but methodologi-cal problems exist5 Although a Cochrane meta-analysis suggested no benefit only two studies were included6 A large UK-based trial is examining the effect of early or late feeding in preterm infants who were born growth retarded following identification of antena-tal absent or reversed end diastolic flow in the umbilical artery7
When starting feeds what volume should be used
There are no good data to guide this decision We start with 24 mlkg (1 mlkgh) and then increase by this amount each day Most babies achieve full enteral feeds (ge150 mlkgd) by a week of age Feeding guidelines improve the outcome8 Measure-ment or assessment of gastric aspirates is not consistently useful in predicting subsequent feeding intolerance or development of NEC Aspirate volumes equivalent to or sometimes greater than the amount given in the preceding 1ndash2 h are usually normal Most aspirates have a greenish colour Thick bloody or intensely bile-stained aspirates require detailed assessment
0 copy 2008 elsevier ltd all rights reserved
Personal Practice
What else affects decisions and outcome
Feeding success is affected by sepsis and NEC Scrupulous atten-tion should be paid to hand washing and intravenous access and blood sampling should be minimized There is no good evidence to support the routine use of pro-kinetic agents or H2 blockers
The most important clinical intervention affecting the occur-rence of NEC is the use of breast milk9 All efforts should be directed at persuading parents of the benefits and supporting the process Some clinicians delay starting feeds for a further 24 h whilst expressed breast milk becomes available Donor breast milk might be equally efficacious10
RefeRenceS
1 Dorling J Kempley s leaf a Feeding growth restricted preterm
infants with abnormal antenatal Doppler results Arch Dis Child Fetal
Neonatal Ed 2005 90 F359ndash363
2 schmidt B roberts rs Davis P et al caffeine therapy for apnea of
prematurity N Engl J Med 2006 354 2112ndash2121
PaeDiatrics anD cHilD HealtH 184 20
3 embleton nD Pang n cooke rJ Postnatal malnutrition and growth
retardation an inevitable consequence of current recommendations
in preterm infants Pediatrics 2001 107 270ndash273
4 Berseth cl Bisquera Ja Paje VU Prolonging small feeding volumes
early in life decreases the incidence of necrotizing enterocolitis in
very low birth weight infants Pediatrics 2003 111 529ndash534
5 Menon G Boyle eM embleton nD et al introduction of enteral
feeds in preterm infants Pediatrics 2004 114 327ndash328
6 Kennedy Ka tyson Je chamnanvanikij s early versus delayed
initiation of progressive enteral feedings for parenterally fed low
birth weight or preterm infants Cochrane Database Syst Rev 2000
cD001970
7 wwwnpeuoxacukadept
8 Patole sK de Klerk n impact of standardised feeding regimens on
incidence of neonatal necrotising enterocolitis a systematic review
and meta-analysis of observational studies Arch Dis Child Fetal
Neonatal Ed 2005 90 F147ndash151
9 lucas a cole tJ Breast milk and neonatal necrotising enterocolitis
Lancet 1990 336 1519ndash1523
10 Boyd ca Quigley Ma Brocklehurst P Donor breast milk versus
infant formula for preterm infants systematic review and meta-
analysis Arch Dis Child Fetal Neonatal Ed 2007 92 F169ndash175
1 copy 2008 elsevier ltd all rights reserved
self-assessment
Case 1A term male infant born to consanguineous parents is assessed at 24 h of age due to poor feeding profuse yellow watery diar-rhoea and irritability He weighed 32 kg at birth and delivery was uneventful There was no polyhydramnios He has been breastfed since birth On examination he is pale with a non-tender but distended abdomen and reduced bowel sounds His weight is 275 kg and he looks dehydrated Examination is otherwise normal
Initial investigations (normal values in parentheses) showed
sodium 149 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 65 mmollitre (25ndash75)
creatinine 147 μmollitre (40ndash110)
chloride 119 mmollitre (95ndash105)
haemoglobin 172 gdl (140ndash200)
White blood cell count 80 times 109litre (100ndash260)
Platelet count 302 times 109litre (150ndash400)
arterial blood gas
ph 720 (730ndash745)
PcO2 23 kPa (46ndash60)
Bicarbonate 68 mmollitre (220ndash260)
Base excess minus186 mmollitre (minus20 to +20)
lactate 59 mmollitre (06ndash24)
An abdominal X-ray shows distended bowel loops with no intramural thickening or pneumoperitoneum (Figure 1)
He was given nil by mouth and received intravenous fluids and antibiotics His dehydration improved but the metabolic acidosis and diarrhoea persisted despite receiving no enteral feeds and the commencement of total parenteral nutrition Blood and stool cultures were negative
1 Which of the following best describes these results Choose ONE answer ONLY from the followingA Hypernatraemia hyperchloraemic metabolic acidosis
with increased anion gapB Hypernatraemia hyperchloraemic metabolic acidosis
with normal anion gap
Manish Sadarangani BM BCh MA MRCPCH is Clinical Research Fellow
at the Department of Paediatrics University of Oxford Centre for
Clinical Vaccinology and Tropical Medicine Churchill Hospital
Oxford OX3 7LJ UK
Shabna Rajapaksa MB BChir MA MRCPCH is Specialist Registrar in
Paediatrics at the Paediatric Intensive Care Unit John Radcliffe
Hospital Oxford OX3 9DU UK
Nicholas Mann MD FRCP FRCPCH DCH is Consultant Paediatrician at the
Department of Paediatrics Royal Berkshire Hospital Reading RG1
5AN UK
self-assessment
C Hypernatraemic dehydration and compensated metabolic acidosis
D Acute renal failureE Renal tubular acidosis
2 What is the likely diagnosis Choose ONE answer ONLY from the followingA Hirschsprung disease ndash long segmentB Cystic fibrosis with meconium ileusC Microvillus inclusion diseaseD Cowrsquos milk protein intoleranceE Lactose intolerance
3 What is the investigation of choice Choose ONE answer ONLY from the followingA Rectal biopsy with staining for acetylcholine receptorsB Immunoreactive trypsinC Gastrointestinal endoscopy and biopsyD Stool microscopy and cultureE Stool reducing substances
Case 2A 4-year-old boy presents with a 3 d history of jaundice and a florid rash He has had orange urine and there is no change in his stool colour His family originate from Kosovo and have lived in the UK for the last 8 years He has never left the UK There is no history of blood transfusion or sex-ual abuse The grandmother was recently diagnosed with hepatitis B
On examination he is well apyrexial and mildly jaundiced with cervical and axillary lymphadenopathy He has an exten-sive papular rash over the face extremities and trunk (Figure 2) There is 3 cm hepatomegaly with no splenomegaly or ascites Examination is otherwise normal
Figure 1 abdominal X-ray of baby
Paediatrics and child health 184 202 copy 2008 elsevier ltd all rights reserved
self-assessment
Initial investigations are as follows
haemoglobin 110 gdl (113ndash135)
White blood cell count 108 times 109litre (50ndash150)
Platelet count 278 times 109litre (150ndash400)
inr 10 (08ndash12)
aPt ratio 10 (08ndash13)
sodium 140 mmollitre (135ndash145)
Potassium 42 mmollitre (35ndash50)
Urea 56 mmollitre (25ndash75)
creatinine 65 μmollitre (45ndash120)
total bilirubin 66 μmollitre (0ndash15)
conjugated bilirubin 23 μmollitre (0ndash10)
alanine aminotransferase (alt) 2033 iUlitre (0ndash35)
alkaline phosphatase 987 iUlitre (71ndash234)
Gamma-glutamyl transferase (GGt) 870 iUlitre (0ndash51)
1 What is the name of this rash Choose ONE answer ONLY from the followingA Erythema multiformeB Erythema migransC GianottiminusCrosti syndromeD EczemaE Dermatitis herpetiformis
2 What is the most likely diagnosis Choose ONE Answer ONLY from the followingA Autoimmune hepatitisB Hepatitis BC Hepatitis DD Wilson diseaseE Alpha-1 antitrypsin deficiency
3 What is the best means of management Choose ONE answer ONLY from the followingA Isolation until the jaundice disappearsB ImmunosuppressionC Copper chelating agents and genetic counsellingD Patient and family education with consideration of
antiviral agentsE Liver transplantation
Case 3A 10-month-old boy presents with 3 weeks of vomiting and constipation ndash he is passing hard stools every 2ndash3 days He has fallen from the 9th to below the 04th centile in the last 6 weeks He passed meconium within the first 24 h of life On examina-tion he looks pale and there are some dysmorphic features ndash a short nose long philtrum and wide mouth He has normal heart sounds with a grade 3 ejection systolic murmur loudest at the upper right sternal edge Examination is otherwise normal
Initial investigations are as follows
haemoglobin 91 gdl (113ndash141)
total white blood cell count 124 times 109litre (60ndash170)
Platelet count 407 times 109litre (150ndash400)
sodium 144 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 78 mmollitre (25ndash75)
creatinine 78 μmollitre (45ndash120)
albumin 52 glitre (35ndash50)
corrected calcium 384 mmollitre (238ndash263)
Phosphate 167 mmollitre (099ndash157)
1 What is the most likely diagnosis Choose ONE answer ONLY from the followingA HyperparathyroidismB Acute leukaemiaC Williams syndromeD Hypervitaminosis DE Familial hypocalciuric hypercalcaemia
2 Which investigation would be most useful in establishing the diagnosis Choose ONE answer ONLY from the followingA Intact parathyroid hormone assayB Blood filmC Fluorescent in-situ hybridization for 7q1123 deletionD 25-hydroxyvitamin D assayE Urine calciumcreatinine ratio
3 Which of the following treatments would not be suitable for this patient Choose ONE answer ONLY from the followingA Low calcium dietB Normal saline infusionC FurosemideD CorticosteroidsE Bisphosphonates
Case 4A 10-week-old girl presents with a 2-day history of poor feed-ing Her mother has been concerned about weakness since birth She only has a flicker of movement in the arms none in the legs and has a weak cry She has been passing urine and opening her bowels normally She was born at full term by normal delivery and did not require any resuscitation at birth Normal fetal movements were felt antenatally and there was no polyhydramnios She is the first child of non- consanguineous parents and there is no significant family his-tory On examination she is alert and fixing and following appropriately She has a weak cry and a weak suck There is reduced central and peripheral tone with marked head lag
Figure 2 rash found on examination
Paediatrics and child health 184 203 copy 2008 elsevier ltd all rights reserved
self-assessment
Muscle power is grade 3 out of 5 in the arms and legs There is no muscle or tongue fasciculation and she has absent reflexes throughout The remainder of the examination is normal
Electromyogram shows irregular polyphasic motor unit potentials with marked instability consistent with a dener-vating and re-innervating process (Figure 3)
1 Which of the following additional investigations may be helpful Choose ONE answer ONLY from the followingA Nerve conduction studiesB Creatine kinase assayC Muscle biopsyD SMN1 gene analysisE All of the above
2 What is the most likely cause of this childrsquos symptoms Choose ONE answer ONLY from the followingA Congenital myotonic dystrophyB Duchenne muscular dystrophyC PraderminusWilli syndromeD Spinal muscular atrophyE Mitochondrial myopathy
3 What is the mode of inheritance of this disease Choose ONE answer ONLY from the followingA X-linked recessiveB Autosomal recessiveC Autosomal dominantD MitochondrialE Sporadic
Case 5A 13-year-old girl presents with a 3-week history of fever up to 40degC night sweats and headache She has a reduced appetite with some weight loss She has no other specific symptoms She was on holiday in China 7 months ago On examination she looks well and has a temperature of 387degC There is no lymphadenopathy and no rashes Examination is entirely normal
Results of investigations are as follows
haemoglobin 126 gdl (120ndash160)
total white blood cell count 132 times 109litre (43ndash108)
neutrophil count 115 times 109litre (25ndash75)
Platelet count 244 times 109litre (150ndash400)
Blood film neutrophilia with left shift
erythrocyte sedimentation rate 63 mmh (1ndash20)
c-reactive protein 219 mglitre (0ndash5)
Blood culture Streptococcus intermedius
from anaerobic bottle only
csf culture negative
Magnetic resonance imaging (MRI) of the brain shows acute frontal sinusitis with a large intracranial frontal extra-dural empyema (Figure 4)
1 Which of the following would be appropriate management Choose ONE answer ONLY from the followingA A 12-week course of intravenous antibioticsB Drainage of the frontal sinus followed by 2 weeks of
intravenous antibioticsC Drainage of the empyema followed by 2 weeks of
intravenous antibioticsD Drainage of the empyema and the frontal sinus
followed by 2 weeks of oral antibiotics
1151
1152
1153
1154
1155
1156
1157
1158
1159
1200
50ms 1mV
Figure 3 electromyogram recording from the patient Figure 4 Parasagittal section from mri scan of patient
Paediatrics and child health 184 204 copy 2008 elsevier ltd all rights reserved
self-assessment
E Drainage of the empyema and the frontal sinus followed by 8 weeks of intravenous antibiotics
2 Streptococcus intermedius is a potential pathogen in which of the following infections Choose ONE answer ONLY from the followingA Liver abscessB Urinary tract infectionC MeningitisD Thoracic empyemaE Pneumonia
3 Which of the following statements regarding lsquopyrexia of unknown originrsquo in children is false Choose ONE answer ONLY from the followingA Malignancy is the underlying pathology in 5ndash15 of
casesB An aetiology will be found in over 90 of casesC The most common cause is infectionD A rheumatological cause is found in 10ndash20 of casesE Familial Mediterranean fever can occur in children of
non-Mediterranean ethnicity
Answers
Case 11 AThe anion gap is a useful tool to differentiate the causes of a metabolic acidosis It is calculated by the equation
Anion gap = [Na K ] [Cl HCO ]3+ + minus minus+ minus +
It represents the effect of unmeasured anions on the plasma pH and is normally 10ndash18 mmollitre
2 CMicrovillus inclusion disease is a severe autosomal recessive enteropathy that is typically apparent within hours or days after birth It is the second most common cause of protracted diarrhoea in the newborn after infectious causes It is characterized by severe yellow watery diarrhoea and malabsorption due to hypoplasia andor atrophy of the villi of the small intestine secondary to an inherited defect in the brush border membrane This results in severe dehydration malnutrition and metabolic acidosis due to bicarbonate loss from the gut
3 CDiagnosis of microvillus inclusion disease is made on small bowel biopsy Electron microscopy findings are of intracellular brush border inclusions and densely packed apical cytoplasmic vesicular bodies indicating microvillous atrophy There is no cure Treatment is supportive with total parenteral nutrition and consideration of small bowel transplantation
Further reAding
Goulet O ruemmele f causes and management of intestinal failure
in children Gastroenterology 2006 130(suppl 1) s16ndash28
rhoads Jm Vogler rc lacey sr et al microvillus inclusion disease
In vitro jejunal electrolyte transport Gastroenterology 1991
100 811ndash817
Case 21 CGianottindashCrosti syndrome is a distinct self-limiting rash commonly associated with viral infections in children between 2 and 6 years of age It presents as multiple pink to redminusbrown papules or papulovesicles which may be pruritic and can become confluent Gianotti and Crosti initially described the exanthema as associated with hepatitis B virus and they termed it papular acrodermatitis of childhood It can occur in several viral diseases eg hepatitis A B and C coxsackie viruses and cytomegalovirus
2 BHepatitis is a syndrome characterized by inflammation or injury of liver cells which may develop into cell necrosis and subsequently fibrosis andor cirrhosis Biochemically there are raised liver enzymes The degree of transaminase elevation does not correlate with the severity of the disease process Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of viral hepatitis
3 DHepatitis B infection is transmitted via blood sexually or vertically Infection may be acute or chronic Diagnostic markers are the presence of surface antigen (HBsAg) and HBV DNA The presence of e antigen (HBeAg) indicates high infectivity Infected newborns have a 95 risk of becoming carriers this risk decreases with infection acquired later in childhood Approximately 15ndash25 of HBV carriers will die from cirrhosis or hepatocellular carcinoma Extrahepatic findings are more common in older children and include membranous glomerulonephritis and GianottiminusCrosti syndrome Fulminant hepatic failure occurs in severe cases resulting in persistent jaundice encephalopathy and coagulopathy Management includes counselling family members monitoring for ongoing liver disease and consideration of antiviral therapy
Further reAding
Brandt O abeck d Gianotti r Burgdorf W Gianotti crosti
syndrome J Am Acad Dermatol 2006 54 136ndash145
slowik mK Jhaveri r hepatitis B and c viruses in infants and
young children Semin Pediatr Infect Dis 2005 16 296ndash305
Case 31 CHypercalcaemia is uncommon in infancy The most common symptoms in this age group are irritability vomiting and constipation It may be a manifestation of Williams syndrome vitamin D or calcium excess as well as disorders associated with reduced bone formation such as hypophosphatasia or increased bone resorption such as malignancy Occasionally
Paediatrics and child health 184 205 copy 2008 elsevier ltd all rights reserved
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-
SympoSium neonatology
isotonic crystalloid to be as effective as albumin for the treat-ment of hypotension but none has examined either the relative or actual effectiveness in resuscitation A recent blinded randomized study comparing normal saline albumin or no volume expansion in a normovolaemic asphyxiated neonatal animal model showed that volume expansion was not beneficial and made a number of parameters worse36
NaloxoneNaloxone is not recommended as part of the initial resuscita-tion of newborns with respiratory depression Before it is given supporting ventilation should have restored the heart rate and colour The dose is 100 μgkg intravenously or intramuscularly Tracheal administration cannot be recommended Although administration of naloxone to neonates who have been exposed to maternal opioids during labour is a practice of long-standing it lacks the proper evidence of efficacy
Non-response to resuscitation
There are few more frightening situations professionally than applying the correct interventions in resuscitating or stabilizing a baby and getting no response Each stage must be adequately performed before moving onto the next and this requires regular reassessment When experienced help is needed at a newborn resuscitation it is usually the airway and ventilation that require correction If the heart rate does not increase this usually means that the lungs have not been successfully aerated In some cases however it may mean that the heart cannot respond as the cir-culation is inadequate In this situation the only way to check that the lungs have been successfully aerated is to see the chest move with ventilation or to obtain evidence of ventilation from a detector of exhaled carbon dioxide If you do not see chest movement after another five breaths the most likely cause is an obstructed airway either due to incorrect positioning or because the jaw has not been drawn forwards An oropharyngeal airway can be very helpful at this point especially in the term baby Only very occasionally is the airway blocked by mucus vernix blood or meconium but if the airway is guaranteed and there is no heart rate response or chest movement this should be sought by direct suction of the trachea even in the absence of any meconium staining of liquor Pneumothoraces can occur spontaneously after delivery but are rare at resuscitation carried out with pressure-limited devices Equally rare are diaphragmatic hernias that have not been diagnosed antenatally giving problems at resuscitation
If the chest is moving but the heart rate has not responded to resuscitation consider rare possibilities such as fetal blood loss pneumothorax or heart block (mothers with undiagnosed systemic lupus erythematosis delivered for fetal bradycardia) as possibilities With adequate ventilation there is no evidence of oxygen concentrations less than 100 being responsible for prolonged bradycardia or failure to respond although current practice would support increasing the delivered oxygen concen-tration if resuscitation had been commenced using air
Outcome
The prognosis for the full-term baby subjected to sudden acute asphyxia is usually good provided the episode does not last for
paeDiatRiCS anD CHilD HealtH 184 17
long Most babies resuscitated from primary apnoea have no sequelae secondary to the resuscitation Many babies who start to breathe again regularly within 20 min of the circulation being restored recover completely but it is rare for a baby who is still gasping after 30 min to recover
The prognosis for the preterm baby of less than about 34 weeksrsquo gestation subjected to severe acute anoxia is less predict-able This is because of the risk of secondary intraventricular haemorrhage or periventricular intracerebral haemorrhage andor infarction after even a relatively brief asphyxial episode espe-cially in the period immediately around birth
The effects of chronic hypoxia are also difficult to predict but a reasonably clear idea of the extent of the problem should be obtainable within 36ndash48 h of the original chronic asphyxial insult A mild short-lasting state of hyperexcitability usually car-ries a good prognosis even if there is seizure activity but more severe symptoms can be associated with permanent handicap This is seen especially in infants with encephalopathy requiring ventilation
REFERENCEs
1 Biarent D Bingham R Richmond S et al european Resuscitation
Council guidelines for Resuscitation 2005 Section 6 paediatric life
support Resuscitation 2005 67(suppl 1) S97ndashS133
2 international liaison Committee on Resuscitation part 7 neonatal
resuscitation Resuscitation 2005 67 293ndash303
3 Singh J Santosh S Wyllie J mellon a effects of a course in
neonatal resuscitation - evaluation of an educational intervention
on the standard of neonatal resuscitation Resuscitation 2006 68
385ndash389
4 palme-Kilander C methods of resuscitation in low-apgar-score
newborn infants - a national survey Acta Paediatr 1992 81
739ndash744
5 Kroll l twohey l Daubeney p et al Risk factors at delivery and
the need for skilled resuscitation Eur J Obstet Gynecol Reprod Biol
1994 44 175ndash177
6 Wyllie Jp Resuscitation of the newborn The Foundation Years
2007 3(4) 153ndash157
7 Richmond S ed newborn life Support Resuscitation at Birth
london Resuscitation Council 2006
8 Ceriani Cernadas Jm Carroli g pelligrine l et al the effect of timing
of cord clamping on neonatal venous hematocrit values and clinical
outcome at term a randomized controlled trial Pediatrics 2006
117 e779ndashe786
9 mercer JS Vohr BR mcgrath mm padbury JF Wallach m oh W
Delayed cord clamping in very preterm infants reduces the incidence
of intraventricular hemorrhage and late-onset sepsis a randomized
controlled trial Pediatrics 2006 117 1235ndash1242
10 Dahm lS James lS newborn temperature and calculated heat loss
in the delivery room Pediatrics 1972 49 504ndash513
11 Stephenson J Du J tk o the effect of cooling on blood gas
tensions in newborn infants J Pediatr 1970 76 848ndash852
12 gandy gm adamsons Jr K Cunningham n Silverman Wa James lS
thermal environment and acid-base homeostasis in human infants
during the first few hours of life J Clin Invest 1964 43 751ndash758
13 gluck l Kulovich mV eidelman ai et al Biochemical development
of surface activity in mammalian lung pulmonary lecithin synthesis
0 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
in the human fetus and newborn and etiology of the respiratory
distress syndrome Pediatr Res 1972 6 81ndash99
14 Vohra S Roberts RS Zhang B Janes m Schmidt B Heat loss
prevention (Help) in the delivery room a randomised controlled
trial of polyethylene occlusive skin wrapping in very preterm infants
J Pediatr 2004 145 750ndash753
15 owen CJ Wyllie Jp Determination of heart rate in babies at birth
Resuscitation 2004 60 213ndash217
16 orsquoDonnell Cp Kamlin Co Davis pg Carlin JB morley CJ Clinical
assessment of infant colour at delivery Arch Dis Child Fetal
Neonatal Ed 2007 92 F465ndashF467
17 international liaison Committee on Resuscitation part 13 neonatal
Resuscitation guidelines Circulation 2005 112(suppl 24)
iV188ndashiV195
18 leone ta Rich W Finer nn neonatal intubation Success of
pediatric trainees J Pediatr 2005 146 638ndash641
19 orsquoDonnell Cp Kamlin Co Davis pg morley CJ endotracheal
intubation attempts during neonatal resuscitation success
rates duration and adverse effects Pediatrics 2006 117
e16ndash21
20 Repetto Je Donohue pa-CpK Baker SF Kelly l nogee lm use of
capnography in the delivery room for assessment of endotracheal
tube placement J Perinatol 2001 21 284ndash287
21 gandini D Brimacombe JR neonatal resuscitation with laryngeal
mask airway in normal and low birth weight infants Anesth Analg
1999 89 642ndash643
22 esmail n Saleh m ali a laryngeal mask airway versus endotracheal
intubation for apgar score improvement in neonatal resuscitation
Egypt J Anesthiol 2002 18 115ndash121
23 Wiswell te gannon Cm Jacob J et al Delivery room management
of the apparently vigorous meconium-stained neonate results of
the multicenter international collaborative trial Pediatrics 2000
105 1ndash7
24 Vain ne Szyld eg prudent lm Wisewell te aguilar am Vivas ni
oropharyngeal and nasopharyngeal suctioning of meconium-stained
neonates before delivery of their shoulders multicentre randomised
controlled trial Lancet 2004 364 597ndash602
25 Bjorklund lJ ingimarsson J Curstedt t larsson a Robertson B
Werner o lung recruitment at birth does not improve lung function
in immature lambs receiving surfactant Acta Anaes Scand 2001 45
986ndash993
26 Bjorklund lJ ingimarsson J Curstedt t et al manual ventilation
with a few large breaths at birth compromises the therapeutic effect
of subsequent surfactant replacement in immature lambs Pediatr
Res 1997 42 348ndash355
paeDiatRiCS anD CHilD HealtH 184 17
27 taskar V John J evander e Robertson B Jonson B Surfactant
dysfunction makes lungs vulnerable to repetitive collapse and re-
expansion Am J Respir Crit Care Med 1997 155 313ndash320
28 muscedere Jg mullen JB gan K Slutsky aS tidal ventilation at low
airway pressures can augment lung injury Am J Respir Crit Care Med
1994 149 1327ndash1334
29 nilsson R grossman g Robertson B Bronchiolar epithelial lesions
induced in the premature rabbit neonate by short periods of artificial
ventilation Acta Pathol Microbiol Scand 1980 88 359ndash367
30 probyn me Hooper SB Dargaville pa et al positive end expiratory
pressure during resuscitation of premature lambs rapidly improves
blood gases without adversely affecting arterial pressure Pediatr
Res 2004 56 198ndash204
31 Wood Fe morley CJ Dawson Ja et al improved techniques
reduce face mask leak during simulated neonatal resuscitation
study 2 Arch Dis Child Fetal Neonatal Ed in press doi101136
adc2007117788
32 tan a Schulz a orsquoDonnell CpF Davis pg air versus oxygen for
resuscitation of infants at birth Cochrane Database Syst Rev 2004
(3) CD002273
33 Davis pg tan a orsquoDonnell Cp Schulze a Resuscitation of newborn
infants with 100 oxygen or air a systematic review and meta-
analysis Lancet 2004 364 1329ndash1333
34 Dawes g Fetal and neonatal physiology Chicago year Book
publisher 1968 p 141ndash159
35 Ziino aJa Davies mW Davis pg epinephrine for the resuscitation
of apparently stillborn or extremely bradycardic newborn infants
Cochrane Database Syst Rev 2003 (2) CD003849
36 Wyckoff m garcia D margraf l perlman J laptook a Randomized
trial of volume infusion during resuscitation of asphyxiated neonatal
piglets Pediatr Res 2007 61 415ndash420
Practice points
bull Resuscitation at birth is different from that at all other times
of life
bull a standard approach can be applied to most newborn
resuscitation
bull guidelines are based on a rigorous evaluation of evidence
where possible
bull evidence is sparse but evolving
bull most preterm babies require stabilization rather than
resuscitation
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Acidndashbase physiology and blood gas interpretation in the neonateSusern tan
morag Campbell
Abstractacidndashbase balance describes the complex processes that work to main-
tain a stable extracellular pH for optimal cellular function the process
of balancing the production and neutralization of tissue acid provides a
great challenge for newborn infants who have significantly higher rates
of acid production than adults Factors which help maintain a stable
acidndashbase balance include buffers the respiratory system and renal sys-
tem Both intracellular and extracellular buffers resist changes in pH
the most important extracellular buffer system for maintaining stable
pH is the bicarbonate system in response to acidosis or alkalosis the
respiratory system balances the production of acid with the clearance
of Co2 by altering respiratory rate the kidneys provide a delayed but
sustained response to pH imbalance by excreting either acidic or alkaline
urine in response to systemic acidosis and alkalosis respectively in sick
premature infants these systems have a limited capacity completely to
control pH this review discusses the physiology of the three systems
which control acidndashbase balance patterns of clinical abnormalities in
acidndashbase status and their underlying causes are discussed We present
a systematic approach to blood gas analysis and interpretation in new-
born infants
Keywords acidosis alkalosis bicarbonate bloodndashgas analysis
metabolic pH
Introduction
Blood gas analysis is a routine procedure performed on newborn babies receiving respiratory support in the neonatal intensive care The combination of invasive and non-invasive assessment of ventilation and oxygenation enables clinicians appropriately to modify respiratory care according to each individual babyrsquos rapidly changing clinical status
Understanding the fundamentals of acidndashbase balance helps us to use blood gas analysis not only to assess respiratory sta-tus but also to provide information on metabolic status and the adequacy of tissue perfusion
Susern Tan MBBS MRCP is Clinical Fellow at the Neonatal Intensive Care
Unit 6th Floor North Wing St Thomasrsquo Hospital London SE1 7EH UK
Morag Campbell MBChB MRCP is Consultant Neonatologist at the
Neonatal Intensive Care Unit 6th Floor North Wing St Thomasrsquo
Hospital London SE1 7EH UK
paeDiatRiCS anD CHilD HealtH 184 17
What is understood by acid-base balance
Acidndashbase balance refers to the complex physiological processes used by the body to maintain a stable extracellular pH1 A serum pH within the range of 735ndash745 provides the ideal environment for cellular metabolism Maintaining a stable pH is critical as the metabolic activity of proteins is pH dependent and small changes in hydrogen ion (H+) concentration can potentially alter physio-logical function
Acids are substances that yield free H+ in solution while a base accepts H+ and in solution combines with an acid to neu-tralize it In the normal metabolic state H+ are continuously pro-duced and neutralized to maintain a steady pH balance12 The rate of H+ production is two to three times higher in neonates because of their rapid growth rates and increased acid production from protein turnover and bone mineralization The challenge of maintaining a stable pH through processing and neutralizing H+ is therefore greatest in newborn infants
Using exact values of H+ concentration to assess acidndashbase status is cumbersome and it is more commonly expressed as pH defined by the equation
pH = minuslog H+
Maintaining acidndashbase balance
The balance between production and excretion of acids in the body is controlled by buffer systems which have an immediate effect and by the respiratory and the renal systems
Buffer systemsBuffer solutions resist change in pH when acid or alkali is added due to their capacity to absorb or give up H+ The three main buffer systems in the body are the bicarbonate phosphate and protein systems1ndash3 The protein and phosphate buffer systems are intracellular and act as lsquosinksrsquo for extracellular H+ which are exchanged with intracellular potassium (K+) and sodium ions (Na+) In an acute metabolic acidosis hyperkalaemia may develop due to this H+ exchange4
The bicarbonate buffer system is extracellular and consists of a mixture of carbonic acid (H2CO3) and sodium bicarbon-ate (NaHCO3) This buffer system helps maintain a stable pH by soaking up excess H+ with HCO3
minus which in solution forms carbonic acid (H2CO3) Carbonic acid is a weak acid and readily dissociates to give CO2 which is transported in dissolved form to the lungs for excretion
H+ + HCO3minus harr H2CO3 harr H2O + CO2
The bicarbonate system therefore completes the neutraliza-tion of excess H+ and a stable plasma pH is maintained The relationships between pH HCO3
minus and CO2 in this system are described by the HendersonndashHasselbalch equation15
pH = 61 + log HCO3minus003 times CO2
where 61 is the log of the dissociation coefficient of carbonic acid and 003 the solubility of CO2 in plasma Buffers are most potent when there are equal amounts of H+ and HCO3
minus in solution The
2 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
bicarbonate system is not a potent buffer however as HCO3minus
and CO2 are readily altered by the body this system plays a very powerful role in pH homeostasis15
Respiratory regulationThe respiratory system adapts within minutes to hours as part of the acute response to acidosis This system modifies pH by balancing production of H+ with ventilatory clearance of CO2
H+ directly stimulates chemoreceptors in the respiratory cen-tre of the brainstem producing an increase in respiratory rate26 The response to respiratory acidosis is very rapid as CO2 easily diffuses across the bloodndashbrain barrier however in metabolic acidosis compensation is delayed until plasma bicarbonate fully equilibrates with cerebrospinal fluid (CSF) bicarbonate There is an inverse relationship between alveolar ventilation and partial pressure of dissolved carbon dioxide (PaCO2) a reduction in alveolar ventilation raises PaCO2 and decreases pH Changes in pH therefore affect alveolar ventilation and conversely changes in alveolar ventilation cause significant changes in pH
Renal regulationThe kidneys provide a delayed but sustained response to acidndashbase imbalances by excreting either acidic or alkaline urine In full-term and preterm babies the capacity for acid excretion and bicarbonate reabsorption is reduced as glomerular filtration rates are low and tubular function immature7 Renal function matures with gestation postnatal age and glucocorticoid and thyroid hormones78 Due to their limited capacity to preserve HCO3
minus newborn infants have lower serum bicarbonate levels and are predisposed to acidosis7
Bicarbonate is not effectively reabsorbed due to its size and electrical charge Instead intraluminal HCO3
minus combines with secreted H+ in tubular luminal fluid to produce carbonic acid which dissociates to give H2O and CO2 This CO2 diffuses into tubular cells combines with intracellular H2O and forms carbonic acid which liberates HCO3
minus and H+ HCO3minus is then
recovered to the circulation by exchange for chloride ions (Clminus) through the basal cell membrane247
Renal acid secretion occurs at all sites except the loop of Henle Primary active transport accounts for 5 and secondary for the remaining 95 of total H+ excretion Secondary trans-port involves an exchange between luminal Na+ and intracel-lular H+ Both ions bind to a membrane transport protein The Na+ concentration gradient between the tubular lumen and cells enables Na+ drag into the cell which generates energy to fuel active H+ excretion into the tubular lumen1ndash47
Quantifying acidosis
Standard base excess is a calculated value derived from PaCO2 and pH It is expressed as the mmollitre of base above or below normal buffer bases required to correct the pH to 74 at a PaCO2 of 40 mmHg A negative base excess or base deficit indicates an acidosis while a positive base excess indicates a relative alkalosis15
Anion gap is the measured difference between anions and cations in the blood
Anion gap = (Na+ + k+) minus (HCO3+Clminus)
paeDiatRiCS anD CHilD HealtH 184 17
Calculation of the anion gap enables clinicians better to define the underlying cause of a metabolic acidosis9 The common causes of an increased anion gap acidosis in neonates include lactic acidosis due to tissue hypoperfusion and hypoxia it may also be seen with certain inborn errors of metabolism and in uraemia910 The anion gap can help distinguish between the rela-tively benign non-anion gap hyperchloraemic acidosis seen in premature infants and a pathological lactic acidosis due to poor end-organ perfusion1011
Strong ion theory
Stewart described a complex acidndashbase model which proposed that H+ concentration results from the dissociation of water which is influenced by PaCO2 the strong ion difference and plasma weak acids12
Strong ions are ions that dissociate at normal body pH and include Na+ K+ and Clminus Weak acids in plasma which contrib-ute include albumin inorganic phosphate and plasma proteins their concentrations do not change with pH and are therefore a constant The effect of these factors and other unmeasured tissue ions on acidndashbase status can be quantified by the calculation of the strong ion gap (SIG)112 In the neonatal unit it is perhaps more important that we consider how principles of this model may relate to acidndashbase status rather than fully to quantify the SIG Theoretically low albumin and phosphate levels which fre-quently occur in premature infants by reducing the concentra-tion of weak acids can produce a relative alkalosis while high phosphate levels in renal failure may contribute to acidosis
Tissue oxygenation
Oxygenation is closely linked to acidndashbase status as optimal cel-lular function requires oxygen to fuel aerobic metabolism and produce energy In hypoxic conditions anaerobic metabolism predominates which is energy inefficient and results in a lactic acidosis1011
Tissue oxygen availability is related to regional blood flow haemoglobin level and haemoglobin oxygen affinity Arterial blood gases measure the partial pressure of dissolved oxygen (PaO2) which represents a small component of total oxygen con-tent the majority being transported bound to haemoglobin The relationship between percentage haemoglobin saturation (SaO2) and PaO2 is described by the sigmoidal oxyhaemoglobin disso-ciation curve which enables us to relate the two measures to each other235 The affinity of haemoglobin for oxygen is altered by local tissue factors Increases in temperature H+ PaCO2 and 23-diphosphoglycerate (DPG) levels shift the oxyhaemoglobin dissociation curve to the right reducing affinity for oxygen Decreases in temperature H+ PaCO2 and 23-DPG levels shift the curve to the left increasing oxygen affinity1ndash35 In the body haemoglobin oxygen affinity continuously changes increasing in the lungs to enable efficient oxygen uptake and decreasing at tissue level to provide efficient oxygen delivery to metabolically active tissues
Avoiding both hypoxia and hyperoxia is important in the neo-natal unit as deleterious effects of hypoxia are seen in infants with pulmonary hypertension1314 while hyperoxia is associated with an increased incidence of retinopathy of prematurity1516
3 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Clinical acidndashbase imbalances
Clinical acidndashbase imbalances can be respiratory metabolic or a mixture of both These abnormalities may be corrected by the acidndashbase regulatory mechanisms in the body in an attempt to maintain normal pH (Figure 1)
Respiratory acidosisThis occurs when any disorder leads to decreased alveolar ventilation Common causes of respiratory acidosis are listed in Table 1 Reduced respiratory clearance of CO2 means more dissolved CO2 accumulates in the plasma leading to increased production of carbonic acid and H+ Through chemoreceptor stimulation respiratory acidosis rapidly alters ventilation in an attempt to reduce CO226 Chemoreceptor mediated ventila-tory increases may only partly adjust in premature infants with underlying lung disease In babies with a sustained respiratory acidosis eg in chronic lung disease then metabolic compen-sation occurs through increased renal excretion of H+ and reabsorption of HCO3
minus slowly restoring pH to around 80 of normal47
paeDiatRiCS anD CHilD HealtH 184 17
The management of PaCO2 levels in infants receiving mechan-ical ventilation has important clinical implications Premature babies have impaired cerebral autoregulation17 and adverse neurological sequelae are reported in association with high PaCO2 levels18ndash20 Ventilation strategies which advocate lsquoper-missive hypercarbiarsquo have been developed to minimize airways damage from mechanical ventilation21 Published data suggest pulmonary benefits however the safe level of PaCO2 remains to be defined in premature infants2021
Respiratory alkalosisThis occurs when more CO2 is excreted than is produced by the body Pathological conditions leading to respiratory alkalosis are rare Hyperventilation in the neonatal setting is often iatrogenic or may be due to disorders in brainstem control of breathing including hypoxicndashischaemic encephalopathy or primary central nervous system abnormalities (see Table 1)
If respiratory alkalosis is sustained it may be compensated for by reduced reabsorption of filtered bicarbonate Reported adverse associations of low PaCO2 include periventricular leuco-malacia and intraventricular haemorrhage1922
K+
H+
Overventilation
CO2 + H2O harr H2CO3 harr H+ + HCO3ndash
Bicarbonate Buffer
Intracellular Buffer
uarr H+ excretionuarr HCO3
ndash absorption
uarr buffered H+
(NH4+ H2PO4
ndash)uarr ventilation rate
RespiratoryAcidosis
MetabolicAcidosis
darr CO2and uarr pH
RespiratoryAlkalosis
MetabolicAlkalosis
darr H+ anduarr pH
darr ventilation rate
uarrCO2
and darr pH
darr H+ excretiondarr HCO3
ndash absorption
uarrH+ and
darr pH
Brain
Brain
Intracellular Buffer
H+
K+
Sepsis
HypoxiaRDS
Metabolismand growth
Diuretics
Airwayobstruction
Neuromuscularproblems
IEM
Gastric losses
+ +
ndash -
Renal BufferRespiratory Buffer
Figure 1 mechanisms for regulation of extracellular pH iem inborn errors of metabolism RDS respiratory distress syndrome
4 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Common causes of acidndashbase imbalances
pH PCO2 H2CO3 Base excess Common neonatal causes
Respiratory acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
uarr normal normal bull upper airway obstruction choanal atresia
pierre-Robin sequence
bull lung abnormalities respiratory distress
syndrome transient tachypneoa of
newborn pneumonia meconium aspiration
syndrome pulmonary hypoplasia
congenital pulmonary malformations
bull Central hypoventilation hypoxic-ischaemic
encephalopathy intracranial haemorrhage
bull neuromuscular insufficiency congenital
myopathies congenital neuropathies
bull iatrogenic inadequate ventilatory settings
Compensated lower limit
of normal
uarr uarr gt+3
metabolic acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
normal darr ltminus3 increased anion gap
bull lactic acidosis sepsis hypoperfusion
shock necrotizing enterocolitis
bull inorganic acidosis inborn errors of
metabolism renal failure
normal anion gap
bull increased gastrointestinal H2Co3 losses
ileostomy diarrhoea
bull Renal tubular acidoses
Compensated lower limit
of normal
darr darr ltminus3
Respiratory alkalosis Uncompensated gt 745 darr normal normal bull iatrogenic excessive ventilatory settings
bull Compensatory hyperventilation hypoxic-
ischaemic encephalopathy
Compensated higher limit
of normal
darr darr ltminus3
metabolic alkalosis Uncompensated gt 745 normal uarr gt+3 bull gastric losses vomiting non-replacement
of excessive nasogastric aspirates
bull thiazide and loop diuretics
bull Hypokalaemia
Compensated higher limit
of normal
uarr uarr gt+3
Table 1
Metabolic acidosisThis frequently affects infants in the neonatal unit and has many causes1011 (see Table 1) There may be overproduction of tissue acid impaired acid clearance gastrointestinal loss of bicarbonate or an exogenous increased acid load eg chloride total paren-teral nutrition (TPN) or albumin1ndash323
Calculation of the anion gap to distinguish an increased anion gap acidosis from a non-anion gap acidosis is important both for treatment and prognosis1011 Acidosis stimulates respiratory compensation but this is limited in unstable infants Similarly renal compensation with improved HCO3
minus conservation is con-strained by tubular immaturity Treatment of the acidosis should be directed at the underlying cause eg hypoxia hypotension or excess Clminus rather than by administration of base
Metabolic alkalosisThis is unusual in neonates and is most frequently seen in infants with chronic lung disease or heart failure who are receiving diuretics Diuretics cause alkalosis by increasing renal fluid and Na+ losses An active process to reabsorb Na+ occurs in tubule cells which through enhanced H+ secretion and HCO3
minus reab-sorption produce alkalosis27
paeDiatRiCS anD CHilD HealtH 184 17
Metabolic alkalosis may also occur with excessive loss of gas-tric contents eg protracted vomiting or inadequate replacement of nasogastric aspirates (see Table 1)
Interpreting blood gases
Blood gas measurements can provide important diagnostic and prognostic information and a systematic approach to blood gas analysis is described in Table 2 The clinical management of infants with abnormal gases requires a good understanding of acidndashbase physiology and tissue oxygenation and an apprecia-tion of factors which may affect the reliability of samples
Arterial blood sampling is the gold standard however indwelling arterial catheters and arterial stab samples are usually restricted to infants who are critically ill or those who require sig-nificant ongoing intervention Gases are most frequently measured in capillary or venous samples which correlate well with arterial samples for PaCO2 pH and base excess in babies and children receiving intensive care These correlations however are not valid in infants with peripheral vasoconstriction and hypotension2324
Non-invasive monitoring techniques may enable us to reduce the frequency of blood gas sampling Transcutaneous monitoring
5 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
A systematic approach to blood gas analysis
1 Collect the relevant information
bull type of gas ndash capillary or arterial
bull Current respiratory support ndash document level
bull transcutaneous Co2 and Sao2 levels
bull Clarify no significant clinical events before sampling
2 pH accept a range between 730 and 745 in newborn
babies this is lower than in older children is there an
alkalosis (pH gt 745) or an acidosis (lt 730)
3 Co2 aim for a range between 45 and 65 kpa a paCo2 level
more than 65 kpa suggests inadequate alveolar ventilation
while less than 45 kpa suggests hyperventilation Correlate
values with non-invasive measures
4 o2 Can only be assessed from arterial gases aim for pao2
between 60 and 80 kpa Correlate results with pulse
oximetry levels
5 HCo3 and base excess normal HCo3 level is between 20 and
24 mmollitre and bases excess +3 to minus3
6 anion gap look at the anion gap and lactate to help identify
the cause of an acidosis normal lactate levels should be less
than 2 mmollitre
7 Respiratory or metabolic compensation look at the pH and
assess whether it is appropriate for the Co2 level or is there
evidence of compensation
8 interpret use both the clinical history and blood gas
findings to help you identify the primary problem aim your
management at treating the underlying cause
9 Reassess if clinical management changes have been made
repeat the blood gas after an appropriate time interval to
ensure improvement
Table 2
provides a highly accurate and reliable method for measuring PaCO2 through the skin it can however be technically difficult may cause tissue damage and is of limited reliability when peripheral perfusion is reduced25 Continuous end-tidal CO2 measurements correlate well with arterial CO2 values in patients with normal ventilation and perfusion however in babies with lung disease alveolar collapse small tidal volumes and rapid respiratory rates can make these measurements unreliable26 Despite its limitations transcutaneous monitoring provides the best method for CO2 trend monitoring in the neonatal intensive care unit (NICU)25
Oxygen saturation levels can be continuously measured non-invasively using pulse oximetry While oximetry is easy to perform and accurate on occasion SaO2 levels obtained may be unreliable when tissue perfusion is poor or with movement artefact SaO2 monitoring is highly sensitive at detecting hypoxia but is limited in detecting hyperoxia as at levels more than 90 small changes in SaO2 may result in unacceptably large increases in PaO227 It is therefore essential that SaO2 alarm limits are set for all neonates receiving respiratory support to detect hypoxia and prevent hyperoxia1627
Continuous non-invasive monitoring provides invaluable information when managing complex infants in the NICU but it does not replace the need for regular blood gas analysis
paeDiatRiCS anD CHilD HealtH 184 17
ReFeRenCeS
1 Kellum Ja Determinants of blood pH in health and disease
Crit Care 2000 4 6ndash14
2 Quigley R Baum m neonatal acid base balance and disturbances
Semin Perinatol 2004 28 97ndash102
3 Brouillette Rt Waxman DH evaluation of the newbornrsquos blood gas
status Clin Chem 1997 43 215ndash221
4 Chan JC acid-base disorders and the kidney Adv Pediatr 1983 30
401ndash471
5 Siggaard-andersen o the pH-log pCo2 blood acidndashbase nomogram
revised Scand J Lab Invest 1962 14 598ndash604
6 Saetta m mortola Jp interaction of hypoxic and hypercapnic stimuli
on breathing pattern in the newborn rat J Appl Physiol 1987 62
506ndash512
7 Baum m Quigley R postnatal renal development in Seldin DW
giebisch g eds the kidney physiology and pathophysiology new
york lippincott Williams and Wilkins 2000 p 703ndash726
8 ortiz la Quan a Weinberg a et al effect of prenatal
dexamethasone on rat renal development Kidney Int 2001 59
1663ndash1669
9 gabow pa Kaehny WD Fennessey pV goodman Si gross pa
Schrier RW Diagnostic importance of an increased serum anion gap
N Engl J Med 1980 303 854ndash858
10 lorenz Jm Kleinman li markarian K oliver m Fernandez J Serum
anion gap in the differential diagnosis of metabolic acidosis in
critically ill newborns J Pediatr 1999 135 751ndash755
11 Deshpande Sa platt mp association between blood lactate and
acid-base status and mortality in ventilated babies Arch Dis Child
1997 76 F15ndash20
12 Stewart pa modern quantitative acid-base chemistry Can J Physiol
Pharmacol 1983 61 1444ndash1461
13 Dakshinamurti S pathophysiologic mechanisms of persistent
pulmonary hypertension of the newborn Pediatr Pulmonol 2005
39 492ndash503
14 mourani pm ivy DD gao D abman SH pulmonary vascular
effects of inhaled nitric oxide and oxygen tension in
bronchopulmonary dysplasia Am J Respir Crit Care Med 2004
170 1006ndash1013
15 Deulofeut R Critz a adams-Chapman i Sola a avoiding hyperoxia
in infants le 1250 g is associated with improved short- and long-
term outcomes J Perinatol 2006 26 700ndash705
16 Chow lC Wright KW Sola a Can changes in clinical practice
decrease the incidence of severe retinopathy of prematurity in very
low birth weight infants Pediatrics 2003 111 339ndash345
17 Boylan gB young K panerai RB Rennie Jm evans DH Dynamic
cerebral autoregulation in sick newborn infants Pediatr Res 2000
48 12ndash17
18 Kaiser JR gauss CH pont mm Williams DK Hypercapnia during
the first 3 days of life is associated with severe intraventricular
hemorrhage in very low birth weight infants J Perinatol 2006 26
279ndash285
19 Fabres J Carlo Wa phillips V Howard g ambalavanan n Both
extremes of arterial carbon dioxide pressure and the magnitude of
fluctuations in arterial carbon dioxide pressure are associated with
severe intraventricular hemorrhage in preterm infants Pediatrics
2007 119 299ndash305
20 thome uH Carroll W Wu tJ et al outcome of extremely preterm
infants randomized at birth to different paCo2 targets during the
first seven days of life Biol Neonate 2006 90 218ndash225
6 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
21 Carlo Wa Stark aR Wright ll et al minimal ventilation to prevent
bronchopulmonary dysplasia in extremely-low-birth-weight infants
J Pediatr 2002 141 370ndash374
22 okumura a Hayakawa F Kato t et al Hypocarbia in preterm
infants with periventricular leukomalacia the relation between
hypocarbia and mechanical ventilation Pediatrics 2001 107
469ndash475
23 peters o Ryan S matthew l Cheng K lunn J Randomised
controlled trial of acetate in preterm neonates receiving parenteral
nutrition Arch Dis Child 1997 77 F12ndash15
24 yildizda D yapiciolu H yilmaz Hl Sertdemir y Correlation of
simultaneously obtained capillary venous and arterial blood gases
of patients in a paediatric intensive care unit Arch Dis Child 2004
89 176ndash180
25 aliwalas ll noble l nesbitt K et al agreement of carbon
dioxide levels measured by arterial transcutaneous and end tidal
methods in preterm infants 28 weeks gestation J Perinatol 2005
25 26ndash29
26 Hagerty JJ Kleinman me Zurakowski D et al accuracy of a new
low-flow sidestream capnography technology in newborns a pilot
study J Perinatol 2002 22 219ndash225
paeDiatRiCS anD CHilD HealtH 184 17
27 poets CF Wilken m Seidenberg J Southall Dp von der Hardt H
Reliability of a pulse oximeter in the detection of hyperoxemia
J Pediatr 1993 122 87ndash90
Practice points
bull a stable extracellular pH is important for optimal cellular
functioning
bull abnormalities in acidndashbase balance are regulated by buffer
systems and the respiratory and renal tract
bull maintaining a stable pH is challenging for newborn babies
due to their high rates of acid production and immature
regulatory mechanisms
bull arterial or capillary blood gases provide an effective way to
monitor acidndashbase balance in newborns
bull Blood gases should be analysed in a structured manner
assessing pH and then respiratory and metabolic components
bull the treatment of acidndashbase abnormalities should be directed
at the underlying problem not merely at correcting pH
7 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Recognition and management of neonatal seizuresmalcolm levene
AbstractSeizures are the most common major manifestation of central nervous
system dysfunction in the newborn there are many causes but perina-
tal asphyxia and haemorrhagicinfarction lesions account for about 75
there is now considerable evidence that frequent but short seizures in
the neonate affect subsequent neurodevelopmental outcome Studies
using eeg or modified continuous tracing of eeg activity (aeeg or CFm)
have shown that there is often electroconvulsive dissociation this re-
fers to poor correlation between electrical seizures and clinical seizures
Commonly used anticonvulsants appear to increase electroconvulsive
dissociation effective management of neonatal seizures has proved very
disappointing and less than 50 of seizures are abolished by first-line
anticonvulsant medication (phenobarbitone or phenytoin) Drugs such
as midazolam and lidocaine may further reduce seizures but require
more evaluation the challenge is to assess new and more effective anti-
convulsants which are themselves associated with little neurotoxicity
Keywords antiepileptic drugs eeg neonatal seizures neurodegeneration
Convulsions are the most common major neurological sign seen in newborn infants and their incidence estimated from large population studies is 26 per 1000 live births1 Premature infants are over four times more likely to have convulsions than full-term infants12 Neonatal status epilepticus (continuous seizure activity lasting 30 min or more) diagnosed clinically is rare and accounts for only 5 of infants with seizures1 although this is now recognized more frequently as the result of continuous EEG monitoring3
Neonatal convulsions are described as presenting in a num-ber of different ways and various seizure types can be seen in the same baby over a number of hours The frequencies of the various patterns of seizure activity are given in Table 1 In very premature babies and to a lesser extent in term infants minor movement abnormalities may be difficult to identify as subtle seizures These include lip smacking tongue thrusting mouth-ing pedalling type movements of the lower limbs or swimming movements of the arms Apnoea can be a common manifesta-tion of subtle seizures The signs can be protean and vary from baby to baby or even in the same baby Virtually any stereotypic
Malcolm Levene MD FMedSc FRCPCH FRCH is Professor and Head of
Department of Paediatrics and Child Health at University of Leeds Leeds
and Honorary Neonatologist at Leeds General Infirmary Leeds UK
paeDiatRiCS anD CHilD HealtH 184 178
movement may be a manifestation of a seizure disorder in the newborn
Aetiology
The more carefully the fitting baby is investigated the more likely it is that a cause for the seizures will be found A number of recent papers have described the aetiology of neonatal con-vulsions after extensive investigations14 Tekgul et al4 recently studied a consecutive group of full-term infants with evidence of neonatal convulsions (recognized both clinically and on EEG) and reported their outcome Table 2 summarizes these data as well as risk of moderate or severe disability for each causative factor Perinatal asphyxia is the commonest cause for convul-sions in term infants with haemorrhagic or ischaemic lesions also being common
Overall the prognosis for the group of term babies with con-vulsions was good 72 had a favourable outcome Where asphyxia (hypoxicndashischaemic insult) is the cause of neonatal convulsions the outcome is poor in 50 The prognosis for neonatal convulsions when they were due to arterial or cere-brovenous infarction or intracranial haemorrhage was generally good Individually inborn errors are a very rare cause of neo-natal convulsions but in view of the treatable nature of some of these it is essential that these be considered and investigated appropriately5
Patterns of seizure activity in the newborn
Movement pattern Frequency ()
Clonic 50
tonic 20
Subtle 10ndash35 depending on maturity
myoclonic 5
Table 1
Cause incidence and outcome of neonatal convulsions in term infants14
Aetiological factor Incidence () Poor outcome ()
asphyxia 38ndash40 50
Cerebral arteriovenous
infarction
20 0
intracranial haemorrhage 12ndash20 13
Congenital cerebral anomaly 5ndash10 100
Hypoglycaemiahypocalcaemia 3ndash19
infection 3ndash20
inborn error of metabolism 1
unknown cause 10ndash13 0
Refers to moderate and severe neurodevelopmental abnormalitynumbers too small to make meaningful predictions
Table 2
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Controversies in the clinical management of neonatal seizures
In recent years we have learnt much more about the neurobi-ology of seizures and their effect on the developing brain The neonatal brain is in a neurophysiologically hyperexcitable state compared to the more mature brain and therefore is more prone to seizure activity This is due largely to a relative excess of GABA neuroreceptors GABA receptors are usually inhibitory but in the immature brain they have a paradoxically excitatory effect This changes at about term in primates and with progressive develop-ment they adopt a neuroinhibitory role6
The propensity to seizures in the neonatal brain makes resolv-ing the balance of risks between continuing seizure activity on the one hand against potentially adverse effects of therapy on the other a very important equation Added to this is the problem of accurately diagnosing neonatal seizures and whether commonly used anticonvulsants are successful in controlling them
These conundrums can be posed as a series of challenging questions which are discussed below
Do neonatal convulsions cause brain injuryConvulsions are a sign of neurological compromise and may indi-cate significant underlying structural brain damage or biochemi-cal disturbance which may cause further brain damage in its own right There has been considerable debate about the scale of the disability that convulsions cause the immature brain over and above that due to the underlying cause Most of our knowledge comes from studies in rodents and these have provided some tentative answers to this question
Seizures in the mature brain lead to neuronal necrosis but studies in very young rat pups whose brain development is somewhat similar to full-term infants have shown that a series of five brief seizures on five successive days does not cause struc-tural neuronal damage but does produce morphological changes in hippocampal neurones and worryingly deficits in the rat learning and visual spatial memory function in adolescent and adult life7 A single prolonged neonatal convulsion in similarly immature rats does not produce any functional effects8 Others have shown that following priming of the neonatal rat brain by short seizures as described above a further insult comprising induction of status epilepticus in the same rats at an older age causes neuronal necrosis9 This has been referred to as the lsquotwo hit hypothesisrsquo10
A more specific question is does seizure activity in an already significantly compromised brain cause additional neuropathol-ogy Wirrell et al11 studied a series of immature rat pups with the induction of an hypoxicndashischaemic (asphyxial) insult fol-lowed by either chemically-induced fits or a control sham pro-cedure In the more severely asphyxiated animals the degree of brain damage was increased significantly in those that had the additional burden of induced seizures
In summary these studies show that the immature brain is more resistant to short frequent post-seizure damage than the mature brain but despite resulting in no loss of neuronal numbers the function of the brain is permanently affected in later life In the asphyxiated brain seizures appear to have an additional adverse effect on brain damage Furthermore the immature brain that has been lsquoprimedrsquo by early seizures is more
paeDiatRiCS anD CHilD HealtH 184 179
vulnerable to status epilepticus later in life It would appear from these data that frequent seizures in the human infant should be stopped and this begs the question as to whether currently used anticonvulsants effectively control neonatal seizures
Can we rely on clinical versus EEG diagnosis of neonatal convulsionsTraditionally the diagnosis of neonatal convulsions has been made by observation and description of the frequency of abnor-mal movements EEG has been technically difficult in the hostile electrical activity of a neonatal intensive care environment and considerable expertise is required for analysis of the trace It is usually not practical to undertake traditional EEG recordings at the time the baby shows abnormal movements More recently various technological developments have allowed more direct investigation of neuronal electrical activity by either video-EEG or compressed recording of the amplitude integrated EEG (aEEG or CFM)
Rennie et al3 at Kingrsquos College Hospital London have under-taken extensive evaluation of video-EEG and have found that this technique detects many convulsions not recognized by a single channel aEEG or CFM trace Of 19 infants with evidence of convulsions on EEG only four were recognized on CFM but this may have been due to the observersrsquo lack of experi-ence with this technique In other centres that have developed appropriate expertise aEEG or CFM has proved more sensitive to the detection of seizures Video-EEG studies have also shown that many movements interpreted by experienced clinicians to be seizures are not associated with abnormal cortical activity Conversely many electrical seizures are not associated with abnormal movements This is referred to as electroconvulsive dissociation
In summary clinical observation alone to detect the fitting baby is unreliable in that it may either over-detect seizure activ-ity which is not present on EEG or under-detect clinical seizures in infants with EEG-proven convulsions The decision as to which babies to treat with antiepileptic drugs therefore becomes somewhat arbitrary
Do anticonvulsants stop neonatal seizuresAlthough neonatal seizures are common there are few random-ized controlled trials assessing the benefits of antiepileptic drugs (AEDs) in the treatment of this condition Phenobarbitone is the most widely used first-line AED and in an Australasian study 95 of neonatologists and paediatric neurologists used this drug as first-line management12 The most commonly used loading dosage is 20 mgkg but regimens of up to 40 mgkg have been recommended (Table 3)13 Four trials have evaluated the effect of phenobarbitone in abolishing neonatal seizures Two of these studies used EEG to monitor response to the drug1415 and one compared phenobarbitone with phenytoin15 In the latter study seizures were completely controlled in only 43 of babies and in the group where phenytoin was the first drug used com-plete seizure control was achieved in 45 This study switched babies from their first AED to the other if complete control was not obtained on EEG monitoring after exposure to first-line therapy In babies who had been given phenobarbitone as first-line therapy seizure control was only achieved in 57 after phenytoin was added In those given phenytoin first complete
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Dosage regimens for first- second- and third-line anticonvulsants in the neonatal period
Loading dose Second loading dose if first
unsuccessfulMaintenance dose
phenobarbitone 20 mgkg by slow iv injection 10 mgkg iv 25ndash5 mgkg od
phenytoin 20 mgkg iv over 20 min not recommended
midazolam 150ndash200 μgkg iv infusion 1 μgkgmin iv infusion increasing to 5 μgkgmin
until favourable response
lidocaine 2 mgkg iv over 10 min 6 mgkgh for 6 h iv then 4 mgkgh for 12 h then
2 mgkgh for 12 h
lorazepam 005ndash01 mgkg by slow iv injection
Diazepam 03ndash04 mgkg iv over 3ndash5 min
lidocaine should not be used if the infant has previously been treated with phenytoin
Table 3
seizure control was achieved with the adding of phenobarbitone in 62
Boylan et al14 assessed the efficacy of phenobarbitone (20ndash40 mgkg iv over 20 min) in 14 babies monitored by video-EEG in only four was there complete abolition of seizures and in the other 10 electroconvulsive seizure activity increased whereas clinical evidence of seizures reduced This has been termed elec-troclinical dissociation and anticonvulsant drug use in the new-born appears to increase this feature They also showed that the babies least likely to respond to the first-line AED are those with the most abnormal background EEG
Two studies have evaluated the use of phenobarbitone in babies who had sustained significant asphyxial insult at birth Hall et al13 compared high-dose phenobarbitone (mean 39 mgkg) versus standard dose (27 mgkg) and reported fewer convul-sions and a significant reduction of severe disability or death in the high dose group (RR 030 CI 010ndash093) A recent study from India16 of babies with hypoxicndashischaemic encephalopathy ran-domized 25 babies to phenobarbitone (20 mgkg loading dose) and compared them with 20 control babies Only 2 of 25 (4) in the phenobarbitone group developed convulsions compared with 8 of 20 (40) in the control group (p = 001) Because of the specific enrolment criteria (asphyxial insult) neither of these studies is strictly comparable to the studies by Painter et al15 and Boylan et al14 whose intention was to assess the efficacy of first-line anticonvulsant therapy on convulsions of any cause diagnosed either clinically or by EEG
Other anticonvulsants used as second- and third-line drugs have been subject to few studies in the newborn Midazolam is administered as a bolus followed by continuous infusion A recent study17 has shown that in 10 of 13 neonates given intravenous midazolam for status epilepticus control of electri-cal seizures was achieved within the first hour of treatment having been previously shown to be refractory to phenobarbi-tone treatment Some of these babies required a second bolus infusion of midazolam to obtain control of all electrographic seizures
In some parts of Europe lidocaine is used as a third-line anti-convulsant Malingre et al18 evaluated 20 infants refractory to
paeDiatRiCS anD CHilD HealtH 184 180
both phenobarbitone and midazolam and who were then given lidocaine by continuous infusion Lidocaine was effective in abolishing electroconvulsive seizures diagnosed by aEEG in 76 of the treatment courses studied No babies developed cardiac arrhythmias a previously reported complication of lidocaine in older patients As a result of pharmacokinetic studies the dosage regimen has been modified (see Table 3)
In summary phenobarbitone is effective in seizure control in less than 50 of babies and even when combined with phe-nytoin the efficacy of these drugs together remains poor More worrying is the observation that phenobarbitone tends to reduce clinically evident seizures thereby giving the clinician a false sense of security whilst having little or no effect on the num-bers of electroconvulsive disorders This has been summarized appropriately as lsquoafter all these years we still love what doesnrsquot workrsquo19 Both midazolam and lidocaine infusions appear to be effective in abolishing severe seizures in some infants resistant to phenobarbitone Lidocaine should not be given to babies previ-ously exposed to phenytoin for fear of a synergistic adverse effect on cardiac rhythm
Do antiepileptic drugs cause brain damageA riskndashbenefit analysis is needed to evaluate the efficacy of anticonvulsants in stopping neonatal seizures which is poor with standard anticonvulsants as discussed above against the risk of administering the anticonvulsant drugs themselves Phenobarbitone has been reported to have adverse effects on the developing brain including inhibition of brain growth20 neuronal toxicity21 and adverse behavioural and cognitive effects into adult life when administered to young animals22 Phenytoin shows unpredictable plasma levels and potential cardiotoxicity
Recent studies have shown an effect of AED exposure on the developing brain by causing neurodegeneration23 Phenytoin administration to immature rat pups at doses which produce serum levels similar to those achieved in human neonates was associated with widespread neuronal death as a result of apop-tosis (programmed cell death) Phenobarbitone had a similar effect when a dosage regimen similar to 40 mgkg was used and
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
this effect was maximal in the more immature brain Diazepam and clonazepam also resulted in a similar effect Midazolam and lidocaine were not tested in this study The combination of phenobarbitone or phenytoin with diazepam had a particularly profound effect on neurodegeneration
In summary recent data suggest that the commonly used AEDs for neonatal convulsions may in themselves cause neuro-degeneration due to apoptosis with lasting effects on develop-ment Many babies with neonatal convulsions are treated with at least two AEDs and this may produce more severe adverse effects than the seizures themselves
Practical management of neonatal seizures
Assimilation of these data and formulation of a rational policy is difficult when faced with a fitting neonate on an intensive care unit and pressure on the medical staff to lsquodo somethingrsquo but it is important to accept that sometimes doing nothing is preferable to using potentially dangerous drugs in a situation which does not warrant such intervention Many babies who have normal interseizure neurological clinical findings and whose seizures are relatively brief and infrequent probably do not need anticon-vulsant medication A normal or near-normal background EEG trace should reassure the clinician that anticonvulsants can be withheld
Some causes of neonatal convulsions are treatable such as meningitis hypoglycaemia hypocalcaemia and inborn errors of metabolism and each baby should be rapidly and carefully investigated for cause of the convulsions
In some babies clinical assessment of seizures is difficult ie when the baby is very sick small or paralyzed Sometimes it may be difficult to assess the significance of certain movement pat-terns Under these circumstances an EEG may prove to be very helpful In many units EEG is not available out of hours and a simple aEEG or CFM is strongly advised Modern instruments are very simple to apply and prolonged or frequent seizures should be identified with only moderate training The printout can be faxed to a more senior doctor if there is doubt as to what is shown on the trace
The balance of knowledge now is that frequent seizures cause additional damage to the developing brain and that treatment to abolish the seizures is warranted Unfortunately there is little evidence that the majority of seizures can be effectively termi-nated by current standard therapy Furthermore it appears that the more abnormal the background EEG the more difficult it is to control the seizures Nevertheless a written protocol for the management of neonatal convulsions is required on each unit Phenobarbitone and phenytoin remain the mainstay of treat-ment although their effectiveness is disappointing There is little to suggest that midazolam is more effective than lidocaine as third-line therapy but lidocaine is precluded if phenytoin has been previously used
In view of the anxiety as to the neurodegenerative effects on the immature brain of most anticonvulsants used in the neonatal period (particularly when multiple drugs are used) it is prefer-able to use only one drug to maximum dosage before introduc-ing a second In addition the duration of anticonvulsants should be minimized and the drugs stopped at the earliest opportu-nity It is my practice to stop anticonvulsants prior to discharge
paeDiatRiCS anD CHilD HealtH 184 18
from hospital if the baby is neurologically normal on clinical examination
REFEREnCES
1 Ronen gm penney S andrews W the epidemiology of clinical
neonatal seizures in newfoundland a population-based study
J Pediatr 1999 134 71ndash75
2 lanska mJ lanska DJ Baumann RJ et al a population-based study
of neonatal seizures in Fayette County Kentucky Neurology 1995
45 724ndash732
3 Rennie Jm Chorley g Boylan gB et al non-expert use of the
cerebral function monitor for neonatal seizure detection Arch Dis
Child Fetal Neonatal Ed 2004 89 F37ndashF40
4 tekgul H gauvreau K Soul J et al the current etoliologic profile
and neurodevelopmental outcome of seizures in term newborn
infants Pediatrics 2006 117 1270ndash1280
5 Surtees R Wolf n treatable neonatal epilepsy Arch Dis Child 2007
92 659ndash661
6 Ben-ari y Holmes gl effects of seizures on developmental
processes in the immature brain Lancet Neurol 2006 5 1055ndash
1063
7 Holmes gl gairsa Jl Chevassus-au-louis n et al Consequences of
neonatal seizures in the rat morphological and behavioral effects
Ann Neurol 1998 44 845ndash857
8 Stafstrom Ce Chronopoulos a thurber S et al age-dependent
cognitive and behavioural deficits following kainic-acid inducing
seizures Epilepsia 1993 34 420ndash432
9 Schmid R tandon p Stafstrom Ce et al effects of neonatal seizures
on subsequent seizure-induced brain injury Neurology 1999 53
1754ndash1761
10 Hoffmann aF Zhao Q Holmes gl Cognitive impairment following
status epilepticus and recurrent seizures during early development
support for the ldquotwo-hit hypothesisrdquo Epilepsy Behav 2004 5
873ndash877
11 Wirrell eC armstrong ea osman lD et al prolonged seizures
exacerbate perinatal hypoxic-ischemic brain damage Pediatr Res
2001 50 445ndash454
12 Carmo KB Barr p Drug treatment of neonatal seizures by
neonatologists and paediatric neurologists J Paediatr Child Health
2005 41 313ndash316
13 Hall Rt Hall FK Daily DK High-dose phenobarbital therapy in term
newborn infants with severe perinatal asphyxia a randomized
prospective study with three-year follow-up J Pediatr 1998 132
345ndash348
14 Boylan gB Rennie Jm pressler Rm et al phenobarbitone neonatal
seizures and video-eeg Arch Dis Child Fetal Neonatal Ed 2002 86
F165ndash170
15 painter mJ Scher mS Stein aD et al phenobarbital compared with
phenytoin for the treatment of neonatal seizures N Engl J Med
1999 341 485ndash489
16 Singh D Kumar p narang a a randomized controlled trial of
phenobarbital in neonates with hypoxic ischemic encephalopathy
J Matern Fetal Neonatal Med 2005 18 391ndash395
17 Castro Conde JR Borges H Domenech martinez e et al midazolam
in neonatal seizures with no response to phenobarbital Neurology
2005 64 876ndash879
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
18 malingre mm Van Rooij lgm Rademaker Cma et al Development
of an optimal lidocaine infusion strategy for neonatal seizures Eur
J Pediatr 2006 165 598ndash604
19 Sankar R painter mJ neonatal seizures after all these years we still
love what doesnrsquot work Neurology 2005 64 776ndash777
20 Diaz J Schain J Bailey Bg phenobarbital-induced brain growth
retardation in artificially reared rat pups Biol Neonate 1977 32 77ndash82
21 mattson RH phenobarbital toxicity in levy RH Dreifuss Fe
mattson RH et al eds antiepipeptic Drugs 3rd edn new york
Raven 1985 p 341ndash355
22 mikati ma Holmes gl Chronopoulos a et al phenobarbital
modifies seizure-related brain injury in the developing brain Ann
Neurol 1994 36 425ndash453
23 Bittigau p Sifringer m genz K et al antiepileptic drugs and
apoptotic neurodegeneration in the developing brain Proc Natl
Acad Sci U S A 2002 99 15089ndash15094
paeDiatRiCS anD CHilD HealtH 184 182
Practice points
bull the clinician needs to be aware that almost any repetitive
stereotype movement pattern can be a manifestation of
neonatal seizures
bull eeg is important in defining neonatal seizures
bull Frequent short-lived seizures have been shown to cause long-
term neurodevelopmental problems
bull Conventional anticonvulsant medication is ineffective in
abolishing neonatal seizures in greater than 50 of cases
bull there is evidence that exposure of the neonatal brain to
multiple anticonvulsants causes neuronal death
bull Future research is needed to evaluate more effective
anticonvulsants for treating this condition
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
Emotional support for families of sick neonatesMarina nicolaou
cristine Glazebrook
AbstractParents of sick neonates experience high levels of stress anxiety and
depression Most interventions with families of sick infants have focused
on fostering the motherndashinfant relationship through the provision of
information about infant developmental needs or through increased
motherndashinfant contact Many of these studies have reported improved
maternal well-being though there are some concerns about the scope
and practicality of large-scale interventions The few studies to have
prioritized emotional support for parents of sick neonates have pro-
duced encouraging results even interventions requiring relatively few re-
sources such as telephone support parent-to-parent support and group
support have been associated with reduced psychological morbidity for
parents The needs of parents can change throughout their infantrsquos hos-
pitalization and not all want or benefit from the provision of additional
support Thus neonatal intensive care units should aim to provide a
varied flexible and sustainable programme of support options Further
research should focus on the needs of fathers
Keywords mental health neonatal intensive care parents
The admission of an infant to neonatal care is acknowledged to be a source of considerable distress for families This review aims to explore evidence for the psychological impact on families of having an infant in neonatal intensive care and to identify evi-dence for the effectiveness of interventions to promote parental well-being It will conclude with recommendations for strategies to support parents of vulnerable infants and suggestions for fur-ther research
Psychological impact of neonatal care for parents
The majority of research examining the effect on parents of having a sick neonate has focused on families of premature or low birthweight infants Such research has found that parents with a sick neonate exhibit high levels of stress compared to normative samples and to parents of healthy full-term infants1 Singer et al2 examined the stress experienced by mothers of high-risk very low birthweight (VLBW) low-risk VLBW and term
Marina Nicolaou MPhil is a Teaching Assistant at the School of
Community Health Sciences University of Nottingham Nottingham UK
Cristine Glazebrook PhD is a Professor of Health Psychology at the School
of Community Health Sciences University of Nottingham Nottingham UK
PaeDiaTrics anD cHilD HealTH 184 196
infants Several self-report measures were used including the Brief Symptom Inventory the Parenting Stress Index (PSI) the Impact on Family Scale and the Family Inventory of Life Events and Changes (FILE) Mothers of VLBW infants had more psycho-logical distress at 1 month compared to mothers of term infants Mothers of high-risk VLBW infants also reported high psycho-logical distress at 2 years and high levels of parenting stress at 3 years Mothers have also been found to have higher stress levels compared to fathers Shaw et al3 examined the prevalence of acute stress disorder (ASD) in 40 parents whose infants were in the neonatal intensive care unit (NICU) Nearly half of the moth-ers (44) met the criteria for ASD although none of the fathers did Furthermore the severity of the symptoms (measured by the number of concurrent symptoms) was greater for the moth-ers than for the fathers3 The reasons behind this difference have been widely speculated with some believing that it is due to the mothersrsquo greater psychological involvement with the infant as evidenced by their general greater vulnerability to postpartum psychological disorder It could also reflect gender differences in coping style
Having an infant who requires intensive medical care repre-sents a significant emotional burden for families Not only is there extreme anxiety surrounding the infantrsquos health and distress for the childrsquos suffering there is also the unfamiliar and intimidating environment of the NICU to adjust to Hopper in her review of the literature identified sources of stress for parents of sick neo-nates as falling into three areas4 Situational factors included the severity of the infantrsquos illness and how parents adapted to the life crisis of having a sick infant Personal factors involved parental emotions about their roles and the instrumental and informa-tional support which were available to them The third area was classified as environmental sources of stress and included the environment of the NICU and the relationship between parents and members of staff This relationship has been examined by several studies in the nursing literature nurses are seen as ide-ally placed to provide the necessary support and information to parents with sick neonates However whilst some studies have shown that supportive and helpful hospital staff can have a posi-tive effect on parents other studies have highlighted the prob-lems and difficulties which can manifest It has been shown that parents and nurses often have very different ideas about issues eg the necessary skills and competencies needed in an NICU or the characteristics that make a lsquogood motherrsquo
Research has shown that there may be a relationship between high levels of parental stress and an increased likelihood of depression5 Postpartum depression is a psychiatric illness which appears in 10ndash15 of postpartum women Its reported preva-lence rates however have ranged from less than 10 up to 306 depending on the instruments used the population exam-ined and the timing of the research Several factors have been found to be associated with postpartum depression including poor social support and infant-related stressors6 Evidence indi-cates that postnatal depression may be underreported and this is of concern since the mental and psychological health of the mother can affect her relationship with her infant and thus the infantrsquos cognitive and emotional development5 Depressed moth-ers appear to look touch and talk to their infants less frequently and also appear to show fewer positive and more negative faces7 The vocalizations of mothers suffering with depression have also
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
been found to be less effective at promoting cognitive growth and learning in infants8
If researchers are interested in finding ways of providing sup-port for families of sick neonates then they must listen to what such families perceive their needs to be in order to avoid increas-ing anxiety and distress Furthermore the provision of appropri-ate support be it emotional informational or social will enhance parental coping abilities increase self-esteem and reduce anxiety It should be noted though that the research conducted around these issues has often taken lsquosupport needsrsquo as being synony-mous with lsquoinformation needsrsquo Such studies have examined the type the amount and quality of information that parents receive and perceive themselves as needing but have not explored in equal depth the perceived emotional support needs of families who have a sick infant In addition the needs of parents may change throughout their infantrsquos illness Ward examined the per-ceived needs of 52 parents of infants in an NICU9 Parents rated the needs of their hospitalized infant as most important along with the need to be reassured Interestingly they ranked their support needs as least important This research was conducted during the first week of the infantsrsquo hospitalization however which would explain the preoccupation of the parents with the infantrsquos health These results demonstrate that if researchers want to find ways of providing emotional support to parents of sick neonates they must be prepared not only to listen to parents but also to be flexible enough to satisfy the parentsrsquo changing needs and expectations
Interventions aimed at supporting parents
Most interventions that been evaluated in controlled studies have focused on supporting the motherndashinfant relationship and provid-ing information on infant development Many of these interven-tions have included the aim of improving the parental emotional state and thus psychological outcomes such as stress or anxi-ety have been assessed However few studies appear to include fathers This means that strategies implemented to provide emo-tional support to families of sick neonates are often derived from interventions tailored for mothers even though fathers may have different emotional needs
A wide range of interventions with mothers and infants has been evaluated in the NICU Increasing motherndashinfant contact through kangaroo care has been found to reduce maternal anxiety1011 and educational programmes delivered to fami-lies in the NICU have also been associated with reduced emo-tional difficulties in parents12ndash14 Kaaresen and colleagues implemented an intervention which consisted of eight sessions before discharge and four home visits all by trained nurses The sample included 71 premature infants in the intervention group 69 premature infants in the control group and 74 infants in the full-term control group The randomized controlled trial found that the intervention reduced parenting stress in both mothers and fathers of premature infants compared to controls to a level equivalent to parents in the term control group13 At 6 months corrected age mothers of preterm infants who had not received the intervention had total PSI scores which were 17 points higher than the mothers of infants born at term (an effect size of 057) A similar study evaluated the efficacy of an educationalndashbehavioural programmendashCreating Opportunities for
PaeDiaTrics anD cHilD HealTH 184 19
Parent Empowerment (COPE) ndash through a randomized controlled trial with 260 families of premature infants14 COPE was a four-phase educationalndashbehavioural programme which began as early as 2ndash4 d after mothers had given birth and continued until 1 week after discharge from the NICU The programme consisted of audiotaped and written infant behaviour information along with photographs which focused on common behaviours and characteristics of premature infants It also included various par-ent activities in the form of a four-phase workbook which aimed to assist mothers in the implementation of the experimental infor-mation COPE was found significantly to reduce maternal stress in the NICU as well as maternal anxiety and depressive symptoms after hospitalization In contrast a cluster randomized trial of a parenting intervention delivered to mothers of very premature infants from soon after birth showed no benefits for parenting stress1 The authors hypothesized that the intervention had not been of sufficient intensity particularly in the weeks surrounding discharge Neonatal care presents a significant barrier to parent-ing in the early weeks following a very preterm birth and so inter-ventions which focus on the developmental needs of infants and the parentndashchild relationship should particularly aim to support parents as they take on the parenting role There was also concern that the intervention had failed to reach those most at risk
Since large-scale projects can be costly to implement and may often fail to reach the families in most need it may be wiser to focus on intervention programmes which are more practical and easier to implement within a neonatal care setting Research has shown that even interventions which are based on one-off meet-ings with parents of sick neonates can be effective Jotzo and Poets examined the effect of an intervention programme aimed at reducing the severity of traumatic responses as a result of giv-ing birth prematurely15 Their programme consisted of a one-off intervention meeting along with additional psychological help throughout the hospitalization of the infant The meeting cov-ered a variety of issues including a reconstruction of the events shortly before and after the infantrsquos birth relaxation techniques discussion of coping strategies available resources and social support and support during emotional outbursts The measures used included the Impact of Event Scale (IES) and the Peritrau-matic Dissociative Experience Questionnaire At discharge the mothers who received the intervention were found to have a significantly lower traumatic impact as a result of premature birth Furthermore fewer mothers in the intervention group showed symptoms of clinically significant psychological trauma at discharge compared to mothers in the control group (36 vs 76)15 The lsquoParents Circle Programrsquo is another intervention with a similar structure16 This consisted of a 90 min session for parents with the aim of enhancing the developing relationship between parents and infants and to offer parents support A total of 104 parents (59 mothers and 45 fathers) and 44 members of hospital staff were asked to evaluate the programme and their results were analysed using content analysis Families reported gaining perspective on their situation feeling supported becom-ing aware of cues and optimizing interactions and becoming aware of available resources Parents and staff alike felt that participating in the intervention helped parents overcome the difficulties associated with the early time of their infantrsquos hos-pitalization Additional studies have also found positive results with fairly minimal interventions including discussion groups
7 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
in the NICU music during kangaroo care and pairing mothers of sick neonates with trained mothers who had been through similar experiences
Parent support programmes
Parent support programmes (PSPs) which are based in NICUs can provide parents with the opportunity to talk to parents who have been in similar situations and also to discuss their emo-tions with professionals who can help them cope with their situa-tion111718 The parent-to-parent support programme for mothers of preterm infants evaluated by Preyde and Ardal included edu-cational parental support group meetings and individual par-ent-to-parent support (primarily telephone support)19 Measures used included the Parental Stressor Scale NICU the State and the Trait Anxiety Inventories and the Beck Depression Inven-tory After 4 months of participation mothers in the intervention group reported lower levels of stress state anxiety and depres-sion compared to control group mothers The authors speculated however that the participants who were able to meet face to face with other parents were those who benefited the most Hurst conducted a comprehensive survey of an NICU-based PSP This PSP was provided in a variety of formats including a weekly parent support group hospital visitation and 24-h telephone sup-port20 Of the 477 participants 303 families used the PSP dur-ing a 2-year evaluation period with 78 using only one form of support and 18 using two forms Of a sub-sample of 48 parents asked to complete an evaluation of the PSP 92 stated that they would recommend such a programme to other parents Furthermore the majority of parents felt that it made them feel supported and helped them deal with their emotions20 This is an indication that such programmes can be very successful in sup-porting parents throughout their infantrsquos hospitalization It also shows that it can be beneficial to give parents several options and formats when it comes to such support services It is impor-tant to consider though that both the Hurst and the Preyde and Ardal studies found that some participants did not find the sup-port programmes helpful even reporting that they had caused them increased stress and anxiety Therefore it should not be assumed that support programmes will suit every individual and will provide the required support for all parents1920 NICUs need to be flexible enough to provide parents with a range of forms of support to choose from
The increased understanding of the strains that parents of sick neonates have to deal with has also led to efforts to improve customary practices in NICUs Family-centred care focuses on infants and their needs and attempts to redefine the relationship between parents and caregivers These practices strive to provide parents with support during their infantrsquos illness by focusing on freely sharing information and on the collaboration between parents and hospital staff Family-centred care has been found to be associated with several beneficial outcomes including improved parental satisfaction increased parental comfort staff satisfaction and decreased parental stress18 Research is already examining these practices and questioning how these can be improved further Such research reflects the increasing effort focused on lsquohumanizingrsquo the environment in NICUs in order to make parents feel more comfortable about spending time with their infants
PaeDiaTrics anD cHilD HealTH 184 19
Conclusion
Surprisingly few interventions have prioritized the provision of emotional support for parents of sick neonates or accounted for the changing needs and wishes of parents over the course of their infantrsquos care Large-scale supportive education-based inter-ventions have been shown to be effective in reducing parental distress However the feasibility and sustainability of such pro-grammes should also be considered Programmes which require significant additional resources can be expensive and there are also issues of training and quality control Interventions which require significant input from parents may also place additional burdens on families making them potentially less accessible to those most at risk Arguably the aim should be to explore ways of providing acceptable and effective informational support which could be complemented by emotional support from health professionals and from other parents in the unit Increasingly studies are exploring the use of computers and multimedia as an engaging flexible and cost-effective method of targeting indi-vidual needs and providing support and information Such com-puter-based and interactive multimedia interventions have been found to be successful with a range of patient groups and could therefore be examined as a complementary method of providing informational support to families with sick neonates
REfEREnCEs
1 Glazebrook c Marlow n israel c et al randomised trial of a
parenting intervention during neonatal intensive care Arch Dis Child
Fetal Neonatal Ed 2007 92 F438ndash443
2 singer lT salvator a Guo s collin M lilien l Baley J Maternal
psychological distress and parenting stress after the birth of a very
low-birth-weight infant JAMA 1999 281 799ndash805
3 shaw rJ Deblois T ikuta l Ginzburg K Fleisher B Koopman c
acute stress disorder among parents of infants in the neonatal
intensive care nursery Psychosomatics 2006 47 206ndash212
4 Hopper a sources of stress for parents of a sick neonate a
literature review Pediatr Nurs 2000 30 29ndash32
5 Davis l edwards H Mohay H wollin J The impact of very
premature birth on the psychological health of mothers Early Hum
Dev 2003 73 61ndash70
6 Bernazzani O saucier J-F David H Borgeat F Psychosocial
predictors of depressive symptomatology level in postpartum
women J Affect Disord 1997 46 39ndash49
7 Field T infants of depressed mothers Infant Behav Dev 1995 18
1ndash13
8 Kaplan Ps Bachorowski J-a Zarlengo-strouse P child-directed
speech produced by mothers with symptoms of depression fails
to promote associative learning in 4-month-old infants Child Dev
1999 70 560ndash570
9 ward K Perceived needs of parents of critically ill infants in
a neonatal intensive care unit (nicU) Pediatr Nurs 2001 27
281ndash286
10 lai Hl chen cJ Peng Tc et al randomized controlled trial of music
during kangaroo care on maternal state anxiety and preterm infantsrsquo
responses Int J Nurs Stud 2006 43 139ndash146
8 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
11 Tallandini Ma scalembra c Kangaroo mother care and mother-
premature infant dyadic interaction Infant Ment Health J 2006 27
251ndash275
12 Ohgi s Fukuda M akiyama T Gima H effect of an early intervention
programme on low birthweight infants with cerebral injuries
J Paediatr Child Health 2004 40 689ndash695
13 Kaaresen Pi ronning Ja Ulvund se Dahl lB a randomized
controlled trial of the effectiveness of an early-intervention program
in reducing parenting stress after preterm birth Pediatrics 2006
118 e9ndash19
14 Melnyk BM Feinstein nF alpert-Gillis l et al reducing premature
infantsrsquo length of stay and improving parentsrsquo mental health
outcomes with the creating opportunities for parent empowerment
(cOPe) neonatal intensive care unit program a randomized
controlled trial Pediatrics 2006 118 e1414ndash1427
15 Jotzo M Poets cF Helping parents cope with the trauma of
premature birth an evaluation of a trauma-preventive psychological
intervention Pediatrics 2005 115 915ndash919
16 Pearson J andersen K evaluation of a program to promote positive
parenting in the neonatal intensive care unit Neonatal Netw 2001
20 43ndash48
17 roman l lindsay J Boger r et al Parent-to-parent support
initiated in the neonatal intensive care unit Res Nurs Health 1995
18 385ndash394
18 Meyer ec coll cTG lester BM Boukydis cFZ McDonough sM Oh w
Family-based intervention improves maternal psychological well-
being and feeding interaction of preterm infants Pediatrics 1994
93 241ndash246
PaeDiaTrics anD cHilD HealTH 184 19
19 Preyde M ardal F effectiveness of a parent ldquobuddyrdquo program for
mothers of very preterm infants in a neonatal intensive care unit
CMAJ 2003 168 969ndash973
20 Hurst i One size does not fit all Parentsrsquo evaluations of a support
program in a newborn intensive care nursery J Perinat Neonatal
Nurs 2006 20 252ndash261
Practice points
bull Parents of sick neonates experience significant distress and
exhibit higher levels of stress anxiety and depression than
parents of healthy infants
bull educational support emotional support and increased
motherndashinfant contact have been shown to promote maternal
well-being
bull emotional support for fathers has been largely neglected in
the research literature
bull Parents benefit from a choice of supportive facilities which
could include face-to-face sessions with health professionals
telephone support hospital visitation parent-to-parent
support and unit-based group support meetings
bull Parentsrsquo support needs can change during their infantrsquos
hospitalization and not all parents want or benefit from the
provision of additional information and emotional support in
the neonatal unit
9 copy 2008 elsevier ltd all rights reserved
Personal Practice
When should enteral feeds be started in preterm infantsnicholas D embleton
AbstractPaediatricians are regularly faced with the question of when best to start
enteral feeds in preterm infants this is important as longer term out-
come may be compromised by sub-optimal nutrition in early life clinical
factors that may affect the decision to start and the risk and benefits
are discussed
Keywords breast milk feeding nutrition parenteral nutrition
Key points in the history
Alice is lsquonutritionally vulnerablersquo and whilst this may not be immediately apparent it will affect her long term outcome Her energy stores are extremely limited and consist primarily of pro-tein She has less than 5 fat and little energy associated with stored glycogen She is losing about 1 gkgd protein equivalent so she needs at least that and a minimum of 50ndash60 kcalkg of energy just to maintain the status quo let alone grow
Her weight is on the 25th centile Review of any antenatal his-tory may reveal whether fetal growth was normal Fetal growth retardation can occur with a weight greater than 10th centile The presence of antenatal absent or reversed end diastolic flow in the umbilical artery indicates poor gut blood flow This increases the risk of necrotizing enterocolitis (NEC) and might suggest a more cautious approach to starting feeds1
She has no important cardiovascular problems but if she were hypotensive gut blood flow may be low There is no umbilical
Nicholas D Embleton BSC (Hons) MBBS (Hons) MD FRCPCH is Consultant in
Neonatal Medicine at Newcastle Neonatal Service Royal Victoria
Infirmary Newcastle upon Tyne NE1 4LP UK
Should you start feeds at a day of age
alice was born following spontaneous labour at 30 weeksrsquo
gestation she weighed 1300 g and is now 18 h old she was
briefly ventilated and then extubated to continuous positive
airway pressure 12 h ago in 35 oxygen she has had caffeine
citrate but still has intermittent episodes of self-correcting
apnoea she was commenced on iv 10 dextrose but this was
replaced by a parenteral amino acid solution (referred to as
lsquotPnrsquo) along with intralipid at 0900 this morning serum glucose
is 11 mmoll and blood pressure is 42 systolic
PaeDiatrics anD cHilD HealtH 184 20
arterial catheter in situ but there is no good evidence that this should delay the decision to start feeds Her glucose is high but this is quite common in a baby like this Could this be a sign of sepsis Caffeine does not affect the incidence of NEC2 The great-est risk factor for NEC in this case is prematurity
What else might be found on examination
Up until 24 h ago she was swallowing large amounts of amniotic fluid What will have changed since then
General examination should confirm peripheral perfusion lsquogestaltrsquo view (does she look lsquowellrsquo) and cardiovascular status lsquoBowel soundsrsquo are not usually helpful
The most important variable likely to affect gut perfusion is the arterial duct Precordial lsquoheaversquo and a loud murmur are sug-gestive but it is possible to have a significant ductal shunt in a baby with a normal examination Cardiac ultrasound will con-firm this diagnosis It might be better to treat a large shunt first with indometacin and to delay starting feeds for a further 24 h
It is not possible to assess gut perfusion clinically but normal perfusion elsewhere (adequate urine output usually indicates adequate renal perfusion) would be reassuring Most preterm babies have a few abdominal lsquoloopsrsquo visible but a distended abdomen with many palpable loops suggests ileus This might be secondary to sepsis or poor gut blood flow Preterm babies do not pass much meconium in the first 24ndash48 h
Balance of risks between starting and withholding feeds
Alice requires 35ndash4 gkgd of protein and 120 kcalkgd to grow3 This will initially be provided parenterally Delaying feeds increases the risk of gut villous atrophy and prolongs the need for lsquototal parenteral nutrition (TPN)rsquo TPN requires intravenous access and so increases the risk of sepsis and when prolonged use is required combined with the lack of enteral feeding may result in hepatic impairment
Delaying feeds may allow a gut that has been chronically under-perfused to re-establish more normal perfusion although normal gut endocrine function digestive enzyme upregulation and motility require a source of intraluminal nutrients1 A recent study suggested benefit from delaying the introduction of feeds4 but methodologi-cal problems exist5 Although a Cochrane meta-analysis suggested no benefit only two studies were included6 A large UK-based trial is examining the effect of early or late feeding in preterm infants who were born growth retarded following identification of antena-tal absent or reversed end diastolic flow in the umbilical artery7
When starting feeds what volume should be used
There are no good data to guide this decision We start with 24 mlkg (1 mlkgh) and then increase by this amount each day Most babies achieve full enteral feeds (ge150 mlkgd) by a week of age Feeding guidelines improve the outcome8 Measure-ment or assessment of gastric aspirates is not consistently useful in predicting subsequent feeding intolerance or development of NEC Aspirate volumes equivalent to or sometimes greater than the amount given in the preceding 1ndash2 h are usually normal Most aspirates have a greenish colour Thick bloody or intensely bile-stained aspirates require detailed assessment
0 copy 2008 elsevier ltd all rights reserved
Personal Practice
What else affects decisions and outcome
Feeding success is affected by sepsis and NEC Scrupulous atten-tion should be paid to hand washing and intravenous access and blood sampling should be minimized There is no good evidence to support the routine use of pro-kinetic agents or H2 blockers
The most important clinical intervention affecting the occur-rence of NEC is the use of breast milk9 All efforts should be directed at persuading parents of the benefits and supporting the process Some clinicians delay starting feeds for a further 24 h whilst expressed breast milk becomes available Donor breast milk might be equally efficacious10
RefeRenceS
1 Dorling J Kempley s leaf a Feeding growth restricted preterm
infants with abnormal antenatal Doppler results Arch Dis Child Fetal
Neonatal Ed 2005 90 F359ndash363
2 schmidt B roberts rs Davis P et al caffeine therapy for apnea of
prematurity N Engl J Med 2006 354 2112ndash2121
PaeDiatrics anD cHilD HealtH 184 20
3 embleton nD Pang n cooke rJ Postnatal malnutrition and growth
retardation an inevitable consequence of current recommendations
in preterm infants Pediatrics 2001 107 270ndash273
4 Berseth cl Bisquera Ja Paje VU Prolonging small feeding volumes
early in life decreases the incidence of necrotizing enterocolitis in
very low birth weight infants Pediatrics 2003 111 529ndash534
5 Menon G Boyle eM embleton nD et al introduction of enteral
feeds in preterm infants Pediatrics 2004 114 327ndash328
6 Kennedy Ka tyson Je chamnanvanikij s early versus delayed
initiation of progressive enteral feedings for parenterally fed low
birth weight or preterm infants Cochrane Database Syst Rev 2000
cD001970
7 wwwnpeuoxacukadept
8 Patole sK de Klerk n impact of standardised feeding regimens on
incidence of neonatal necrotising enterocolitis a systematic review
and meta-analysis of observational studies Arch Dis Child Fetal
Neonatal Ed 2005 90 F147ndash151
9 lucas a cole tJ Breast milk and neonatal necrotising enterocolitis
Lancet 1990 336 1519ndash1523
10 Boyd ca Quigley Ma Brocklehurst P Donor breast milk versus
infant formula for preterm infants systematic review and meta-
analysis Arch Dis Child Fetal Neonatal Ed 2007 92 F169ndash175
1 copy 2008 elsevier ltd all rights reserved
self-assessment
Case 1A term male infant born to consanguineous parents is assessed at 24 h of age due to poor feeding profuse yellow watery diar-rhoea and irritability He weighed 32 kg at birth and delivery was uneventful There was no polyhydramnios He has been breastfed since birth On examination he is pale with a non-tender but distended abdomen and reduced bowel sounds His weight is 275 kg and he looks dehydrated Examination is otherwise normal
Initial investigations (normal values in parentheses) showed
sodium 149 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 65 mmollitre (25ndash75)
creatinine 147 μmollitre (40ndash110)
chloride 119 mmollitre (95ndash105)
haemoglobin 172 gdl (140ndash200)
White blood cell count 80 times 109litre (100ndash260)
Platelet count 302 times 109litre (150ndash400)
arterial blood gas
ph 720 (730ndash745)
PcO2 23 kPa (46ndash60)
Bicarbonate 68 mmollitre (220ndash260)
Base excess minus186 mmollitre (minus20 to +20)
lactate 59 mmollitre (06ndash24)
An abdominal X-ray shows distended bowel loops with no intramural thickening or pneumoperitoneum (Figure 1)
He was given nil by mouth and received intravenous fluids and antibiotics His dehydration improved but the metabolic acidosis and diarrhoea persisted despite receiving no enteral feeds and the commencement of total parenteral nutrition Blood and stool cultures were negative
1 Which of the following best describes these results Choose ONE answer ONLY from the followingA Hypernatraemia hyperchloraemic metabolic acidosis
with increased anion gapB Hypernatraemia hyperchloraemic metabolic acidosis
with normal anion gap
Manish Sadarangani BM BCh MA MRCPCH is Clinical Research Fellow
at the Department of Paediatrics University of Oxford Centre for
Clinical Vaccinology and Tropical Medicine Churchill Hospital
Oxford OX3 7LJ UK
Shabna Rajapaksa MB BChir MA MRCPCH is Specialist Registrar in
Paediatrics at the Paediatric Intensive Care Unit John Radcliffe
Hospital Oxford OX3 9DU UK
Nicholas Mann MD FRCP FRCPCH DCH is Consultant Paediatrician at the
Department of Paediatrics Royal Berkshire Hospital Reading RG1
5AN UK
self-assessment
C Hypernatraemic dehydration and compensated metabolic acidosis
D Acute renal failureE Renal tubular acidosis
2 What is the likely diagnosis Choose ONE answer ONLY from the followingA Hirschsprung disease ndash long segmentB Cystic fibrosis with meconium ileusC Microvillus inclusion diseaseD Cowrsquos milk protein intoleranceE Lactose intolerance
3 What is the investigation of choice Choose ONE answer ONLY from the followingA Rectal biopsy with staining for acetylcholine receptorsB Immunoreactive trypsinC Gastrointestinal endoscopy and biopsyD Stool microscopy and cultureE Stool reducing substances
Case 2A 4-year-old boy presents with a 3 d history of jaundice and a florid rash He has had orange urine and there is no change in his stool colour His family originate from Kosovo and have lived in the UK for the last 8 years He has never left the UK There is no history of blood transfusion or sex-ual abuse The grandmother was recently diagnosed with hepatitis B
On examination he is well apyrexial and mildly jaundiced with cervical and axillary lymphadenopathy He has an exten-sive papular rash over the face extremities and trunk (Figure 2) There is 3 cm hepatomegaly with no splenomegaly or ascites Examination is otherwise normal
Figure 1 abdominal X-ray of baby
Paediatrics and child health 184 202 copy 2008 elsevier ltd all rights reserved
self-assessment
Initial investigations are as follows
haemoglobin 110 gdl (113ndash135)
White blood cell count 108 times 109litre (50ndash150)
Platelet count 278 times 109litre (150ndash400)
inr 10 (08ndash12)
aPt ratio 10 (08ndash13)
sodium 140 mmollitre (135ndash145)
Potassium 42 mmollitre (35ndash50)
Urea 56 mmollitre (25ndash75)
creatinine 65 μmollitre (45ndash120)
total bilirubin 66 μmollitre (0ndash15)
conjugated bilirubin 23 μmollitre (0ndash10)
alanine aminotransferase (alt) 2033 iUlitre (0ndash35)
alkaline phosphatase 987 iUlitre (71ndash234)
Gamma-glutamyl transferase (GGt) 870 iUlitre (0ndash51)
1 What is the name of this rash Choose ONE answer ONLY from the followingA Erythema multiformeB Erythema migransC GianottiminusCrosti syndromeD EczemaE Dermatitis herpetiformis
2 What is the most likely diagnosis Choose ONE Answer ONLY from the followingA Autoimmune hepatitisB Hepatitis BC Hepatitis DD Wilson diseaseE Alpha-1 antitrypsin deficiency
3 What is the best means of management Choose ONE answer ONLY from the followingA Isolation until the jaundice disappearsB ImmunosuppressionC Copper chelating agents and genetic counsellingD Patient and family education with consideration of
antiviral agentsE Liver transplantation
Case 3A 10-month-old boy presents with 3 weeks of vomiting and constipation ndash he is passing hard stools every 2ndash3 days He has fallen from the 9th to below the 04th centile in the last 6 weeks He passed meconium within the first 24 h of life On examina-tion he looks pale and there are some dysmorphic features ndash a short nose long philtrum and wide mouth He has normal heart sounds with a grade 3 ejection systolic murmur loudest at the upper right sternal edge Examination is otherwise normal
Initial investigations are as follows
haemoglobin 91 gdl (113ndash141)
total white blood cell count 124 times 109litre (60ndash170)
Platelet count 407 times 109litre (150ndash400)
sodium 144 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 78 mmollitre (25ndash75)
creatinine 78 μmollitre (45ndash120)
albumin 52 glitre (35ndash50)
corrected calcium 384 mmollitre (238ndash263)
Phosphate 167 mmollitre (099ndash157)
1 What is the most likely diagnosis Choose ONE answer ONLY from the followingA HyperparathyroidismB Acute leukaemiaC Williams syndromeD Hypervitaminosis DE Familial hypocalciuric hypercalcaemia
2 Which investigation would be most useful in establishing the diagnosis Choose ONE answer ONLY from the followingA Intact parathyroid hormone assayB Blood filmC Fluorescent in-situ hybridization for 7q1123 deletionD 25-hydroxyvitamin D assayE Urine calciumcreatinine ratio
3 Which of the following treatments would not be suitable for this patient Choose ONE answer ONLY from the followingA Low calcium dietB Normal saline infusionC FurosemideD CorticosteroidsE Bisphosphonates
Case 4A 10-week-old girl presents with a 2-day history of poor feed-ing Her mother has been concerned about weakness since birth She only has a flicker of movement in the arms none in the legs and has a weak cry She has been passing urine and opening her bowels normally She was born at full term by normal delivery and did not require any resuscitation at birth Normal fetal movements were felt antenatally and there was no polyhydramnios She is the first child of non- consanguineous parents and there is no significant family his-tory On examination she is alert and fixing and following appropriately She has a weak cry and a weak suck There is reduced central and peripheral tone with marked head lag
Figure 2 rash found on examination
Paediatrics and child health 184 203 copy 2008 elsevier ltd all rights reserved
self-assessment
Muscle power is grade 3 out of 5 in the arms and legs There is no muscle or tongue fasciculation and she has absent reflexes throughout The remainder of the examination is normal
Electromyogram shows irregular polyphasic motor unit potentials with marked instability consistent with a dener-vating and re-innervating process (Figure 3)
1 Which of the following additional investigations may be helpful Choose ONE answer ONLY from the followingA Nerve conduction studiesB Creatine kinase assayC Muscle biopsyD SMN1 gene analysisE All of the above
2 What is the most likely cause of this childrsquos symptoms Choose ONE answer ONLY from the followingA Congenital myotonic dystrophyB Duchenne muscular dystrophyC PraderminusWilli syndromeD Spinal muscular atrophyE Mitochondrial myopathy
3 What is the mode of inheritance of this disease Choose ONE answer ONLY from the followingA X-linked recessiveB Autosomal recessiveC Autosomal dominantD MitochondrialE Sporadic
Case 5A 13-year-old girl presents with a 3-week history of fever up to 40degC night sweats and headache She has a reduced appetite with some weight loss She has no other specific symptoms She was on holiday in China 7 months ago On examination she looks well and has a temperature of 387degC There is no lymphadenopathy and no rashes Examination is entirely normal
Results of investigations are as follows
haemoglobin 126 gdl (120ndash160)
total white blood cell count 132 times 109litre (43ndash108)
neutrophil count 115 times 109litre (25ndash75)
Platelet count 244 times 109litre (150ndash400)
Blood film neutrophilia with left shift
erythrocyte sedimentation rate 63 mmh (1ndash20)
c-reactive protein 219 mglitre (0ndash5)
Blood culture Streptococcus intermedius
from anaerobic bottle only
csf culture negative
Magnetic resonance imaging (MRI) of the brain shows acute frontal sinusitis with a large intracranial frontal extra-dural empyema (Figure 4)
1 Which of the following would be appropriate management Choose ONE answer ONLY from the followingA A 12-week course of intravenous antibioticsB Drainage of the frontal sinus followed by 2 weeks of
intravenous antibioticsC Drainage of the empyema followed by 2 weeks of
intravenous antibioticsD Drainage of the empyema and the frontal sinus
followed by 2 weeks of oral antibiotics
1151
1152
1153
1154
1155
1156
1157
1158
1159
1200
50ms 1mV
Figure 3 electromyogram recording from the patient Figure 4 Parasagittal section from mri scan of patient
Paediatrics and child health 184 204 copy 2008 elsevier ltd all rights reserved
self-assessment
E Drainage of the empyema and the frontal sinus followed by 8 weeks of intravenous antibiotics
2 Streptococcus intermedius is a potential pathogen in which of the following infections Choose ONE answer ONLY from the followingA Liver abscessB Urinary tract infectionC MeningitisD Thoracic empyemaE Pneumonia
3 Which of the following statements regarding lsquopyrexia of unknown originrsquo in children is false Choose ONE answer ONLY from the followingA Malignancy is the underlying pathology in 5ndash15 of
casesB An aetiology will be found in over 90 of casesC The most common cause is infectionD A rheumatological cause is found in 10ndash20 of casesE Familial Mediterranean fever can occur in children of
non-Mediterranean ethnicity
Answers
Case 11 AThe anion gap is a useful tool to differentiate the causes of a metabolic acidosis It is calculated by the equation
Anion gap = [Na K ] [Cl HCO ]3+ + minus minus+ minus +
It represents the effect of unmeasured anions on the plasma pH and is normally 10ndash18 mmollitre
2 CMicrovillus inclusion disease is a severe autosomal recessive enteropathy that is typically apparent within hours or days after birth It is the second most common cause of protracted diarrhoea in the newborn after infectious causes It is characterized by severe yellow watery diarrhoea and malabsorption due to hypoplasia andor atrophy of the villi of the small intestine secondary to an inherited defect in the brush border membrane This results in severe dehydration malnutrition and metabolic acidosis due to bicarbonate loss from the gut
3 CDiagnosis of microvillus inclusion disease is made on small bowel biopsy Electron microscopy findings are of intracellular brush border inclusions and densely packed apical cytoplasmic vesicular bodies indicating microvillous atrophy There is no cure Treatment is supportive with total parenteral nutrition and consideration of small bowel transplantation
Further reAding
Goulet O ruemmele f causes and management of intestinal failure
in children Gastroenterology 2006 130(suppl 1) s16ndash28
rhoads Jm Vogler rc lacey sr et al microvillus inclusion disease
In vitro jejunal electrolyte transport Gastroenterology 1991
100 811ndash817
Case 21 CGianottindashCrosti syndrome is a distinct self-limiting rash commonly associated with viral infections in children between 2 and 6 years of age It presents as multiple pink to redminusbrown papules or papulovesicles which may be pruritic and can become confluent Gianotti and Crosti initially described the exanthema as associated with hepatitis B virus and they termed it papular acrodermatitis of childhood It can occur in several viral diseases eg hepatitis A B and C coxsackie viruses and cytomegalovirus
2 BHepatitis is a syndrome characterized by inflammation or injury of liver cells which may develop into cell necrosis and subsequently fibrosis andor cirrhosis Biochemically there are raised liver enzymes The degree of transaminase elevation does not correlate with the severity of the disease process Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of viral hepatitis
3 DHepatitis B infection is transmitted via blood sexually or vertically Infection may be acute or chronic Diagnostic markers are the presence of surface antigen (HBsAg) and HBV DNA The presence of e antigen (HBeAg) indicates high infectivity Infected newborns have a 95 risk of becoming carriers this risk decreases with infection acquired later in childhood Approximately 15ndash25 of HBV carriers will die from cirrhosis or hepatocellular carcinoma Extrahepatic findings are more common in older children and include membranous glomerulonephritis and GianottiminusCrosti syndrome Fulminant hepatic failure occurs in severe cases resulting in persistent jaundice encephalopathy and coagulopathy Management includes counselling family members monitoring for ongoing liver disease and consideration of antiviral therapy
Further reAding
Brandt O abeck d Gianotti r Burgdorf W Gianotti crosti
syndrome J Am Acad Dermatol 2006 54 136ndash145
slowik mK Jhaveri r hepatitis B and c viruses in infants and
young children Semin Pediatr Infect Dis 2005 16 296ndash305
Case 31 CHypercalcaemia is uncommon in infancy The most common symptoms in this age group are irritability vomiting and constipation It may be a manifestation of Williams syndrome vitamin D or calcium excess as well as disorders associated with reduced bone formation such as hypophosphatasia or increased bone resorption such as malignancy Occasionally
Paediatrics and child health 184 205 copy 2008 elsevier ltd all rights reserved
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-
SympoSium neonatology
in the human fetus and newborn and etiology of the respiratory
distress syndrome Pediatr Res 1972 6 81ndash99
14 Vohra S Roberts RS Zhang B Janes m Schmidt B Heat loss
prevention (Help) in the delivery room a randomised controlled
trial of polyethylene occlusive skin wrapping in very preterm infants
J Pediatr 2004 145 750ndash753
15 owen CJ Wyllie Jp Determination of heart rate in babies at birth
Resuscitation 2004 60 213ndash217
16 orsquoDonnell Cp Kamlin Co Davis pg Carlin JB morley CJ Clinical
assessment of infant colour at delivery Arch Dis Child Fetal
Neonatal Ed 2007 92 F465ndashF467
17 international liaison Committee on Resuscitation part 13 neonatal
Resuscitation guidelines Circulation 2005 112(suppl 24)
iV188ndashiV195
18 leone ta Rich W Finer nn neonatal intubation Success of
pediatric trainees J Pediatr 2005 146 638ndash641
19 orsquoDonnell Cp Kamlin Co Davis pg morley CJ endotracheal
intubation attempts during neonatal resuscitation success
rates duration and adverse effects Pediatrics 2006 117
e16ndash21
20 Repetto Je Donohue pa-CpK Baker SF Kelly l nogee lm use of
capnography in the delivery room for assessment of endotracheal
tube placement J Perinatol 2001 21 284ndash287
21 gandini D Brimacombe JR neonatal resuscitation with laryngeal
mask airway in normal and low birth weight infants Anesth Analg
1999 89 642ndash643
22 esmail n Saleh m ali a laryngeal mask airway versus endotracheal
intubation for apgar score improvement in neonatal resuscitation
Egypt J Anesthiol 2002 18 115ndash121
23 Wiswell te gannon Cm Jacob J et al Delivery room management
of the apparently vigorous meconium-stained neonate results of
the multicenter international collaborative trial Pediatrics 2000
105 1ndash7
24 Vain ne Szyld eg prudent lm Wisewell te aguilar am Vivas ni
oropharyngeal and nasopharyngeal suctioning of meconium-stained
neonates before delivery of their shoulders multicentre randomised
controlled trial Lancet 2004 364 597ndash602
25 Bjorklund lJ ingimarsson J Curstedt t larsson a Robertson B
Werner o lung recruitment at birth does not improve lung function
in immature lambs receiving surfactant Acta Anaes Scand 2001 45
986ndash993
26 Bjorklund lJ ingimarsson J Curstedt t et al manual ventilation
with a few large breaths at birth compromises the therapeutic effect
of subsequent surfactant replacement in immature lambs Pediatr
Res 1997 42 348ndash355
paeDiatRiCS anD CHilD HealtH 184 17
27 taskar V John J evander e Robertson B Jonson B Surfactant
dysfunction makes lungs vulnerable to repetitive collapse and re-
expansion Am J Respir Crit Care Med 1997 155 313ndash320
28 muscedere Jg mullen JB gan K Slutsky aS tidal ventilation at low
airway pressures can augment lung injury Am J Respir Crit Care Med
1994 149 1327ndash1334
29 nilsson R grossman g Robertson B Bronchiolar epithelial lesions
induced in the premature rabbit neonate by short periods of artificial
ventilation Acta Pathol Microbiol Scand 1980 88 359ndash367
30 probyn me Hooper SB Dargaville pa et al positive end expiratory
pressure during resuscitation of premature lambs rapidly improves
blood gases without adversely affecting arterial pressure Pediatr
Res 2004 56 198ndash204
31 Wood Fe morley CJ Dawson Ja et al improved techniques
reduce face mask leak during simulated neonatal resuscitation
study 2 Arch Dis Child Fetal Neonatal Ed in press doi101136
adc2007117788
32 tan a Schulz a orsquoDonnell CpF Davis pg air versus oxygen for
resuscitation of infants at birth Cochrane Database Syst Rev 2004
(3) CD002273
33 Davis pg tan a orsquoDonnell Cp Schulze a Resuscitation of newborn
infants with 100 oxygen or air a systematic review and meta-
analysis Lancet 2004 364 1329ndash1333
34 Dawes g Fetal and neonatal physiology Chicago year Book
publisher 1968 p 141ndash159
35 Ziino aJa Davies mW Davis pg epinephrine for the resuscitation
of apparently stillborn or extremely bradycardic newborn infants
Cochrane Database Syst Rev 2003 (2) CD003849
36 Wyckoff m garcia D margraf l perlman J laptook a Randomized
trial of volume infusion during resuscitation of asphyxiated neonatal
piglets Pediatr Res 2007 61 415ndash420
Practice points
bull Resuscitation at birth is different from that at all other times
of life
bull a standard approach can be applied to most newborn
resuscitation
bull guidelines are based on a rigorous evaluation of evidence
where possible
bull evidence is sparse but evolving
bull most preterm babies require stabilization rather than
resuscitation
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Acidndashbase physiology and blood gas interpretation in the neonateSusern tan
morag Campbell
Abstractacidndashbase balance describes the complex processes that work to main-
tain a stable extracellular pH for optimal cellular function the process
of balancing the production and neutralization of tissue acid provides a
great challenge for newborn infants who have significantly higher rates
of acid production than adults Factors which help maintain a stable
acidndashbase balance include buffers the respiratory system and renal sys-
tem Both intracellular and extracellular buffers resist changes in pH
the most important extracellular buffer system for maintaining stable
pH is the bicarbonate system in response to acidosis or alkalosis the
respiratory system balances the production of acid with the clearance
of Co2 by altering respiratory rate the kidneys provide a delayed but
sustained response to pH imbalance by excreting either acidic or alkaline
urine in response to systemic acidosis and alkalosis respectively in sick
premature infants these systems have a limited capacity completely to
control pH this review discusses the physiology of the three systems
which control acidndashbase balance patterns of clinical abnormalities in
acidndashbase status and their underlying causes are discussed We present
a systematic approach to blood gas analysis and interpretation in new-
born infants
Keywords acidosis alkalosis bicarbonate bloodndashgas analysis
metabolic pH
Introduction
Blood gas analysis is a routine procedure performed on newborn babies receiving respiratory support in the neonatal intensive care The combination of invasive and non-invasive assessment of ventilation and oxygenation enables clinicians appropriately to modify respiratory care according to each individual babyrsquos rapidly changing clinical status
Understanding the fundamentals of acidndashbase balance helps us to use blood gas analysis not only to assess respiratory sta-tus but also to provide information on metabolic status and the adequacy of tissue perfusion
Susern Tan MBBS MRCP is Clinical Fellow at the Neonatal Intensive Care
Unit 6th Floor North Wing St Thomasrsquo Hospital London SE1 7EH UK
Morag Campbell MBChB MRCP is Consultant Neonatologist at the
Neonatal Intensive Care Unit 6th Floor North Wing St Thomasrsquo
Hospital London SE1 7EH UK
paeDiatRiCS anD CHilD HealtH 184 17
What is understood by acid-base balance
Acidndashbase balance refers to the complex physiological processes used by the body to maintain a stable extracellular pH1 A serum pH within the range of 735ndash745 provides the ideal environment for cellular metabolism Maintaining a stable pH is critical as the metabolic activity of proteins is pH dependent and small changes in hydrogen ion (H+) concentration can potentially alter physio-logical function
Acids are substances that yield free H+ in solution while a base accepts H+ and in solution combines with an acid to neu-tralize it In the normal metabolic state H+ are continuously pro-duced and neutralized to maintain a steady pH balance12 The rate of H+ production is two to three times higher in neonates because of their rapid growth rates and increased acid production from protein turnover and bone mineralization The challenge of maintaining a stable pH through processing and neutralizing H+ is therefore greatest in newborn infants
Using exact values of H+ concentration to assess acidndashbase status is cumbersome and it is more commonly expressed as pH defined by the equation
pH = minuslog H+
Maintaining acidndashbase balance
The balance between production and excretion of acids in the body is controlled by buffer systems which have an immediate effect and by the respiratory and the renal systems
Buffer systemsBuffer solutions resist change in pH when acid or alkali is added due to their capacity to absorb or give up H+ The three main buffer systems in the body are the bicarbonate phosphate and protein systems1ndash3 The protein and phosphate buffer systems are intracellular and act as lsquosinksrsquo for extracellular H+ which are exchanged with intracellular potassium (K+) and sodium ions (Na+) In an acute metabolic acidosis hyperkalaemia may develop due to this H+ exchange4
The bicarbonate buffer system is extracellular and consists of a mixture of carbonic acid (H2CO3) and sodium bicarbon-ate (NaHCO3) This buffer system helps maintain a stable pH by soaking up excess H+ with HCO3
minus which in solution forms carbonic acid (H2CO3) Carbonic acid is a weak acid and readily dissociates to give CO2 which is transported in dissolved form to the lungs for excretion
H+ + HCO3minus harr H2CO3 harr H2O + CO2
The bicarbonate system therefore completes the neutraliza-tion of excess H+ and a stable plasma pH is maintained The relationships between pH HCO3
minus and CO2 in this system are described by the HendersonndashHasselbalch equation15
pH = 61 + log HCO3minus003 times CO2
where 61 is the log of the dissociation coefficient of carbonic acid and 003 the solubility of CO2 in plasma Buffers are most potent when there are equal amounts of H+ and HCO3
minus in solution The
2 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
bicarbonate system is not a potent buffer however as HCO3minus
and CO2 are readily altered by the body this system plays a very powerful role in pH homeostasis15
Respiratory regulationThe respiratory system adapts within minutes to hours as part of the acute response to acidosis This system modifies pH by balancing production of H+ with ventilatory clearance of CO2
H+ directly stimulates chemoreceptors in the respiratory cen-tre of the brainstem producing an increase in respiratory rate26 The response to respiratory acidosis is very rapid as CO2 easily diffuses across the bloodndashbrain barrier however in metabolic acidosis compensation is delayed until plasma bicarbonate fully equilibrates with cerebrospinal fluid (CSF) bicarbonate There is an inverse relationship between alveolar ventilation and partial pressure of dissolved carbon dioxide (PaCO2) a reduction in alveolar ventilation raises PaCO2 and decreases pH Changes in pH therefore affect alveolar ventilation and conversely changes in alveolar ventilation cause significant changes in pH
Renal regulationThe kidneys provide a delayed but sustained response to acidndashbase imbalances by excreting either acidic or alkaline urine In full-term and preterm babies the capacity for acid excretion and bicarbonate reabsorption is reduced as glomerular filtration rates are low and tubular function immature7 Renal function matures with gestation postnatal age and glucocorticoid and thyroid hormones78 Due to their limited capacity to preserve HCO3
minus newborn infants have lower serum bicarbonate levels and are predisposed to acidosis7
Bicarbonate is not effectively reabsorbed due to its size and electrical charge Instead intraluminal HCO3
minus combines with secreted H+ in tubular luminal fluid to produce carbonic acid which dissociates to give H2O and CO2 This CO2 diffuses into tubular cells combines with intracellular H2O and forms carbonic acid which liberates HCO3
minus and H+ HCO3minus is then
recovered to the circulation by exchange for chloride ions (Clminus) through the basal cell membrane247
Renal acid secretion occurs at all sites except the loop of Henle Primary active transport accounts for 5 and secondary for the remaining 95 of total H+ excretion Secondary trans-port involves an exchange between luminal Na+ and intracel-lular H+ Both ions bind to a membrane transport protein The Na+ concentration gradient between the tubular lumen and cells enables Na+ drag into the cell which generates energy to fuel active H+ excretion into the tubular lumen1ndash47
Quantifying acidosis
Standard base excess is a calculated value derived from PaCO2 and pH It is expressed as the mmollitre of base above or below normal buffer bases required to correct the pH to 74 at a PaCO2 of 40 mmHg A negative base excess or base deficit indicates an acidosis while a positive base excess indicates a relative alkalosis15
Anion gap is the measured difference between anions and cations in the blood
Anion gap = (Na+ + k+) minus (HCO3+Clminus)
paeDiatRiCS anD CHilD HealtH 184 17
Calculation of the anion gap enables clinicians better to define the underlying cause of a metabolic acidosis9 The common causes of an increased anion gap acidosis in neonates include lactic acidosis due to tissue hypoperfusion and hypoxia it may also be seen with certain inborn errors of metabolism and in uraemia910 The anion gap can help distinguish between the rela-tively benign non-anion gap hyperchloraemic acidosis seen in premature infants and a pathological lactic acidosis due to poor end-organ perfusion1011
Strong ion theory
Stewart described a complex acidndashbase model which proposed that H+ concentration results from the dissociation of water which is influenced by PaCO2 the strong ion difference and plasma weak acids12
Strong ions are ions that dissociate at normal body pH and include Na+ K+ and Clminus Weak acids in plasma which contrib-ute include albumin inorganic phosphate and plasma proteins their concentrations do not change with pH and are therefore a constant The effect of these factors and other unmeasured tissue ions on acidndashbase status can be quantified by the calculation of the strong ion gap (SIG)112 In the neonatal unit it is perhaps more important that we consider how principles of this model may relate to acidndashbase status rather than fully to quantify the SIG Theoretically low albumin and phosphate levels which fre-quently occur in premature infants by reducing the concentra-tion of weak acids can produce a relative alkalosis while high phosphate levels in renal failure may contribute to acidosis
Tissue oxygenation
Oxygenation is closely linked to acidndashbase status as optimal cel-lular function requires oxygen to fuel aerobic metabolism and produce energy In hypoxic conditions anaerobic metabolism predominates which is energy inefficient and results in a lactic acidosis1011
Tissue oxygen availability is related to regional blood flow haemoglobin level and haemoglobin oxygen affinity Arterial blood gases measure the partial pressure of dissolved oxygen (PaO2) which represents a small component of total oxygen con-tent the majority being transported bound to haemoglobin The relationship between percentage haemoglobin saturation (SaO2) and PaO2 is described by the sigmoidal oxyhaemoglobin disso-ciation curve which enables us to relate the two measures to each other235 The affinity of haemoglobin for oxygen is altered by local tissue factors Increases in temperature H+ PaCO2 and 23-diphosphoglycerate (DPG) levels shift the oxyhaemoglobin dissociation curve to the right reducing affinity for oxygen Decreases in temperature H+ PaCO2 and 23-DPG levels shift the curve to the left increasing oxygen affinity1ndash35 In the body haemoglobin oxygen affinity continuously changes increasing in the lungs to enable efficient oxygen uptake and decreasing at tissue level to provide efficient oxygen delivery to metabolically active tissues
Avoiding both hypoxia and hyperoxia is important in the neo-natal unit as deleterious effects of hypoxia are seen in infants with pulmonary hypertension1314 while hyperoxia is associated with an increased incidence of retinopathy of prematurity1516
3 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Clinical acidndashbase imbalances
Clinical acidndashbase imbalances can be respiratory metabolic or a mixture of both These abnormalities may be corrected by the acidndashbase regulatory mechanisms in the body in an attempt to maintain normal pH (Figure 1)
Respiratory acidosisThis occurs when any disorder leads to decreased alveolar ventilation Common causes of respiratory acidosis are listed in Table 1 Reduced respiratory clearance of CO2 means more dissolved CO2 accumulates in the plasma leading to increased production of carbonic acid and H+ Through chemoreceptor stimulation respiratory acidosis rapidly alters ventilation in an attempt to reduce CO226 Chemoreceptor mediated ventila-tory increases may only partly adjust in premature infants with underlying lung disease In babies with a sustained respiratory acidosis eg in chronic lung disease then metabolic compen-sation occurs through increased renal excretion of H+ and reabsorption of HCO3
minus slowly restoring pH to around 80 of normal47
paeDiatRiCS anD CHilD HealtH 184 17
The management of PaCO2 levels in infants receiving mechan-ical ventilation has important clinical implications Premature babies have impaired cerebral autoregulation17 and adverse neurological sequelae are reported in association with high PaCO2 levels18ndash20 Ventilation strategies which advocate lsquoper-missive hypercarbiarsquo have been developed to minimize airways damage from mechanical ventilation21 Published data suggest pulmonary benefits however the safe level of PaCO2 remains to be defined in premature infants2021
Respiratory alkalosisThis occurs when more CO2 is excreted than is produced by the body Pathological conditions leading to respiratory alkalosis are rare Hyperventilation in the neonatal setting is often iatrogenic or may be due to disorders in brainstem control of breathing including hypoxicndashischaemic encephalopathy or primary central nervous system abnormalities (see Table 1)
If respiratory alkalosis is sustained it may be compensated for by reduced reabsorption of filtered bicarbonate Reported adverse associations of low PaCO2 include periventricular leuco-malacia and intraventricular haemorrhage1922
K+
H+
Overventilation
CO2 + H2O harr H2CO3 harr H+ + HCO3ndash
Bicarbonate Buffer
Intracellular Buffer
uarr H+ excretionuarr HCO3
ndash absorption
uarr buffered H+
(NH4+ H2PO4
ndash)uarr ventilation rate
RespiratoryAcidosis
MetabolicAcidosis
darr CO2and uarr pH
RespiratoryAlkalosis
MetabolicAlkalosis
darr H+ anduarr pH
darr ventilation rate
uarrCO2
and darr pH
darr H+ excretiondarr HCO3
ndash absorption
uarrH+ and
darr pH
Brain
Brain
Intracellular Buffer
H+
K+
Sepsis
HypoxiaRDS
Metabolismand growth
Diuretics
Airwayobstruction
Neuromuscularproblems
IEM
Gastric losses
+ +
ndash -
Renal BufferRespiratory Buffer
Figure 1 mechanisms for regulation of extracellular pH iem inborn errors of metabolism RDS respiratory distress syndrome
4 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Common causes of acidndashbase imbalances
pH PCO2 H2CO3 Base excess Common neonatal causes
Respiratory acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
uarr normal normal bull upper airway obstruction choanal atresia
pierre-Robin sequence
bull lung abnormalities respiratory distress
syndrome transient tachypneoa of
newborn pneumonia meconium aspiration
syndrome pulmonary hypoplasia
congenital pulmonary malformations
bull Central hypoventilation hypoxic-ischaemic
encephalopathy intracranial haemorrhage
bull neuromuscular insufficiency congenital
myopathies congenital neuropathies
bull iatrogenic inadequate ventilatory settings
Compensated lower limit
of normal
uarr uarr gt+3
metabolic acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
normal darr ltminus3 increased anion gap
bull lactic acidosis sepsis hypoperfusion
shock necrotizing enterocolitis
bull inorganic acidosis inborn errors of
metabolism renal failure
normal anion gap
bull increased gastrointestinal H2Co3 losses
ileostomy diarrhoea
bull Renal tubular acidoses
Compensated lower limit
of normal
darr darr ltminus3
Respiratory alkalosis Uncompensated gt 745 darr normal normal bull iatrogenic excessive ventilatory settings
bull Compensatory hyperventilation hypoxic-
ischaemic encephalopathy
Compensated higher limit
of normal
darr darr ltminus3
metabolic alkalosis Uncompensated gt 745 normal uarr gt+3 bull gastric losses vomiting non-replacement
of excessive nasogastric aspirates
bull thiazide and loop diuretics
bull Hypokalaemia
Compensated higher limit
of normal
uarr uarr gt+3
Table 1
Metabolic acidosisThis frequently affects infants in the neonatal unit and has many causes1011 (see Table 1) There may be overproduction of tissue acid impaired acid clearance gastrointestinal loss of bicarbonate or an exogenous increased acid load eg chloride total paren-teral nutrition (TPN) or albumin1ndash323
Calculation of the anion gap to distinguish an increased anion gap acidosis from a non-anion gap acidosis is important both for treatment and prognosis1011 Acidosis stimulates respiratory compensation but this is limited in unstable infants Similarly renal compensation with improved HCO3
minus conservation is con-strained by tubular immaturity Treatment of the acidosis should be directed at the underlying cause eg hypoxia hypotension or excess Clminus rather than by administration of base
Metabolic alkalosisThis is unusual in neonates and is most frequently seen in infants with chronic lung disease or heart failure who are receiving diuretics Diuretics cause alkalosis by increasing renal fluid and Na+ losses An active process to reabsorb Na+ occurs in tubule cells which through enhanced H+ secretion and HCO3
minus reab-sorption produce alkalosis27
paeDiatRiCS anD CHilD HealtH 184 17
Metabolic alkalosis may also occur with excessive loss of gas-tric contents eg protracted vomiting or inadequate replacement of nasogastric aspirates (see Table 1)
Interpreting blood gases
Blood gas measurements can provide important diagnostic and prognostic information and a systematic approach to blood gas analysis is described in Table 2 The clinical management of infants with abnormal gases requires a good understanding of acidndashbase physiology and tissue oxygenation and an apprecia-tion of factors which may affect the reliability of samples
Arterial blood sampling is the gold standard however indwelling arterial catheters and arterial stab samples are usually restricted to infants who are critically ill or those who require sig-nificant ongoing intervention Gases are most frequently measured in capillary or venous samples which correlate well with arterial samples for PaCO2 pH and base excess in babies and children receiving intensive care These correlations however are not valid in infants with peripheral vasoconstriction and hypotension2324
Non-invasive monitoring techniques may enable us to reduce the frequency of blood gas sampling Transcutaneous monitoring
5 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
A systematic approach to blood gas analysis
1 Collect the relevant information
bull type of gas ndash capillary or arterial
bull Current respiratory support ndash document level
bull transcutaneous Co2 and Sao2 levels
bull Clarify no significant clinical events before sampling
2 pH accept a range between 730 and 745 in newborn
babies this is lower than in older children is there an
alkalosis (pH gt 745) or an acidosis (lt 730)
3 Co2 aim for a range between 45 and 65 kpa a paCo2 level
more than 65 kpa suggests inadequate alveolar ventilation
while less than 45 kpa suggests hyperventilation Correlate
values with non-invasive measures
4 o2 Can only be assessed from arterial gases aim for pao2
between 60 and 80 kpa Correlate results with pulse
oximetry levels
5 HCo3 and base excess normal HCo3 level is between 20 and
24 mmollitre and bases excess +3 to minus3
6 anion gap look at the anion gap and lactate to help identify
the cause of an acidosis normal lactate levels should be less
than 2 mmollitre
7 Respiratory or metabolic compensation look at the pH and
assess whether it is appropriate for the Co2 level or is there
evidence of compensation
8 interpret use both the clinical history and blood gas
findings to help you identify the primary problem aim your
management at treating the underlying cause
9 Reassess if clinical management changes have been made
repeat the blood gas after an appropriate time interval to
ensure improvement
Table 2
provides a highly accurate and reliable method for measuring PaCO2 through the skin it can however be technically difficult may cause tissue damage and is of limited reliability when peripheral perfusion is reduced25 Continuous end-tidal CO2 measurements correlate well with arterial CO2 values in patients with normal ventilation and perfusion however in babies with lung disease alveolar collapse small tidal volumes and rapid respiratory rates can make these measurements unreliable26 Despite its limitations transcutaneous monitoring provides the best method for CO2 trend monitoring in the neonatal intensive care unit (NICU)25
Oxygen saturation levels can be continuously measured non-invasively using pulse oximetry While oximetry is easy to perform and accurate on occasion SaO2 levels obtained may be unreliable when tissue perfusion is poor or with movement artefact SaO2 monitoring is highly sensitive at detecting hypoxia but is limited in detecting hyperoxia as at levels more than 90 small changes in SaO2 may result in unacceptably large increases in PaO227 It is therefore essential that SaO2 alarm limits are set for all neonates receiving respiratory support to detect hypoxia and prevent hyperoxia1627
Continuous non-invasive monitoring provides invaluable information when managing complex infants in the NICU but it does not replace the need for regular blood gas analysis
paeDiatRiCS anD CHilD HealtH 184 17
ReFeRenCeS
1 Kellum Ja Determinants of blood pH in health and disease
Crit Care 2000 4 6ndash14
2 Quigley R Baum m neonatal acid base balance and disturbances
Semin Perinatol 2004 28 97ndash102
3 Brouillette Rt Waxman DH evaluation of the newbornrsquos blood gas
status Clin Chem 1997 43 215ndash221
4 Chan JC acid-base disorders and the kidney Adv Pediatr 1983 30
401ndash471
5 Siggaard-andersen o the pH-log pCo2 blood acidndashbase nomogram
revised Scand J Lab Invest 1962 14 598ndash604
6 Saetta m mortola Jp interaction of hypoxic and hypercapnic stimuli
on breathing pattern in the newborn rat J Appl Physiol 1987 62
506ndash512
7 Baum m Quigley R postnatal renal development in Seldin DW
giebisch g eds the kidney physiology and pathophysiology new
york lippincott Williams and Wilkins 2000 p 703ndash726
8 ortiz la Quan a Weinberg a et al effect of prenatal
dexamethasone on rat renal development Kidney Int 2001 59
1663ndash1669
9 gabow pa Kaehny WD Fennessey pV goodman Si gross pa
Schrier RW Diagnostic importance of an increased serum anion gap
N Engl J Med 1980 303 854ndash858
10 lorenz Jm Kleinman li markarian K oliver m Fernandez J Serum
anion gap in the differential diagnosis of metabolic acidosis in
critically ill newborns J Pediatr 1999 135 751ndash755
11 Deshpande Sa platt mp association between blood lactate and
acid-base status and mortality in ventilated babies Arch Dis Child
1997 76 F15ndash20
12 Stewart pa modern quantitative acid-base chemistry Can J Physiol
Pharmacol 1983 61 1444ndash1461
13 Dakshinamurti S pathophysiologic mechanisms of persistent
pulmonary hypertension of the newborn Pediatr Pulmonol 2005
39 492ndash503
14 mourani pm ivy DD gao D abman SH pulmonary vascular
effects of inhaled nitric oxide and oxygen tension in
bronchopulmonary dysplasia Am J Respir Crit Care Med 2004
170 1006ndash1013
15 Deulofeut R Critz a adams-Chapman i Sola a avoiding hyperoxia
in infants le 1250 g is associated with improved short- and long-
term outcomes J Perinatol 2006 26 700ndash705
16 Chow lC Wright KW Sola a Can changes in clinical practice
decrease the incidence of severe retinopathy of prematurity in very
low birth weight infants Pediatrics 2003 111 339ndash345
17 Boylan gB young K panerai RB Rennie Jm evans DH Dynamic
cerebral autoregulation in sick newborn infants Pediatr Res 2000
48 12ndash17
18 Kaiser JR gauss CH pont mm Williams DK Hypercapnia during
the first 3 days of life is associated with severe intraventricular
hemorrhage in very low birth weight infants J Perinatol 2006 26
279ndash285
19 Fabres J Carlo Wa phillips V Howard g ambalavanan n Both
extremes of arterial carbon dioxide pressure and the magnitude of
fluctuations in arterial carbon dioxide pressure are associated with
severe intraventricular hemorrhage in preterm infants Pediatrics
2007 119 299ndash305
20 thome uH Carroll W Wu tJ et al outcome of extremely preterm
infants randomized at birth to different paCo2 targets during the
first seven days of life Biol Neonate 2006 90 218ndash225
6 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
21 Carlo Wa Stark aR Wright ll et al minimal ventilation to prevent
bronchopulmonary dysplasia in extremely-low-birth-weight infants
J Pediatr 2002 141 370ndash374
22 okumura a Hayakawa F Kato t et al Hypocarbia in preterm
infants with periventricular leukomalacia the relation between
hypocarbia and mechanical ventilation Pediatrics 2001 107
469ndash475
23 peters o Ryan S matthew l Cheng K lunn J Randomised
controlled trial of acetate in preterm neonates receiving parenteral
nutrition Arch Dis Child 1997 77 F12ndash15
24 yildizda D yapiciolu H yilmaz Hl Sertdemir y Correlation of
simultaneously obtained capillary venous and arterial blood gases
of patients in a paediatric intensive care unit Arch Dis Child 2004
89 176ndash180
25 aliwalas ll noble l nesbitt K et al agreement of carbon
dioxide levels measured by arterial transcutaneous and end tidal
methods in preterm infants 28 weeks gestation J Perinatol 2005
25 26ndash29
26 Hagerty JJ Kleinman me Zurakowski D et al accuracy of a new
low-flow sidestream capnography technology in newborns a pilot
study J Perinatol 2002 22 219ndash225
paeDiatRiCS anD CHilD HealtH 184 17
27 poets CF Wilken m Seidenberg J Southall Dp von der Hardt H
Reliability of a pulse oximeter in the detection of hyperoxemia
J Pediatr 1993 122 87ndash90
Practice points
bull a stable extracellular pH is important for optimal cellular
functioning
bull abnormalities in acidndashbase balance are regulated by buffer
systems and the respiratory and renal tract
bull maintaining a stable pH is challenging for newborn babies
due to their high rates of acid production and immature
regulatory mechanisms
bull arterial or capillary blood gases provide an effective way to
monitor acidndashbase balance in newborns
bull Blood gases should be analysed in a structured manner
assessing pH and then respiratory and metabolic components
bull the treatment of acidndashbase abnormalities should be directed
at the underlying problem not merely at correcting pH
7 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Recognition and management of neonatal seizuresmalcolm levene
AbstractSeizures are the most common major manifestation of central nervous
system dysfunction in the newborn there are many causes but perina-
tal asphyxia and haemorrhagicinfarction lesions account for about 75
there is now considerable evidence that frequent but short seizures in
the neonate affect subsequent neurodevelopmental outcome Studies
using eeg or modified continuous tracing of eeg activity (aeeg or CFm)
have shown that there is often electroconvulsive dissociation this re-
fers to poor correlation between electrical seizures and clinical seizures
Commonly used anticonvulsants appear to increase electroconvulsive
dissociation effective management of neonatal seizures has proved very
disappointing and less than 50 of seizures are abolished by first-line
anticonvulsant medication (phenobarbitone or phenytoin) Drugs such
as midazolam and lidocaine may further reduce seizures but require
more evaluation the challenge is to assess new and more effective anti-
convulsants which are themselves associated with little neurotoxicity
Keywords antiepileptic drugs eeg neonatal seizures neurodegeneration
Convulsions are the most common major neurological sign seen in newborn infants and their incidence estimated from large population studies is 26 per 1000 live births1 Premature infants are over four times more likely to have convulsions than full-term infants12 Neonatal status epilepticus (continuous seizure activity lasting 30 min or more) diagnosed clinically is rare and accounts for only 5 of infants with seizures1 although this is now recognized more frequently as the result of continuous EEG monitoring3
Neonatal convulsions are described as presenting in a num-ber of different ways and various seizure types can be seen in the same baby over a number of hours The frequencies of the various patterns of seizure activity are given in Table 1 In very premature babies and to a lesser extent in term infants minor movement abnormalities may be difficult to identify as subtle seizures These include lip smacking tongue thrusting mouth-ing pedalling type movements of the lower limbs or swimming movements of the arms Apnoea can be a common manifesta-tion of subtle seizures The signs can be protean and vary from baby to baby or even in the same baby Virtually any stereotypic
Malcolm Levene MD FMedSc FRCPCH FRCH is Professor and Head of
Department of Paediatrics and Child Health at University of Leeds Leeds
and Honorary Neonatologist at Leeds General Infirmary Leeds UK
paeDiatRiCS anD CHilD HealtH 184 178
movement may be a manifestation of a seizure disorder in the newborn
Aetiology
The more carefully the fitting baby is investigated the more likely it is that a cause for the seizures will be found A number of recent papers have described the aetiology of neonatal con-vulsions after extensive investigations14 Tekgul et al4 recently studied a consecutive group of full-term infants with evidence of neonatal convulsions (recognized both clinically and on EEG) and reported their outcome Table 2 summarizes these data as well as risk of moderate or severe disability for each causative factor Perinatal asphyxia is the commonest cause for convul-sions in term infants with haemorrhagic or ischaemic lesions also being common
Overall the prognosis for the group of term babies with con-vulsions was good 72 had a favourable outcome Where asphyxia (hypoxicndashischaemic insult) is the cause of neonatal convulsions the outcome is poor in 50 The prognosis for neonatal convulsions when they were due to arterial or cere-brovenous infarction or intracranial haemorrhage was generally good Individually inborn errors are a very rare cause of neo-natal convulsions but in view of the treatable nature of some of these it is essential that these be considered and investigated appropriately5
Patterns of seizure activity in the newborn
Movement pattern Frequency ()
Clonic 50
tonic 20
Subtle 10ndash35 depending on maturity
myoclonic 5
Table 1
Cause incidence and outcome of neonatal convulsions in term infants14
Aetiological factor Incidence () Poor outcome ()
asphyxia 38ndash40 50
Cerebral arteriovenous
infarction
20 0
intracranial haemorrhage 12ndash20 13
Congenital cerebral anomaly 5ndash10 100
Hypoglycaemiahypocalcaemia 3ndash19
infection 3ndash20
inborn error of metabolism 1
unknown cause 10ndash13 0
Refers to moderate and severe neurodevelopmental abnormalitynumbers too small to make meaningful predictions
Table 2
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Controversies in the clinical management of neonatal seizures
In recent years we have learnt much more about the neurobi-ology of seizures and their effect on the developing brain The neonatal brain is in a neurophysiologically hyperexcitable state compared to the more mature brain and therefore is more prone to seizure activity This is due largely to a relative excess of GABA neuroreceptors GABA receptors are usually inhibitory but in the immature brain they have a paradoxically excitatory effect This changes at about term in primates and with progressive develop-ment they adopt a neuroinhibitory role6
The propensity to seizures in the neonatal brain makes resolv-ing the balance of risks between continuing seizure activity on the one hand against potentially adverse effects of therapy on the other a very important equation Added to this is the problem of accurately diagnosing neonatal seizures and whether commonly used anticonvulsants are successful in controlling them
These conundrums can be posed as a series of challenging questions which are discussed below
Do neonatal convulsions cause brain injuryConvulsions are a sign of neurological compromise and may indi-cate significant underlying structural brain damage or biochemi-cal disturbance which may cause further brain damage in its own right There has been considerable debate about the scale of the disability that convulsions cause the immature brain over and above that due to the underlying cause Most of our knowledge comes from studies in rodents and these have provided some tentative answers to this question
Seizures in the mature brain lead to neuronal necrosis but studies in very young rat pups whose brain development is somewhat similar to full-term infants have shown that a series of five brief seizures on five successive days does not cause struc-tural neuronal damage but does produce morphological changes in hippocampal neurones and worryingly deficits in the rat learning and visual spatial memory function in adolescent and adult life7 A single prolonged neonatal convulsion in similarly immature rats does not produce any functional effects8 Others have shown that following priming of the neonatal rat brain by short seizures as described above a further insult comprising induction of status epilepticus in the same rats at an older age causes neuronal necrosis9 This has been referred to as the lsquotwo hit hypothesisrsquo10
A more specific question is does seizure activity in an already significantly compromised brain cause additional neuropathol-ogy Wirrell et al11 studied a series of immature rat pups with the induction of an hypoxicndashischaemic (asphyxial) insult fol-lowed by either chemically-induced fits or a control sham pro-cedure In the more severely asphyxiated animals the degree of brain damage was increased significantly in those that had the additional burden of induced seizures
In summary these studies show that the immature brain is more resistant to short frequent post-seizure damage than the mature brain but despite resulting in no loss of neuronal numbers the function of the brain is permanently affected in later life In the asphyxiated brain seizures appear to have an additional adverse effect on brain damage Furthermore the immature brain that has been lsquoprimedrsquo by early seizures is more
paeDiatRiCS anD CHilD HealtH 184 179
vulnerable to status epilepticus later in life It would appear from these data that frequent seizures in the human infant should be stopped and this begs the question as to whether currently used anticonvulsants effectively control neonatal seizures
Can we rely on clinical versus EEG diagnosis of neonatal convulsionsTraditionally the diagnosis of neonatal convulsions has been made by observation and description of the frequency of abnor-mal movements EEG has been technically difficult in the hostile electrical activity of a neonatal intensive care environment and considerable expertise is required for analysis of the trace It is usually not practical to undertake traditional EEG recordings at the time the baby shows abnormal movements More recently various technological developments have allowed more direct investigation of neuronal electrical activity by either video-EEG or compressed recording of the amplitude integrated EEG (aEEG or CFM)
Rennie et al3 at Kingrsquos College Hospital London have under-taken extensive evaluation of video-EEG and have found that this technique detects many convulsions not recognized by a single channel aEEG or CFM trace Of 19 infants with evidence of convulsions on EEG only four were recognized on CFM but this may have been due to the observersrsquo lack of experi-ence with this technique In other centres that have developed appropriate expertise aEEG or CFM has proved more sensitive to the detection of seizures Video-EEG studies have also shown that many movements interpreted by experienced clinicians to be seizures are not associated with abnormal cortical activity Conversely many electrical seizures are not associated with abnormal movements This is referred to as electroconvulsive dissociation
In summary clinical observation alone to detect the fitting baby is unreliable in that it may either over-detect seizure activ-ity which is not present on EEG or under-detect clinical seizures in infants with EEG-proven convulsions The decision as to which babies to treat with antiepileptic drugs therefore becomes somewhat arbitrary
Do anticonvulsants stop neonatal seizuresAlthough neonatal seizures are common there are few random-ized controlled trials assessing the benefits of antiepileptic drugs (AEDs) in the treatment of this condition Phenobarbitone is the most widely used first-line AED and in an Australasian study 95 of neonatologists and paediatric neurologists used this drug as first-line management12 The most commonly used loading dosage is 20 mgkg but regimens of up to 40 mgkg have been recommended (Table 3)13 Four trials have evaluated the effect of phenobarbitone in abolishing neonatal seizures Two of these studies used EEG to monitor response to the drug1415 and one compared phenobarbitone with phenytoin15 In the latter study seizures were completely controlled in only 43 of babies and in the group where phenytoin was the first drug used com-plete seizure control was achieved in 45 This study switched babies from their first AED to the other if complete control was not obtained on EEG monitoring after exposure to first-line therapy In babies who had been given phenobarbitone as first-line therapy seizure control was only achieved in 57 after phenytoin was added In those given phenytoin first complete
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Dosage regimens for first- second- and third-line anticonvulsants in the neonatal period
Loading dose Second loading dose if first
unsuccessfulMaintenance dose
phenobarbitone 20 mgkg by slow iv injection 10 mgkg iv 25ndash5 mgkg od
phenytoin 20 mgkg iv over 20 min not recommended
midazolam 150ndash200 μgkg iv infusion 1 μgkgmin iv infusion increasing to 5 μgkgmin
until favourable response
lidocaine 2 mgkg iv over 10 min 6 mgkgh for 6 h iv then 4 mgkgh for 12 h then
2 mgkgh for 12 h
lorazepam 005ndash01 mgkg by slow iv injection
Diazepam 03ndash04 mgkg iv over 3ndash5 min
lidocaine should not be used if the infant has previously been treated with phenytoin
Table 3
seizure control was achieved with the adding of phenobarbitone in 62
Boylan et al14 assessed the efficacy of phenobarbitone (20ndash40 mgkg iv over 20 min) in 14 babies monitored by video-EEG in only four was there complete abolition of seizures and in the other 10 electroconvulsive seizure activity increased whereas clinical evidence of seizures reduced This has been termed elec-troclinical dissociation and anticonvulsant drug use in the new-born appears to increase this feature They also showed that the babies least likely to respond to the first-line AED are those with the most abnormal background EEG
Two studies have evaluated the use of phenobarbitone in babies who had sustained significant asphyxial insult at birth Hall et al13 compared high-dose phenobarbitone (mean 39 mgkg) versus standard dose (27 mgkg) and reported fewer convul-sions and a significant reduction of severe disability or death in the high dose group (RR 030 CI 010ndash093) A recent study from India16 of babies with hypoxicndashischaemic encephalopathy ran-domized 25 babies to phenobarbitone (20 mgkg loading dose) and compared them with 20 control babies Only 2 of 25 (4) in the phenobarbitone group developed convulsions compared with 8 of 20 (40) in the control group (p = 001) Because of the specific enrolment criteria (asphyxial insult) neither of these studies is strictly comparable to the studies by Painter et al15 and Boylan et al14 whose intention was to assess the efficacy of first-line anticonvulsant therapy on convulsions of any cause diagnosed either clinically or by EEG
Other anticonvulsants used as second- and third-line drugs have been subject to few studies in the newborn Midazolam is administered as a bolus followed by continuous infusion A recent study17 has shown that in 10 of 13 neonates given intravenous midazolam for status epilepticus control of electri-cal seizures was achieved within the first hour of treatment having been previously shown to be refractory to phenobarbi-tone treatment Some of these babies required a second bolus infusion of midazolam to obtain control of all electrographic seizures
In some parts of Europe lidocaine is used as a third-line anti-convulsant Malingre et al18 evaluated 20 infants refractory to
paeDiatRiCS anD CHilD HealtH 184 180
both phenobarbitone and midazolam and who were then given lidocaine by continuous infusion Lidocaine was effective in abolishing electroconvulsive seizures diagnosed by aEEG in 76 of the treatment courses studied No babies developed cardiac arrhythmias a previously reported complication of lidocaine in older patients As a result of pharmacokinetic studies the dosage regimen has been modified (see Table 3)
In summary phenobarbitone is effective in seizure control in less than 50 of babies and even when combined with phe-nytoin the efficacy of these drugs together remains poor More worrying is the observation that phenobarbitone tends to reduce clinically evident seizures thereby giving the clinician a false sense of security whilst having little or no effect on the num-bers of electroconvulsive disorders This has been summarized appropriately as lsquoafter all these years we still love what doesnrsquot workrsquo19 Both midazolam and lidocaine infusions appear to be effective in abolishing severe seizures in some infants resistant to phenobarbitone Lidocaine should not be given to babies previ-ously exposed to phenytoin for fear of a synergistic adverse effect on cardiac rhythm
Do antiepileptic drugs cause brain damageA riskndashbenefit analysis is needed to evaluate the efficacy of anticonvulsants in stopping neonatal seizures which is poor with standard anticonvulsants as discussed above against the risk of administering the anticonvulsant drugs themselves Phenobarbitone has been reported to have adverse effects on the developing brain including inhibition of brain growth20 neuronal toxicity21 and adverse behavioural and cognitive effects into adult life when administered to young animals22 Phenytoin shows unpredictable plasma levels and potential cardiotoxicity
Recent studies have shown an effect of AED exposure on the developing brain by causing neurodegeneration23 Phenytoin administration to immature rat pups at doses which produce serum levels similar to those achieved in human neonates was associated with widespread neuronal death as a result of apop-tosis (programmed cell death) Phenobarbitone had a similar effect when a dosage regimen similar to 40 mgkg was used and
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
this effect was maximal in the more immature brain Diazepam and clonazepam also resulted in a similar effect Midazolam and lidocaine were not tested in this study The combination of phenobarbitone or phenytoin with diazepam had a particularly profound effect on neurodegeneration
In summary recent data suggest that the commonly used AEDs for neonatal convulsions may in themselves cause neuro-degeneration due to apoptosis with lasting effects on develop-ment Many babies with neonatal convulsions are treated with at least two AEDs and this may produce more severe adverse effects than the seizures themselves
Practical management of neonatal seizures
Assimilation of these data and formulation of a rational policy is difficult when faced with a fitting neonate on an intensive care unit and pressure on the medical staff to lsquodo somethingrsquo but it is important to accept that sometimes doing nothing is preferable to using potentially dangerous drugs in a situation which does not warrant such intervention Many babies who have normal interseizure neurological clinical findings and whose seizures are relatively brief and infrequent probably do not need anticon-vulsant medication A normal or near-normal background EEG trace should reassure the clinician that anticonvulsants can be withheld
Some causes of neonatal convulsions are treatable such as meningitis hypoglycaemia hypocalcaemia and inborn errors of metabolism and each baby should be rapidly and carefully investigated for cause of the convulsions
In some babies clinical assessment of seizures is difficult ie when the baby is very sick small or paralyzed Sometimes it may be difficult to assess the significance of certain movement pat-terns Under these circumstances an EEG may prove to be very helpful In many units EEG is not available out of hours and a simple aEEG or CFM is strongly advised Modern instruments are very simple to apply and prolonged or frequent seizures should be identified with only moderate training The printout can be faxed to a more senior doctor if there is doubt as to what is shown on the trace
The balance of knowledge now is that frequent seizures cause additional damage to the developing brain and that treatment to abolish the seizures is warranted Unfortunately there is little evidence that the majority of seizures can be effectively termi-nated by current standard therapy Furthermore it appears that the more abnormal the background EEG the more difficult it is to control the seizures Nevertheless a written protocol for the management of neonatal convulsions is required on each unit Phenobarbitone and phenytoin remain the mainstay of treat-ment although their effectiveness is disappointing There is little to suggest that midazolam is more effective than lidocaine as third-line therapy but lidocaine is precluded if phenytoin has been previously used
In view of the anxiety as to the neurodegenerative effects on the immature brain of most anticonvulsants used in the neonatal period (particularly when multiple drugs are used) it is prefer-able to use only one drug to maximum dosage before introduc-ing a second In addition the duration of anticonvulsants should be minimized and the drugs stopped at the earliest opportu-nity It is my practice to stop anticonvulsants prior to discharge
paeDiatRiCS anD CHilD HealtH 184 18
from hospital if the baby is neurologically normal on clinical examination
REFEREnCES
1 Ronen gm penney S andrews W the epidemiology of clinical
neonatal seizures in newfoundland a population-based study
J Pediatr 1999 134 71ndash75
2 lanska mJ lanska DJ Baumann RJ et al a population-based study
of neonatal seizures in Fayette County Kentucky Neurology 1995
45 724ndash732
3 Rennie Jm Chorley g Boylan gB et al non-expert use of the
cerebral function monitor for neonatal seizure detection Arch Dis
Child Fetal Neonatal Ed 2004 89 F37ndashF40
4 tekgul H gauvreau K Soul J et al the current etoliologic profile
and neurodevelopmental outcome of seizures in term newborn
infants Pediatrics 2006 117 1270ndash1280
5 Surtees R Wolf n treatable neonatal epilepsy Arch Dis Child 2007
92 659ndash661
6 Ben-ari y Holmes gl effects of seizures on developmental
processes in the immature brain Lancet Neurol 2006 5 1055ndash
1063
7 Holmes gl gairsa Jl Chevassus-au-louis n et al Consequences of
neonatal seizures in the rat morphological and behavioral effects
Ann Neurol 1998 44 845ndash857
8 Stafstrom Ce Chronopoulos a thurber S et al age-dependent
cognitive and behavioural deficits following kainic-acid inducing
seizures Epilepsia 1993 34 420ndash432
9 Schmid R tandon p Stafstrom Ce et al effects of neonatal seizures
on subsequent seizure-induced brain injury Neurology 1999 53
1754ndash1761
10 Hoffmann aF Zhao Q Holmes gl Cognitive impairment following
status epilepticus and recurrent seizures during early development
support for the ldquotwo-hit hypothesisrdquo Epilepsy Behav 2004 5
873ndash877
11 Wirrell eC armstrong ea osman lD et al prolonged seizures
exacerbate perinatal hypoxic-ischemic brain damage Pediatr Res
2001 50 445ndash454
12 Carmo KB Barr p Drug treatment of neonatal seizures by
neonatologists and paediatric neurologists J Paediatr Child Health
2005 41 313ndash316
13 Hall Rt Hall FK Daily DK High-dose phenobarbital therapy in term
newborn infants with severe perinatal asphyxia a randomized
prospective study with three-year follow-up J Pediatr 1998 132
345ndash348
14 Boylan gB Rennie Jm pressler Rm et al phenobarbitone neonatal
seizures and video-eeg Arch Dis Child Fetal Neonatal Ed 2002 86
F165ndash170
15 painter mJ Scher mS Stein aD et al phenobarbital compared with
phenytoin for the treatment of neonatal seizures N Engl J Med
1999 341 485ndash489
16 Singh D Kumar p narang a a randomized controlled trial of
phenobarbital in neonates with hypoxic ischemic encephalopathy
J Matern Fetal Neonatal Med 2005 18 391ndash395
17 Castro Conde JR Borges H Domenech martinez e et al midazolam
in neonatal seizures with no response to phenobarbital Neurology
2005 64 876ndash879
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
18 malingre mm Van Rooij lgm Rademaker Cma et al Development
of an optimal lidocaine infusion strategy for neonatal seizures Eur
J Pediatr 2006 165 598ndash604
19 Sankar R painter mJ neonatal seizures after all these years we still
love what doesnrsquot work Neurology 2005 64 776ndash777
20 Diaz J Schain J Bailey Bg phenobarbital-induced brain growth
retardation in artificially reared rat pups Biol Neonate 1977 32 77ndash82
21 mattson RH phenobarbital toxicity in levy RH Dreifuss Fe
mattson RH et al eds antiepipeptic Drugs 3rd edn new york
Raven 1985 p 341ndash355
22 mikati ma Holmes gl Chronopoulos a et al phenobarbital
modifies seizure-related brain injury in the developing brain Ann
Neurol 1994 36 425ndash453
23 Bittigau p Sifringer m genz K et al antiepileptic drugs and
apoptotic neurodegeneration in the developing brain Proc Natl
Acad Sci U S A 2002 99 15089ndash15094
paeDiatRiCS anD CHilD HealtH 184 182
Practice points
bull the clinician needs to be aware that almost any repetitive
stereotype movement pattern can be a manifestation of
neonatal seizures
bull eeg is important in defining neonatal seizures
bull Frequent short-lived seizures have been shown to cause long-
term neurodevelopmental problems
bull Conventional anticonvulsant medication is ineffective in
abolishing neonatal seizures in greater than 50 of cases
bull there is evidence that exposure of the neonatal brain to
multiple anticonvulsants causes neuronal death
bull Future research is needed to evaluate more effective
anticonvulsants for treating this condition
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
Emotional support for families of sick neonatesMarina nicolaou
cristine Glazebrook
AbstractParents of sick neonates experience high levels of stress anxiety and
depression Most interventions with families of sick infants have focused
on fostering the motherndashinfant relationship through the provision of
information about infant developmental needs or through increased
motherndashinfant contact Many of these studies have reported improved
maternal well-being though there are some concerns about the scope
and practicality of large-scale interventions The few studies to have
prioritized emotional support for parents of sick neonates have pro-
duced encouraging results even interventions requiring relatively few re-
sources such as telephone support parent-to-parent support and group
support have been associated with reduced psychological morbidity for
parents The needs of parents can change throughout their infantrsquos hos-
pitalization and not all want or benefit from the provision of additional
support Thus neonatal intensive care units should aim to provide a
varied flexible and sustainable programme of support options Further
research should focus on the needs of fathers
Keywords mental health neonatal intensive care parents
The admission of an infant to neonatal care is acknowledged to be a source of considerable distress for families This review aims to explore evidence for the psychological impact on families of having an infant in neonatal intensive care and to identify evi-dence for the effectiveness of interventions to promote parental well-being It will conclude with recommendations for strategies to support parents of vulnerable infants and suggestions for fur-ther research
Psychological impact of neonatal care for parents
The majority of research examining the effect on parents of having a sick neonate has focused on families of premature or low birthweight infants Such research has found that parents with a sick neonate exhibit high levels of stress compared to normative samples and to parents of healthy full-term infants1 Singer et al2 examined the stress experienced by mothers of high-risk very low birthweight (VLBW) low-risk VLBW and term
Marina Nicolaou MPhil is a Teaching Assistant at the School of
Community Health Sciences University of Nottingham Nottingham UK
Cristine Glazebrook PhD is a Professor of Health Psychology at the School
of Community Health Sciences University of Nottingham Nottingham UK
PaeDiaTrics anD cHilD HealTH 184 196
infants Several self-report measures were used including the Brief Symptom Inventory the Parenting Stress Index (PSI) the Impact on Family Scale and the Family Inventory of Life Events and Changes (FILE) Mothers of VLBW infants had more psycho-logical distress at 1 month compared to mothers of term infants Mothers of high-risk VLBW infants also reported high psycho-logical distress at 2 years and high levels of parenting stress at 3 years Mothers have also been found to have higher stress levels compared to fathers Shaw et al3 examined the prevalence of acute stress disorder (ASD) in 40 parents whose infants were in the neonatal intensive care unit (NICU) Nearly half of the moth-ers (44) met the criteria for ASD although none of the fathers did Furthermore the severity of the symptoms (measured by the number of concurrent symptoms) was greater for the moth-ers than for the fathers3 The reasons behind this difference have been widely speculated with some believing that it is due to the mothersrsquo greater psychological involvement with the infant as evidenced by their general greater vulnerability to postpartum psychological disorder It could also reflect gender differences in coping style
Having an infant who requires intensive medical care repre-sents a significant emotional burden for families Not only is there extreme anxiety surrounding the infantrsquos health and distress for the childrsquos suffering there is also the unfamiliar and intimidating environment of the NICU to adjust to Hopper in her review of the literature identified sources of stress for parents of sick neo-nates as falling into three areas4 Situational factors included the severity of the infantrsquos illness and how parents adapted to the life crisis of having a sick infant Personal factors involved parental emotions about their roles and the instrumental and informa-tional support which were available to them The third area was classified as environmental sources of stress and included the environment of the NICU and the relationship between parents and members of staff This relationship has been examined by several studies in the nursing literature nurses are seen as ide-ally placed to provide the necessary support and information to parents with sick neonates However whilst some studies have shown that supportive and helpful hospital staff can have a posi-tive effect on parents other studies have highlighted the prob-lems and difficulties which can manifest It has been shown that parents and nurses often have very different ideas about issues eg the necessary skills and competencies needed in an NICU or the characteristics that make a lsquogood motherrsquo
Research has shown that there may be a relationship between high levels of parental stress and an increased likelihood of depression5 Postpartum depression is a psychiatric illness which appears in 10ndash15 of postpartum women Its reported preva-lence rates however have ranged from less than 10 up to 306 depending on the instruments used the population exam-ined and the timing of the research Several factors have been found to be associated with postpartum depression including poor social support and infant-related stressors6 Evidence indi-cates that postnatal depression may be underreported and this is of concern since the mental and psychological health of the mother can affect her relationship with her infant and thus the infantrsquos cognitive and emotional development5 Depressed moth-ers appear to look touch and talk to their infants less frequently and also appear to show fewer positive and more negative faces7 The vocalizations of mothers suffering with depression have also
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
been found to be less effective at promoting cognitive growth and learning in infants8
If researchers are interested in finding ways of providing sup-port for families of sick neonates then they must listen to what such families perceive their needs to be in order to avoid increas-ing anxiety and distress Furthermore the provision of appropri-ate support be it emotional informational or social will enhance parental coping abilities increase self-esteem and reduce anxiety It should be noted though that the research conducted around these issues has often taken lsquosupport needsrsquo as being synony-mous with lsquoinformation needsrsquo Such studies have examined the type the amount and quality of information that parents receive and perceive themselves as needing but have not explored in equal depth the perceived emotional support needs of families who have a sick infant In addition the needs of parents may change throughout their infantrsquos illness Ward examined the per-ceived needs of 52 parents of infants in an NICU9 Parents rated the needs of their hospitalized infant as most important along with the need to be reassured Interestingly they ranked their support needs as least important This research was conducted during the first week of the infantsrsquo hospitalization however which would explain the preoccupation of the parents with the infantrsquos health These results demonstrate that if researchers want to find ways of providing emotional support to parents of sick neonates they must be prepared not only to listen to parents but also to be flexible enough to satisfy the parentsrsquo changing needs and expectations
Interventions aimed at supporting parents
Most interventions that been evaluated in controlled studies have focused on supporting the motherndashinfant relationship and provid-ing information on infant development Many of these interven-tions have included the aim of improving the parental emotional state and thus psychological outcomes such as stress or anxi-ety have been assessed However few studies appear to include fathers This means that strategies implemented to provide emo-tional support to families of sick neonates are often derived from interventions tailored for mothers even though fathers may have different emotional needs
A wide range of interventions with mothers and infants has been evaluated in the NICU Increasing motherndashinfant contact through kangaroo care has been found to reduce maternal anxiety1011 and educational programmes delivered to fami-lies in the NICU have also been associated with reduced emo-tional difficulties in parents12ndash14 Kaaresen and colleagues implemented an intervention which consisted of eight sessions before discharge and four home visits all by trained nurses The sample included 71 premature infants in the intervention group 69 premature infants in the control group and 74 infants in the full-term control group The randomized controlled trial found that the intervention reduced parenting stress in both mothers and fathers of premature infants compared to controls to a level equivalent to parents in the term control group13 At 6 months corrected age mothers of preterm infants who had not received the intervention had total PSI scores which were 17 points higher than the mothers of infants born at term (an effect size of 057) A similar study evaluated the efficacy of an educationalndashbehavioural programmendashCreating Opportunities for
PaeDiaTrics anD cHilD HealTH 184 19
Parent Empowerment (COPE) ndash through a randomized controlled trial with 260 families of premature infants14 COPE was a four-phase educationalndashbehavioural programme which began as early as 2ndash4 d after mothers had given birth and continued until 1 week after discharge from the NICU The programme consisted of audiotaped and written infant behaviour information along with photographs which focused on common behaviours and characteristics of premature infants It also included various par-ent activities in the form of a four-phase workbook which aimed to assist mothers in the implementation of the experimental infor-mation COPE was found significantly to reduce maternal stress in the NICU as well as maternal anxiety and depressive symptoms after hospitalization In contrast a cluster randomized trial of a parenting intervention delivered to mothers of very premature infants from soon after birth showed no benefits for parenting stress1 The authors hypothesized that the intervention had not been of sufficient intensity particularly in the weeks surrounding discharge Neonatal care presents a significant barrier to parent-ing in the early weeks following a very preterm birth and so inter-ventions which focus on the developmental needs of infants and the parentndashchild relationship should particularly aim to support parents as they take on the parenting role There was also concern that the intervention had failed to reach those most at risk
Since large-scale projects can be costly to implement and may often fail to reach the families in most need it may be wiser to focus on intervention programmes which are more practical and easier to implement within a neonatal care setting Research has shown that even interventions which are based on one-off meet-ings with parents of sick neonates can be effective Jotzo and Poets examined the effect of an intervention programme aimed at reducing the severity of traumatic responses as a result of giv-ing birth prematurely15 Their programme consisted of a one-off intervention meeting along with additional psychological help throughout the hospitalization of the infant The meeting cov-ered a variety of issues including a reconstruction of the events shortly before and after the infantrsquos birth relaxation techniques discussion of coping strategies available resources and social support and support during emotional outbursts The measures used included the Impact of Event Scale (IES) and the Peritrau-matic Dissociative Experience Questionnaire At discharge the mothers who received the intervention were found to have a significantly lower traumatic impact as a result of premature birth Furthermore fewer mothers in the intervention group showed symptoms of clinically significant psychological trauma at discharge compared to mothers in the control group (36 vs 76)15 The lsquoParents Circle Programrsquo is another intervention with a similar structure16 This consisted of a 90 min session for parents with the aim of enhancing the developing relationship between parents and infants and to offer parents support A total of 104 parents (59 mothers and 45 fathers) and 44 members of hospital staff were asked to evaluate the programme and their results were analysed using content analysis Families reported gaining perspective on their situation feeling supported becom-ing aware of cues and optimizing interactions and becoming aware of available resources Parents and staff alike felt that participating in the intervention helped parents overcome the difficulties associated with the early time of their infantrsquos hos-pitalization Additional studies have also found positive results with fairly minimal interventions including discussion groups
7 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
in the NICU music during kangaroo care and pairing mothers of sick neonates with trained mothers who had been through similar experiences
Parent support programmes
Parent support programmes (PSPs) which are based in NICUs can provide parents with the opportunity to talk to parents who have been in similar situations and also to discuss their emo-tions with professionals who can help them cope with their situa-tion111718 The parent-to-parent support programme for mothers of preterm infants evaluated by Preyde and Ardal included edu-cational parental support group meetings and individual par-ent-to-parent support (primarily telephone support)19 Measures used included the Parental Stressor Scale NICU the State and the Trait Anxiety Inventories and the Beck Depression Inven-tory After 4 months of participation mothers in the intervention group reported lower levels of stress state anxiety and depres-sion compared to control group mothers The authors speculated however that the participants who were able to meet face to face with other parents were those who benefited the most Hurst conducted a comprehensive survey of an NICU-based PSP This PSP was provided in a variety of formats including a weekly parent support group hospital visitation and 24-h telephone sup-port20 Of the 477 participants 303 families used the PSP dur-ing a 2-year evaluation period with 78 using only one form of support and 18 using two forms Of a sub-sample of 48 parents asked to complete an evaluation of the PSP 92 stated that they would recommend such a programme to other parents Furthermore the majority of parents felt that it made them feel supported and helped them deal with their emotions20 This is an indication that such programmes can be very successful in sup-porting parents throughout their infantrsquos hospitalization It also shows that it can be beneficial to give parents several options and formats when it comes to such support services It is impor-tant to consider though that both the Hurst and the Preyde and Ardal studies found that some participants did not find the sup-port programmes helpful even reporting that they had caused them increased stress and anxiety Therefore it should not be assumed that support programmes will suit every individual and will provide the required support for all parents1920 NICUs need to be flexible enough to provide parents with a range of forms of support to choose from
The increased understanding of the strains that parents of sick neonates have to deal with has also led to efforts to improve customary practices in NICUs Family-centred care focuses on infants and their needs and attempts to redefine the relationship between parents and caregivers These practices strive to provide parents with support during their infantrsquos illness by focusing on freely sharing information and on the collaboration between parents and hospital staff Family-centred care has been found to be associated with several beneficial outcomes including improved parental satisfaction increased parental comfort staff satisfaction and decreased parental stress18 Research is already examining these practices and questioning how these can be improved further Such research reflects the increasing effort focused on lsquohumanizingrsquo the environment in NICUs in order to make parents feel more comfortable about spending time with their infants
PaeDiaTrics anD cHilD HealTH 184 19
Conclusion
Surprisingly few interventions have prioritized the provision of emotional support for parents of sick neonates or accounted for the changing needs and wishes of parents over the course of their infantrsquos care Large-scale supportive education-based inter-ventions have been shown to be effective in reducing parental distress However the feasibility and sustainability of such pro-grammes should also be considered Programmes which require significant additional resources can be expensive and there are also issues of training and quality control Interventions which require significant input from parents may also place additional burdens on families making them potentially less accessible to those most at risk Arguably the aim should be to explore ways of providing acceptable and effective informational support which could be complemented by emotional support from health professionals and from other parents in the unit Increasingly studies are exploring the use of computers and multimedia as an engaging flexible and cost-effective method of targeting indi-vidual needs and providing support and information Such com-puter-based and interactive multimedia interventions have been found to be successful with a range of patient groups and could therefore be examined as a complementary method of providing informational support to families with sick neonates
REfEREnCEs
1 Glazebrook c Marlow n israel c et al randomised trial of a
parenting intervention during neonatal intensive care Arch Dis Child
Fetal Neonatal Ed 2007 92 F438ndash443
2 singer lT salvator a Guo s collin M lilien l Baley J Maternal
psychological distress and parenting stress after the birth of a very
low-birth-weight infant JAMA 1999 281 799ndash805
3 shaw rJ Deblois T ikuta l Ginzburg K Fleisher B Koopman c
acute stress disorder among parents of infants in the neonatal
intensive care nursery Psychosomatics 2006 47 206ndash212
4 Hopper a sources of stress for parents of a sick neonate a
literature review Pediatr Nurs 2000 30 29ndash32
5 Davis l edwards H Mohay H wollin J The impact of very
premature birth on the psychological health of mothers Early Hum
Dev 2003 73 61ndash70
6 Bernazzani O saucier J-F David H Borgeat F Psychosocial
predictors of depressive symptomatology level in postpartum
women J Affect Disord 1997 46 39ndash49
7 Field T infants of depressed mothers Infant Behav Dev 1995 18
1ndash13
8 Kaplan Ps Bachorowski J-a Zarlengo-strouse P child-directed
speech produced by mothers with symptoms of depression fails
to promote associative learning in 4-month-old infants Child Dev
1999 70 560ndash570
9 ward K Perceived needs of parents of critically ill infants in
a neonatal intensive care unit (nicU) Pediatr Nurs 2001 27
281ndash286
10 lai Hl chen cJ Peng Tc et al randomized controlled trial of music
during kangaroo care on maternal state anxiety and preterm infantsrsquo
responses Int J Nurs Stud 2006 43 139ndash146
8 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
11 Tallandini Ma scalembra c Kangaroo mother care and mother-
premature infant dyadic interaction Infant Ment Health J 2006 27
251ndash275
12 Ohgi s Fukuda M akiyama T Gima H effect of an early intervention
programme on low birthweight infants with cerebral injuries
J Paediatr Child Health 2004 40 689ndash695
13 Kaaresen Pi ronning Ja Ulvund se Dahl lB a randomized
controlled trial of the effectiveness of an early-intervention program
in reducing parenting stress after preterm birth Pediatrics 2006
118 e9ndash19
14 Melnyk BM Feinstein nF alpert-Gillis l et al reducing premature
infantsrsquo length of stay and improving parentsrsquo mental health
outcomes with the creating opportunities for parent empowerment
(cOPe) neonatal intensive care unit program a randomized
controlled trial Pediatrics 2006 118 e1414ndash1427
15 Jotzo M Poets cF Helping parents cope with the trauma of
premature birth an evaluation of a trauma-preventive psychological
intervention Pediatrics 2005 115 915ndash919
16 Pearson J andersen K evaluation of a program to promote positive
parenting in the neonatal intensive care unit Neonatal Netw 2001
20 43ndash48
17 roman l lindsay J Boger r et al Parent-to-parent support
initiated in the neonatal intensive care unit Res Nurs Health 1995
18 385ndash394
18 Meyer ec coll cTG lester BM Boukydis cFZ McDonough sM Oh w
Family-based intervention improves maternal psychological well-
being and feeding interaction of preterm infants Pediatrics 1994
93 241ndash246
PaeDiaTrics anD cHilD HealTH 184 19
19 Preyde M ardal F effectiveness of a parent ldquobuddyrdquo program for
mothers of very preterm infants in a neonatal intensive care unit
CMAJ 2003 168 969ndash973
20 Hurst i One size does not fit all Parentsrsquo evaluations of a support
program in a newborn intensive care nursery J Perinat Neonatal
Nurs 2006 20 252ndash261
Practice points
bull Parents of sick neonates experience significant distress and
exhibit higher levels of stress anxiety and depression than
parents of healthy infants
bull educational support emotional support and increased
motherndashinfant contact have been shown to promote maternal
well-being
bull emotional support for fathers has been largely neglected in
the research literature
bull Parents benefit from a choice of supportive facilities which
could include face-to-face sessions with health professionals
telephone support hospital visitation parent-to-parent
support and unit-based group support meetings
bull Parentsrsquo support needs can change during their infantrsquos
hospitalization and not all parents want or benefit from the
provision of additional information and emotional support in
the neonatal unit
9 copy 2008 elsevier ltd all rights reserved
Personal Practice
When should enteral feeds be started in preterm infantsnicholas D embleton
AbstractPaediatricians are regularly faced with the question of when best to start
enteral feeds in preterm infants this is important as longer term out-
come may be compromised by sub-optimal nutrition in early life clinical
factors that may affect the decision to start and the risk and benefits
are discussed
Keywords breast milk feeding nutrition parenteral nutrition
Key points in the history
Alice is lsquonutritionally vulnerablersquo and whilst this may not be immediately apparent it will affect her long term outcome Her energy stores are extremely limited and consist primarily of pro-tein She has less than 5 fat and little energy associated with stored glycogen She is losing about 1 gkgd protein equivalent so she needs at least that and a minimum of 50ndash60 kcalkg of energy just to maintain the status quo let alone grow
Her weight is on the 25th centile Review of any antenatal his-tory may reveal whether fetal growth was normal Fetal growth retardation can occur with a weight greater than 10th centile The presence of antenatal absent or reversed end diastolic flow in the umbilical artery indicates poor gut blood flow This increases the risk of necrotizing enterocolitis (NEC) and might suggest a more cautious approach to starting feeds1
She has no important cardiovascular problems but if she were hypotensive gut blood flow may be low There is no umbilical
Nicholas D Embleton BSC (Hons) MBBS (Hons) MD FRCPCH is Consultant in
Neonatal Medicine at Newcastle Neonatal Service Royal Victoria
Infirmary Newcastle upon Tyne NE1 4LP UK
Should you start feeds at a day of age
alice was born following spontaneous labour at 30 weeksrsquo
gestation she weighed 1300 g and is now 18 h old she was
briefly ventilated and then extubated to continuous positive
airway pressure 12 h ago in 35 oxygen she has had caffeine
citrate but still has intermittent episodes of self-correcting
apnoea she was commenced on iv 10 dextrose but this was
replaced by a parenteral amino acid solution (referred to as
lsquotPnrsquo) along with intralipid at 0900 this morning serum glucose
is 11 mmoll and blood pressure is 42 systolic
PaeDiatrics anD cHilD HealtH 184 20
arterial catheter in situ but there is no good evidence that this should delay the decision to start feeds Her glucose is high but this is quite common in a baby like this Could this be a sign of sepsis Caffeine does not affect the incidence of NEC2 The great-est risk factor for NEC in this case is prematurity
What else might be found on examination
Up until 24 h ago she was swallowing large amounts of amniotic fluid What will have changed since then
General examination should confirm peripheral perfusion lsquogestaltrsquo view (does she look lsquowellrsquo) and cardiovascular status lsquoBowel soundsrsquo are not usually helpful
The most important variable likely to affect gut perfusion is the arterial duct Precordial lsquoheaversquo and a loud murmur are sug-gestive but it is possible to have a significant ductal shunt in a baby with a normal examination Cardiac ultrasound will con-firm this diagnosis It might be better to treat a large shunt first with indometacin and to delay starting feeds for a further 24 h
It is not possible to assess gut perfusion clinically but normal perfusion elsewhere (adequate urine output usually indicates adequate renal perfusion) would be reassuring Most preterm babies have a few abdominal lsquoloopsrsquo visible but a distended abdomen with many palpable loops suggests ileus This might be secondary to sepsis or poor gut blood flow Preterm babies do not pass much meconium in the first 24ndash48 h
Balance of risks between starting and withholding feeds
Alice requires 35ndash4 gkgd of protein and 120 kcalkgd to grow3 This will initially be provided parenterally Delaying feeds increases the risk of gut villous atrophy and prolongs the need for lsquototal parenteral nutrition (TPN)rsquo TPN requires intravenous access and so increases the risk of sepsis and when prolonged use is required combined with the lack of enteral feeding may result in hepatic impairment
Delaying feeds may allow a gut that has been chronically under-perfused to re-establish more normal perfusion although normal gut endocrine function digestive enzyme upregulation and motility require a source of intraluminal nutrients1 A recent study suggested benefit from delaying the introduction of feeds4 but methodologi-cal problems exist5 Although a Cochrane meta-analysis suggested no benefit only two studies were included6 A large UK-based trial is examining the effect of early or late feeding in preterm infants who were born growth retarded following identification of antena-tal absent or reversed end diastolic flow in the umbilical artery7
When starting feeds what volume should be used
There are no good data to guide this decision We start with 24 mlkg (1 mlkgh) and then increase by this amount each day Most babies achieve full enteral feeds (ge150 mlkgd) by a week of age Feeding guidelines improve the outcome8 Measure-ment or assessment of gastric aspirates is not consistently useful in predicting subsequent feeding intolerance or development of NEC Aspirate volumes equivalent to or sometimes greater than the amount given in the preceding 1ndash2 h are usually normal Most aspirates have a greenish colour Thick bloody or intensely bile-stained aspirates require detailed assessment
0 copy 2008 elsevier ltd all rights reserved
Personal Practice
What else affects decisions and outcome
Feeding success is affected by sepsis and NEC Scrupulous atten-tion should be paid to hand washing and intravenous access and blood sampling should be minimized There is no good evidence to support the routine use of pro-kinetic agents or H2 blockers
The most important clinical intervention affecting the occur-rence of NEC is the use of breast milk9 All efforts should be directed at persuading parents of the benefits and supporting the process Some clinicians delay starting feeds for a further 24 h whilst expressed breast milk becomes available Donor breast milk might be equally efficacious10
RefeRenceS
1 Dorling J Kempley s leaf a Feeding growth restricted preterm
infants with abnormal antenatal Doppler results Arch Dis Child Fetal
Neonatal Ed 2005 90 F359ndash363
2 schmidt B roberts rs Davis P et al caffeine therapy for apnea of
prematurity N Engl J Med 2006 354 2112ndash2121
PaeDiatrics anD cHilD HealtH 184 20
3 embleton nD Pang n cooke rJ Postnatal malnutrition and growth
retardation an inevitable consequence of current recommendations
in preterm infants Pediatrics 2001 107 270ndash273
4 Berseth cl Bisquera Ja Paje VU Prolonging small feeding volumes
early in life decreases the incidence of necrotizing enterocolitis in
very low birth weight infants Pediatrics 2003 111 529ndash534
5 Menon G Boyle eM embleton nD et al introduction of enteral
feeds in preterm infants Pediatrics 2004 114 327ndash328
6 Kennedy Ka tyson Je chamnanvanikij s early versus delayed
initiation of progressive enteral feedings for parenterally fed low
birth weight or preterm infants Cochrane Database Syst Rev 2000
cD001970
7 wwwnpeuoxacukadept
8 Patole sK de Klerk n impact of standardised feeding regimens on
incidence of neonatal necrotising enterocolitis a systematic review
and meta-analysis of observational studies Arch Dis Child Fetal
Neonatal Ed 2005 90 F147ndash151
9 lucas a cole tJ Breast milk and neonatal necrotising enterocolitis
Lancet 1990 336 1519ndash1523
10 Boyd ca Quigley Ma Brocklehurst P Donor breast milk versus
infant formula for preterm infants systematic review and meta-
analysis Arch Dis Child Fetal Neonatal Ed 2007 92 F169ndash175
1 copy 2008 elsevier ltd all rights reserved
self-assessment
Case 1A term male infant born to consanguineous parents is assessed at 24 h of age due to poor feeding profuse yellow watery diar-rhoea and irritability He weighed 32 kg at birth and delivery was uneventful There was no polyhydramnios He has been breastfed since birth On examination he is pale with a non-tender but distended abdomen and reduced bowel sounds His weight is 275 kg and he looks dehydrated Examination is otherwise normal
Initial investigations (normal values in parentheses) showed
sodium 149 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 65 mmollitre (25ndash75)
creatinine 147 μmollitre (40ndash110)
chloride 119 mmollitre (95ndash105)
haemoglobin 172 gdl (140ndash200)
White blood cell count 80 times 109litre (100ndash260)
Platelet count 302 times 109litre (150ndash400)
arterial blood gas
ph 720 (730ndash745)
PcO2 23 kPa (46ndash60)
Bicarbonate 68 mmollitre (220ndash260)
Base excess minus186 mmollitre (minus20 to +20)
lactate 59 mmollitre (06ndash24)
An abdominal X-ray shows distended bowel loops with no intramural thickening or pneumoperitoneum (Figure 1)
He was given nil by mouth and received intravenous fluids and antibiotics His dehydration improved but the metabolic acidosis and diarrhoea persisted despite receiving no enteral feeds and the commencement of total parenteral nutrition Blood and stool cultures were negative
1 Which of the following best describes these results Choose ONE answer ONLY from the followingA Hypernatraemia hyperchloraemic metabolic acidosis
with increased anion gapB Hypernatraemia hyperchloraemic metabolic acidosis
with normal anion gap
Manish Sadarangani BM BCh MA MRCPCH is Clinical Research Fellow
at the Department of Paediatrics University of Oxford Centre for
Clinical Vaccinology and Tropical Medicine Churchill Hospital
Oxford OX3 7LJ UK
Shabna Rajapaksa MB BChir MA MRCPCH is Specialist Registrar in
Paediatrics at the Paediatric Intensive Care Unit John Radcliffe
Hospital Oxford OX3 9DU UK
Nicholas Mann MD FRCP FRCPCH DCH is Consultant Paediatrician at the
Department of Paediatrics Royal Berkshire Hospital Reading RG1
5AN UK
self-assessment
C Hypernatraemic dehydration and compensated metabolic acidosis
D Acute renal failureE Renal tubular acidosis
2 What is the likely diagnosis Choose ONE answer ONLY from the followingA Hirschsprung disease ndash long segmentB Cystic fibrosis with meconium ileusC Microvillus inclusion diseaseD Cowrsquos milk protein intoleranceE Lactose intolerance
3 What is the investigation of choice Choose ONE answer ONLY from the followingA Rectal biopsy with staining for acetylcholine receptorsB Immunoreactive trypsinC Gastrointestinal endoscopy and biopsyD Stool microscopy and cultureE Stool reducing substances
Case 2A 4-year-old boy presents with a 3 d history of jaundice and a florid rash He has had orange urine and there is no change in his stool colour His family originate from Kosovo and have lived in the UK for the last 8 years He has never left the UK There is no history of blood transfusion or sex-ual abuse The grandmother was recently diagnosed with hepatitis B
On examination he is well apyrexial and mildly jaundiced with cervical and axillary lymphadenopathy He has an exten-sive papular rash over the face extremities and trunk (Figure 2) There is 3 cm hepatomegaly with no splenomegaly or ascites Examination is otherwise normal
Figure 1 abdominal X-ray of baby
Paediatrics and child health 184 202 copy 2008 elsevier ltd all rights reserved
self-assessment
Initial investigations are as follows
haemoglobin 110 gdl (113ndash135)
White blood cell count 108 times 109litre (50ndash150)
Platelet count 278 times 109litre (150ndash400)
inr 10 (08ndash12)
aPt ratio 10 (08ndash13)
sodium 140 mmollitre (135ndash145)
Potassium 42 mmollitre (35ndash50)
Urea 56 mmollitre (25ndash75)
creatinine 65 μmollitre (45ndash120)
total bilirubin 66 μmollitre (0ndash15)
conjugated bilirubin 23 μmollitre (0ndash10)
alanine aminotransferase (alt) 2033 iUlitre (0ndash35)
alkaline phosphatase 987 iUlitre (71ndash234)
Gamma-glutamyl transferase (GGt) 870 iUlitre (0ndash51)
1 What is the name of this rash Choose ONE answer ONLY from the followingA Erythema multiformeB Erythema migransC GianottiminusCrosti syndromeD EczemaE Dermatitis herpetiformis
2 What is the most likely diagnosis Choose ONE Answer ONLY from the followingA Autoimmune hepatitisB Hepatitis BC Hepatitis DD Wilson diseaseE Alpha-1 antitrypsin deficiency
3 What is the best means of management Choose ONE answer ONLY from the followingA Isolation until the jaundice disappearsB ImmunosuppressionC Copper chelating agents and genetic counsellingD Patient and family education with consideration of
antiviral agentsE Liver transplantation
Case 3A 10-month-old boy presents with 3 weeks of vomiting and constipation ndash he is passing hard stools every 2ndash3 days He has fallen from the 9th to below the 04th centile in the last 6 weeks He passed meconium within the first 24 h of life On examina-tion he looks pale and there are some dysmorphic features ndash a short nose long philtrum and wide mouth He has normal heart sounds with a grade 3 ejection systolic murmur loudest at the upper right sternal edge Examination is otherwise normal
Initial investigations are as follows
haemoglobin 91 gdl (113ndash141)
total white blood cell count 124 times 109litre (60ndash170)
Platelet count 407 times 109litre (150ndash400)
sodium 144 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 78 mmollitre (25ndash75)
creatinine 78 μmollitre (45ndash120)
albumin 52 glitre (35ndash50)
corrected calcium 384 mmollitre (238ndash263)
Phosphate 167 mmollitre (099ndash157)
1 What is the most likely diagnosis Choose ONE answer ONLY from the followingA HyperparathyroidismB Acute leukaemiaC Williams syndromeD Hypervitaminosis DE Familial hypocalciuric hypercalcaemia
2 Which investigation would be most useful in establishing the diagnosis Choose ONE answer ONLY from the followingA Intact parathyroid hormone assayB Blood filmC Fluorescent in-situ hybridization for 7q1123 deletionD 25-hydroxyvitamin D assayE Urine calciumcreatinine ratio
3 Which of the following treatments would not be suitable for this patient Choose ONE answer ONLY from the followingA Low calcium dietB Normal saline infusionC FurosemideD CorticosteroidsE Bisphosphonates
Case 4A 10-week-old girl presents with a 2-day history of poor feed-ing Her mother has been concerned about weakness since birth She only has a flicker of movement in the arms none in the legs and has a weak cry She has been passing urine and opening her bowels normally She was born at full term by normal delivery and did not require any resuscitation at birth Normal fetal movements were felt antenatally and there was no polyhydramnios She is the first child of non- consanguineous parents and there is no significant family his-tory On examination she is alert and fixing and following appropriately She has a weak cry and a weak suck There is reduced central and peripheral tone with marked head lag
Figure 2 rash found on examination
Paediatrics and child health 184 203 copy 2008 elsevier ltd all rights reserved
self-assessment
Muscle power is grade 3 out of 5 in the arms and legs There is no muscle or tongue fasciculation and she has absent reflexes throughout The remainder of the examination is normal
Electromyogram shows irregular polyphasic motor unit potentials with marked instability consistent with a dener-vating and re-innervating process (Figure 3)
1 Which of the following additional investigations may be helpful Choose ONE answer ONLY from the followingA Nerve conduction studiesB Creatine kinase assayC Muscle biopsyD SMN1 gene analysisE All of the above
2 What is the most likely cause of this childrsquos symptoms Choose ONE answer ONLY from the followingA Congenital myotonic dystrophyB Duchenne muscular dystrophyC PraderminusWilli syndromeD Spinal muscular atrophyE Mitochondrial myopathy
3 What is the mode of inheritance of this disease Choose ONE answer ONLY from the followingA X-linked recessiveB Autosomal recessiveC Autosomal dominantD MitochondrialE Sporadic
Case 5A 13-year-old girl presents with a 3-week history of fever up to 40degC night sweats and headache She has a reduced appetite with some weight loss She has no other specific symptoms She was on holiday in China 7 months ago On examination she looks well and has a temperature of 387degC There is no lymphadenopathy and no rashes Examination is entirely normal
Results of investigations are as follows
haemoglobin 126 gdl (120ndash160)
total white blood cell count 132 times 109litre (43ndash108)
neutrophil count 115 times 109litre (25ndash75)
Platelet count 244 times 109litre (150ndash400)
Blood film neutrophilia with left shift
erythrocyte sedimentation rate 63 mmh (1ndash20)
c-reactive protein 219 mglitre (0ndash5)
Blood culture Streptococcus intermedius
from anaerobic bottle only
csf culture negative
Magnetic resonance imaging (MRI) of the brain shows acute frontal sinusitis with a large intracranial frontal extra-dural empyema (Figure 4)
1 Which of the following would be appropriate management Choose ONE answer ONLY from the followingA A 12-week course of intravenous antibioticsB Drainage of the frontal sinus followed by 2 weeks of
intravenous antibioticsC Drainage of the empyema followed by 2 weeks of
intravenous antibioticsD Drainage of the empyema and the frontal sinus
followed by 2 weeks of oral antibiotics
1151
1152
1153
1154
1155
1156
1157
1158
1159
1200
50ms 1mV
Figure 3 electromyogram recording from the patient Figure 4 Parasagittal section from mri scan of patient
Paediatrics and child health 184 204 copy 2008 elsevier ltd all rights reserved
self-assessment
E Drainage of the empyema and the frontal sinus followed by 8 weeks of intravenous antibiotics
2 Streptococcus intermedius is a potential pathogen in which of the following infections Choose ONE answer ONLY from the followingA Liver abscessB Urinary tract infectionC MeningitisD Thoracic empyemaE Pneumonia
3 Which of the following statements regarding lsquopyrexia of unknown originrsquo in children is false Choose ONE answer ONLY from the followingA Malignancy is the underlying pathology in 5ndash15 of
casesB An aetiology will be found in over 90 of casesC The most common cause is infectionD A rheumatological cause is found in 10ndash20 of casesE Familial Mediterranean fever can occur in children of
non-Mediterranean ethnicity
Answers
Case 11 AThe anion gap is a useful tool to differentiate the causes of a metabolic acidosis It is calculated by the equation
Anion gap = [Na K ] [Cl HCO ]3+ + minus minus+ minus +
It represents the effect of unmeasured anions on the plasma pH and is normally 10ndash18 mmollitre
2 CMicrovillus inclusion disease is a severe autosomal recessive enteropathy that is typically apparent within hours or days after birth It is the second most common cause of protracted diarrhoea in the newborn after infectious causes It is characterized by severe yellow watery diarrhoea and malabsorption due to hypoplasia andor atrophy of the villi of the small intestine secondary to an inherited defect in the brush border membrane This results in severe dehydration malnutrition and metabolic acidosis due to bicarbonate loss from the gut
3 CDiagnosis of microvillus inclusion disease is made on small bowel biopsy Electron microscopy findings are of intracellular brush border inclusions and densely packed apical cytoplasmic vesicular bodies indicating microvillous atrophy There is no cure Treatment is supportive with total parenteral nutrition and consideration of small bowel transplantation
Further reAding
Goulet O ruemmele f causes and management of intestinal failure
in children Gastroenterology 2006 130(suppl 1) s16ndash28
rhoads Jm Vogler rc lacey sr et al microvillus inclusion disease
In vitro jejunal electrolyte transport Gastroenterology 1991
100 811ndash817
Case 21 CGianottindashCrosti syndrome is a distinct self-limiting rash commonly associated with viral infections in children between 2 and 6 years of age It presents as multiple pink to redminusbrown papules or papulovesicles which may be pruritic and can become confluent Gianotti and Crosti initially described the exanthema as associated with hepatitis B virus and they termed it papular acrodermatitis of childhood It can occur in several viral diseases eg hepatitis A B and C coxsackie viruses and cytomegalovirus
2 BHepatitis is a syndrome characterized by inflammation or injury of liver cells which may develop into cell necrosis and subsequently fibrosis andor cirrhosis Biochemically there are raised liver enzymes The degree of transaminase elevation does not correlate with the severity of the disease process Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of viral hepatitis
3 DHepatitis B infection is transmitted via blood sexually or vertically Infection may be acute or chronic Diagnostic markers are the presence of surface antigen (HBsAg) and HBV DNA The presence of e antigen (HBeAg) indicates high infectivity Infected newborns have a 95 risk of becoming carriers this risk decreases with infection acquired later in childhood Approximately 15ndash25 of HBV carriers will die from cirrhosis or hepatocellular carcinoma Extrahepatic findings are more common in older children and include membranous glomerulonephritis and GianottiminusCrosti syndrome Fulminant hepatic failure occurs in severe cases resulting in persistent jaundice encephalopathy and coagulopathy Management includes counselling family members monitoring for ongoing liver disease and consideration of antiviral therapy
Further reAding
Brandt O abeck d Gianotti r Burgdorf W Gianotti crosti
syndrome J Am Acad Dermatol 2006 54 136ndash145
slowik mK Jhaveri r hepatitis B and c viruses in infants and
young children Semin Pediatr Infect Dis 2005 16 296ndash305
Case 31 CHypercalcaemia is uncommon in infancy The most common symptoms in this age group are irritability vomiting and constipation It may be a manifestation of Williams syndrome vitamin D or calcium excess as well as disorders associated with reduced bone formation such as hypophosphatasia or increased bone resorption such as malignancy Occasionally
Paediatrics and child health 184 205 copy 2008 elsevier ltd all rights reserved
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-
SympoSium neonatology
Acidndashbase physiology and blood gas interpretation in the neonateSusern tan
morag Campbell
Abstractacidndashbase balance describes the complex processes that work to main-
tain a stable extracellular pH for optimal cellular function the process
of balancing the production and neutralization of tissue acid provides a
great challenge for newborn infants who have significantly higher rates
of acid production than adults Factors which help maintain a stable
acidndashbase balance include buffers the respiratory system and renal sys-
tem Both intracellular and extracellular buffers resist changes in pH
the most important extracellular buffer system for maintaining stable
pH is the bicarbonate system in response to acidosis or alkalosis the
respiratory system balances the production of acid with the clearance
of Co2 by altering respiratory rate the kidneys provide a delayed but
sustained response to pH imbalance by excreting either acidic or alkaline
urine in response to systemic acidosis and alkalosis respectively in sick
premature infants these systems have a limited capacity completely to
control pH this review discusses the physiology of the three systems
which control acidndashbase balance patterns of clinical abnormalities in
acidndashbase status and their underlying causes are discussed We present
a systematic approach to blood gas analysis and interpretation in new-
born infants
Keywords acidosis alkalosis bicarbonate bloodndashgas analysis
metabolic pH
Introduction
Blood gas analysis is a routine procedure performed on newborn babies receiving respiratory support in the neonatal intensive care The combination of invasive and non-invasive assessment of ventilation and oxygenation enables clinicians appropriately to modify respiratory care according to each individual babyrsquos rapidly changing clinical status
Understanding the fundamentals of acidndashbase balance helps us to use blood gas analysis not only to assess respiratory sta-tus but also to provide information on metabolic status and the adequacy of tissue perfusion
Susern Tan MBBS MRCP is Clinical Fellow at the Neonatal Intensive Care
Unit 6th Floor North Wing St Thomasrsquo Hospital London SE1 7EH UK
Morag Campbell MBChB MRCP is Consultant Neonatologist at the
Neonatal Intensive Care Unit 6th Floor North Wing St Thomasrsquo
Hospital London SE1 7EH UK
paeDiatRiCS anD CHilD HealtH 184 17
What is understood by acid-base balance
Acidndashbase balance refers to the complex physiological processes used by the body to maintain a stable extracellular pH1 A serum pH within the range of 735ndash745 provides the ideal environment for cellular metabolism Maintaining a stable pH is critical as the metabolic activity of proteins is pH dependent and small changes in hydrogen ion (H+) concentration can potentially alter physio-logical function
Acids are substances that yield free H+ in solution while a base accepts H+ and in solution combines with an acid to neu-tralize it In the normal metabolic state H+ are continuously pro-duced and neutralized to maintain a steady pH balance12 The rate of H+ production is two to three times higher in neonates because of their rapid growth rates and increased acid production from protein turnover and bone mineralization The challenge of maintaining a stable pH through processing and neutralizing H+ is therefore greatest in newborn infants
Using exact values of H+ concentration to assess acidndashbase status is cumbersome and it is more commonly expressed as pH defined by the equation
pH = minuslog H+
Maintaining acidndashbase balance
The balance between production and excretion of acids in the body is controlled by buffer systems which have an immediate effect and by the respiratory and the renal systems
Buffer systemsBuffer solutions resist change in pH when acid or alkali is added due to their capacity to absorb or give up H+ The three main buffer systems in the body are the bicarbonate phosphate and protein systems1ndash3 The protein and phosphate buffer systems are intracellular and act as lsquosinksrsquo for extracellular H+ which are exchanged with intracellular potassium (K+) and sodium ions (Na+) In an acute metabolic acidosis hyperkalaemia may develop due to this H+ exchange4
The bicarbonate buffer system is extracellular and consists of a mixture of carbonic acid (H2CO3) and sodium bicarbon-ate (NaHCO3) This buffer system helps maintain a stable pH by soaking up excess H+ with HCO3
minus which in solution forms carbonic acid (H2CO3) Carbonic acid is a weak acid and readily dissociates to give CO2 which is transported in dissolved form to the lungs for excretion
H+ + HCO3minus harr H2CO3 harr H2O + CO2
The bicarbonate system therefore completes the neutraliza-tion of excess H+ and a stable plasma pH is maintained The relationships between pH HCO3
minus and CO2 in this system are described by the HendersonndashHasselbalch equation15
pH = 61 + log HCO3minus003 times CO2
where 61 is the log of the dissociation coefficient of carbonic acid and 003 the solubility of CO2 in plasma Buffers are most potent when there are equal amounts of H+ and HCO3
minus in solution The
2 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
bicarbonate system is not a potent buffer however as HCO3minus
and CO2 are readily altered by the body this system plays a very powerful role in pH homeostasis15
Respiratory regulationThe respiratory system adapts within minutes to hours as part of the acute response to acidosis This system modifies pH by balancing production of H+ with ventilatory clearance of CO2
H+ directly stimulates chemoreceptors in the respiratory cen-tre of the brainstem producing an increase in respiratory rate26 The response to respiratory acidosis is very rapid as CO2 easily diffuses across the bloodndashbrain barrier however in metabolic acidosis compensation is delayed until plasma bicarbonate fully equilibrates with cerebrospinal fluid (CSF) bicarbonate There is an inverse relationship between alveolar ventilation and partial pressure of dissolved carbon dioxide (PaCO2) a reduction in alveolar ventilation raises PaCO2 and decreases pH Changes in pH therefore affect alveolar ventilation and conversely changes in alveolar ventilation cause significant changes in pH
Renal regulationThe kidneys provide a delayed but sustained response to acidndashbase imbalances by excreting either acidic or alkaline urine In full-term and preterm babies the capacity for acid excretion and bicarbonate reabsorption is reduced as glomerular filtration rates are low and tubular function immature7 Renal function matures with gestation postnatal age and glucocorticoid and thyroid hormones78 Due to their limited capacity to preserve HCO3
minus newborn infants have lower serum bicarbonate levels and are predisposed to acidosis7
Bicarbonate is not effectively reabsorbed due to its size and electrical charge Instead intraluminal HCO3
minus combines with secreted H+ in tubular luminal fluid to produce carbonic acid which dissociates to give H2O and CO2 This CO2 diffuses into tubular cells combines with intracellular H2O and forms carbonic acid which liberates HCO3
minus and H+ HCO3minus is then
recovered to the circulation by exchange for chloride ions (Clminus) through the basal cell membrane247
Renal acid secretion occurs at all sites except the loop of Henle Primary active transport accounts for 5 and secondary for the remaining 95 of total H+ excretion Secondary trans-port involves an exchange between luminal Na+ and intracel-lular H+ Both ions bind to a membrane transport protein The Na+ concentration gradient between the tubular lumen and cells enables Na+ drag into the cell which generates energy to fuel active H+ excretion into the tubular lumen1ndash47
Quantifying acidosis
Standard base excess is a calculated value derived from PaCO2 and pH It is expressed as the mmollitre of base above or below normal buffer bases required to correct the pH to 74 at a PaCO2 of 40 mmHg A negative base excess or base deficit indicates an acidosis while a positive base excess indicates a relative alkalosis15
Anion gap is the measured difference between anions and cations in the blood
Anion gap = (Na+ + k+) minus (HCO3+Clminus)
paeDiatRiCS anD CHilD HealtH 184 17
Calculation of the anion gap enables clinicians better to define the underlying cause of a metabolic acidosis9 The common causes of an increased anion gap acidosis in neonates include lactic acidosis due to tissue hypoperfusion and hypoxia it may also be seen with certain inborn errors of metabolism and in uraemia910 The anion gap can help distinguish between the rela-tively benign non-anion gap hyperchloraemic acidosis seen in premature infants and a pathological lactic acidosis due to poor end-organ perfusion1011
Strong ion theory
Stewart described a complex acidndashbase model which proposed that H+ concentration results from the dissociation of water which is influenced by PaCO2 the strong ion difference and plasma weak acids12
Strong ions are ions that dissociate at normal body pH and include Na+ K+ and Clminus Weak acids in plasma which contrib-ute include albumin inorganic phosphate and plasma proteins their concentrations do not change with pH and are therefore a constant The effect of these factors and other unmeasured tissue ions on acidndashbase status can be quantified by the calculation of the strong ion gap (SIG)112 In the neonatal unit it is perhaps more important that we consider how principles of this model may relate to acidndashbase status rather than fully to quantify the SIG Theoretically low albumin and phosphate levels which fre-quently occur in premature infants by reducing the concentra-tion of weak acids can produce a relative alkalosis while high phosphate levels in renal failure may contribute to acidosis
Tissue oxygenation
Oxygenation is closely linked to acidndashbase status as optimal cel-lular function requires oxygen to fuel aerobic metabolism and produce energy In hypoxic conditions anaerobic metabolism predominates which is energy inefficient and results in a lactic acidosis1011
Tissue oxygen availability is related to regional blood flow haemoglobin level and haemoglobin oxygen affinity Arterial blood gases measure the partial pressure of dissolved oxygen (PaO2) which represents a small component of total oxygen con-tent the majority being transported bound to haemoglobin The relationship between percentage haemoglobin saturation (SaO2) and PaO2 is described by the sigmoidal oxyhaemoglobin disso-ciation curve which enables us to relate the two measures to each other235 The affinity of haemoglobin for oxygen is altered by local tissue factors Increases in temperature H+ PaCO2 and 23-diphosphoglycerate (DPG) levels shift the oxyhaemoglobin dissociation curve to the right reducing affinity for oxygen Decreases in temperature H+ PaCO2 and 23-DPG levels shift the curve to the left increasing oxygen affinity1ndash35 In the body haemoglobin oxygen affinity continuously changes increasing in the lungs to enable efficient oxygen uptake and decreasing at tissue level to provide efficient oxygen delivery to metabolically active tissues
Avoiding both hypoxia and hyperoxia is important in the neo-natal unit as deleterious effects of hypoxia are seen in infants with pulmonary hypertension1314 while hyperoxia is associated with an increased incidence of retinopathy of prematurity1516
3 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Clinical acidndashbase imbalances
Clinical acidndashbase imbalances can be respiratory metabolic or a mixture of both These abnormalities may be corrected by the acidndashbase regulatory mechanisms in the body in an attempt to maintain normal pH (Figure 1)
Respiratory acidosisThis occurs when any disorder leads to decreased alveolar ventilation Common causes of respiratory acidosis are listed in Table 1 Reduced respiratory clearance of CO2 means more dissolved CO2 accumulates in the plasma leading to increased production of carbonic acid and H+ Through chemoreceptor stimulation respiratory acidosis rapidly alters ventilation in an attempt to reduce CO226 Chemoreceptor mediated ventila-tory increases may only partly adjust in premature infants with underlying lung disease In babies with a sustained respiratory acidosis eg in chronic lung disease then metabolic compen-sation occurs through increased renal excretion of H+ and reabsorption of HCO3
minus slowly restoring pH to around 80 of normal47
paeDiatRiCS anD CHilD HealtH 184 17
The management of PaCO2 levels in infants receiving mechan-ical ventilation has important clinical implications Premature babies have impaired cerebral autoregulation17 and adverse neurological sequelae are reported in association with high PaCO2 levels18ndash20 Ventilation strategies which advocate lsquoper-missive hypercarbiarsquo have been developed to minimize airways damage from mechanical ventilation21 Published data suggest pulmonary benefits however the safe level of PaCO2 remains to be defined in premature infants2021
Respiratory alkalosisThis occurs when more CO2 is excreted than is produced by the body Pathological conditions leading to respiratory alkalosis are rare Hyperventilation in the neonatal setting is often iatrogenic or may be due to disorders in brainstem control of breathing including hypoxicndashischaemic encephalopathy or primary central nervous system abnormalities (see Table 1)
If respiratory alkalosis is sustained it may be compensated for by reduced reabsorption of filtered bicarbonate Reported adverse associations of low PaCO2 include periventricular leuco-malacia and intraventricular haemorrhage1922
K+
H+
Overventilation
CO2 + H2O harr H2CO3 harr H+ + HCO3ndash
Bicarbonate Buffer
Intracellular Buffer
uarr H+ excretionuarr HCO3
ndash absorption
uarr buffered H+
(NH4+ H2PO4
ndash)uarr ventilation rate
RespiratoryAcidosis
MetabolicAcidosis
darr CO2and uarr pH
RespiratoryAlkalosis
MetabolicAlkalosis
darr H+ anduarr pH
darr ventilation rate
uarrCO2
and darr pH
darr H+ excretiondarr HCO3
ndash absorption
uarrH+ and
darr pH
Brain
Brain
Intracellular Buffer
H+
K+
Sepsis
HypoxiaRDS
Metabolismand growth
Diuretics
Airwayobstruction
Neuromuscularproblems
IEM
Gastric losses
+ +
ndash -
Renal BufferRespiratory Buffer
Figure 1 mechanisms for regulation of extracellular pH iem inborn errors of metabolism RDS respiratory distress syndrome
4 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Common causes of acidndashbase imbalances
pH PCO2 H2CO3 Base excess Common neonatal causes
Respiratory acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
uarr normal normal bull upper airway obstruction choanal atresia
pierre-Robin sequence
bull lung abnormalities respiratory distress
syndrome transient tachypneoa of
newborn pneumonia meconium aspiration
syndrome pulmonary hypoplasia
congenital pulmonary malformations
bull Central hypoventilation hypoxic-ischaemic
encephalopathy intracranial haemorrhage
bull neuromuscular insufficiency congenital
myopathies congenital neuropathies
bull iatrogenic inadequate ventilatory settings
Compensated lower limit
of normal
uarr uarr gt+3
metabolic acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
normal darr ltminus3 increased anion gap
bull lactic acidosis sepsis hypoperfusion
shock necrotizing enterocolitis
bull inorganic acidosis inborn errors of
metabolism renal failure
normal anion gap
bull increased gastrointestinal H2Co3 losses
ileostomy diarrhoea
bull Renal tubular acidoses
Compensated lower limit
of normal
darr darr ltminus3
Respiratory alkalosis Uncompensated gt 745 darr normal normal bull iatrogenic excessive ventilatory settings
bull Compensatory hyperventilation hypoxic-
ischaemic encephalopathy
Compensated higher limit
of normal
darr darr ltminus3
metabolic alkalosis Uncompensated gt 745 normal uarr gt+3 bull gastric losses vomiting non-replacement
of excessive nasogastric aspirates
bull thiazide and loop diuretics
bull Hypokalaemia
Compensated higher limit
of normal
uarr uarr gt+3
Table 1
Metabolic acidosisThis frequently affects infants in the neonatal unit and has many causes1011 (see Table 1) There may be overproduction of tissue acid impaired acid clearance gastrointestinal loss of bicarbonate or an exogenous increased acid load eg chloride total paren-teral nutrition (TPN) or albumin1ndash323
Calculation of the anion gap to distinguish an increased anion gap acidosis from a non-anion gap acidosis is important both for treatment and prognosis1011 Acidosis stimulates respiratory compensation but this is limited in unstable infants Similarly renal compensation with improved HCO3
minus conservation is con-strained by tubular immaturity Treatment of the acidosis should be directed at the underlying cause eg hypoxia hypotension or excess Clminus rather than by administration of base
Metabolic alkalosisThis is unusual in neonates and is most frequently seen in infants with chronic lung disease or heart failure who are receiving diuretics Diuretics cause alkalosis by increasing renal fluid and Na+ losses An active process to reabsorb Na+ occurs in tubule cells which through enhanced H+ secretion and HCO3
minus reab-sorption produce alkalosis27
paeDiatRiCS anD CHilD HealtH 184 17
Metabolic alkalosis may also occur with excessive loss of gas-tric contents eg protracted vomiting or inadequate replacement of nasogastric aspirates (see Table 1)
Interpreting blood gases
Blood gas measurements can provide important diagnostic and prognostic information and a systematic approach to blood gas analysis is described in Table 2 The clinical management of infants with abnormal gases requires a good understanding of acidndashbase physiology and tissue oxygenation and an apprecia-tion of factors which may affect the reliability of samples
Arterial blood sampling is the gold standard however indwelling arterial catheters and arterial stab samples are usually restricted to infants who are critically ill or those who require sig-nificant ongoing intervention Gases are most frequently measured in capillary or venous samples which correlate well with arterial samples for PaCO2 pH and base excess in babies and children receiving intensive care These correlations however are not valid in infants with peripheral vasoconstriction and hypotension2324
Non-invasive monitoring techniques may enable us to reduce the frequency of blood gas sampling Transcutaneous monitoring
5 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
A systematic approach to blood gas analysis
1 Collect the relevant information
bull type of gas ndash capillary or arterial
bull Current respiratory support ndash document level
bull transcutaneous Co2 and Sao2 levels
bull Clarify no significant clinical events before sampling
2 pH accept a range between 730 and 745 in newborn
babies this is lower than in older children is there an
alkalosis (pH gt 745) or an acidosis (lt 730)
3 Co2 aim for a range between 45 and 65 kpa a paCo2 level
more than 65 kpa suggests inadequate alveolar ventilation
while less than 45 kpa suggests hyperventilation Correlate
values with non-invasive measures
4 o2 Can only be assessed from arterial gases aim for pao2
between 60 and 80 kpa Correlate results with pulse
oximetry levels
5 HCo3 and base excess normal HCo3 level is between 20 and
24 mmollitre and bases excess +3 to minus3
6 anion gap look at the anion gap and lactate to help identify
the cause of an acidosis normal lactate levels should be less
than 2 mmollitre
7 Respiratory or metabolic compensation look at the pH and
assess whether it is appropriate for the Co2 level or is there
evidence of compensation
8 interpret use both the clinical history and blood gas
findings to help you identify the primary problem aim your
management at treating the underlying cause
9 Reassess if clinical management changes have been made
repeat the blood gas after an appropriate time interval to
ensure improvement
Table 2
provides a highly accurate and reliable method for measuring PaCO2 through the skin it can however be technically difficult may cause tissue damage and is of limited reliability when peripheral perfusion is reduced25 Continuous end-tidal CO2 measurements correlate well with arterial CO2 values in patients with normal ventilation and perfusion however in babies with lung disease alveolar collapse small tidal volumes and rapid respiratory rates can make these measurements unreliable26 Despite its limitations transcutaneous monitoring provides the best method for CO2 trend monitoring in the neonatal intensive care unit (NICU)25
Oxygen saturation levels can be continuously measured non-invasively using pulse oximetry While oximetry is easy to perform and accurate on occasion SaO2 levels obtained may be unreliable when tissue perfusion is poor or with movement artefact SaO2 monitoring is highly sensitive at detecting hypoxia but is limited in detecting hyperoxia as at levels more than 90 small changes in SaO2 may result in unacceptably large increases in PaO227 It is therefore essential that SaO2 alarm limits are set for all neonates receiving respiratory support to detect hypoxia and prevent hyperoxia1627
Continuous non-invasive monitoring provides invaluable information when managing complex infants in the NICU but it does not replace the need for regular blood gas analysis
paeDiatRiCS anD CHilD HealtH 184 17
ReFeRenCeS
1 Kellum Ja Determinants of blood pH in health and disease
Crit Care 2000 4 6ndash14
2 Quigley R Baum m neonatal acid base balance and disturbances
Semin Perinatol 2004 28 97ndash102
3 Brouillette Rt Waxman DH evaluation of the newbornrsquos blood gas
status Clin Chem 1997 43 215ndash221
4 Chan JC acid-base disorders and the kidney Adv Pediatr 1983 30
401ndash471
5 Siggaard-andersen o the pH-log pCo2 blood acidndashbase nomogram
revised Scand J Lab Invest 1962 14 598ndash604
6 Saetta m mortola Jp interaction of hypoxic and hypercapnic stimuli
on breathing pattern in the newborn rat J Appl Physiol 1987 62
506ndash512
7 Baum m Quigley R postnatal renal development in Seldin DW
giebisch g eds the kidney physiology and pathophysiology new
york lippincott Williams and Wilkins 2000 p 703ndash726
8 ortiz la Quan a Weinberg a et al effect of prenatal
dexamethasone on rat renal development Kidney Int 2001 59
1663ndash1669
9 gabow pa Kaehny WD Fennessey pV goodman Si gross pa
Schrier RW Diagnostic importance of an increased serum anion gap
N Engl J Med 1980 303 854ndash858
10 lorenz Jm Kleinman li markarian K oliver m Fernandez J Serum
anion gap in the differential diagnosis of metabolic acidosis in
critically ill newborns J Pediatr 1999 135 751ndash755
11 Deshpande Sa platt mp association between blood lactate and
acid-base status and mortality in ventilated babies Arch Dis Child
1997 76 F15ndash20
12 Stewart pa modern quantitative acid-base chemistry Can J Physiol
Pharmacol 1983 61 1444ndash1461
13 Dakshinamurti S pathophysiologic mechanisms of persistent
pulmonary hypertension of the newborn Pediatr Pulmonol 2005
39 492ndash503
14 mourani pm ivy DD gao D abman SH pulmonary vascular
effects of inhaled nitric oxide and oxygen tension in
bronchopulmonary dysplasia Am J Respir Crit Care Med 2004
170 1006ndash1013
15 Deulofeut R Critz a adams-Chapman i Sola a avoiding hyperoxia
in infants le 1250 g is associated with improved short- and long-
term outcomes J Perinatol 2006 26 700ndash705
16 Chow lC Wright KW Sola a Can changes in clinical practice
decrease the incidence of severe retinopathy of prematurity in very
low birth weight infants Pediatrics 2003 111 339ndash345
17 Boylan gB young K panerai RB Rennie Jm evans DH Dynamic
cerebral autoregulation in sick newborn infants Pediatr Res 2000
48 12ndash17
18 Kaiser JR gauss CH pont mm Williams DK Hypercapnia during
the first 3 days of life is associated with severe intraventricular
hemorrhage in very low birth weight infants J Perinatol 2006 26
279ndash285
19 Fabres J Carlo Wa phillips V Howard g ambalavanan n Both
extremes of arterial carbon dioxide pressure and the magnitude of
fluctuations in arterial carbon dioxide pressure are associated with
severe intraventricular hemorrhage in preterm infants Pediatrics
2007 119 299ndash305
20 thome uH Carroll W Wu tJ et al outcome of extremely preterm
infants randomized at birth to different paCo2 targets during the
first seven days of life Biol Neonate 2006 90 218ndash225
6 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
21 Carlo Wa Stark aR Wright ll et al minimal ventilation to prevent
bronchopulmonary dysplasia in extremely-low-birth-weight infants
J Pediatr 2002 141 370ndash374
22 okumura a Hayakawa F Kato t et al Hypocarbia in preterm
infants with periventricular leukomalacia the relation between
hypocarbia and mechanical ventilation Pediatrics 2001 107
469ndash475
23 peters o Ryan S matthew l Cheng K lunn J Randomised
controlled trial of acetate in preterm neonates receiving parenteral
nutrition Arch Dis Child 1997 77 F12ndash15
24 yildizda D yapiciolu H yilmaz Hl Sertdemir y Correlation of
simultaneously obtained capillary venous and arterial blood gases
of patients in a paediatric intensive care unit Arch Dis Child 2004
89 176ndash180
25 aliwalas ll noble l nesbitt K et al agreement of carbon
dioxide levels measured by arterial transcutaneous and end tidal
methods in preterm infants 28 weeks gestation J Perinatol 2005
25 26ndash29
26 Hagerty JJ Kleinman me Zurakowski D et al accuracy of a new
low-flow sidestream capnography technology in newborns a pilot
study J Perinatol 2002 22 219ndash225
paeDiatRiCS anD CHilD HealtH 184 17
27 poets CF Wilken m Seidenberg J Southall Dp von der Hardt H
Reliability of a pulse oximeter in the detection of hyperoxemia
J Pediatr 1993 122 87ndash90
Practice points
bull a stable extracellular pH is important for optimal cellular
functioning
bull abnormalities in acidndashbase balance are regulated by buffer
systems and the respiratory and renal tract
bull maintaining a stable pH is challenging for newborn babies
due to their high rates of acid production and immature
regulatory mechanisms
bull arterial or capillary blood gases provide an effective way to
monitor acidndashbase balance in newborns
bull Blood gases should be analysed in a structured manner
assessing pH and then respiratory and metabolic components
bull the treatment of acidndashbase abnormalities should be directed
at the underlying problem not merely at correcting pH
7 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Recognition and management of neonatal seizuresmalcolm levene
AbstractSeizures are the most common major manifestation of central nervous
system dysfunction in the newborn there are many causes but perina-
tal asphyxia and haemorrhagicinfarction lesions account for about 75
there is now considerable evidence that frequent but short seizures in
the neonate affect subsequent neurodevelopmental outcome Studies
using eeg or modified continuous tracing of eeg activity (aeeg or CFm)
have shown that there is often electroconvulsive dissociation this re-
fers to poor correlation between electrical seizures and clinical seizures
Commonly used anticonvulsants appear to increase electroconvulsive
dissociation effective management of neonatal seizures has proved very
disappointing and less than 50 of seizures are abolished by first-line
anticonvulsant medication (phenobarbitone or phenytoin) Drugs such
as midazolam and lidocaine may further reduce seizures but require
more evaluation the challenge is to assess new and more effective anti-
convulsants which are themselves associated with little neurotoxicity
Keywords antiepileptic drugs eeg neonatal seizures neurodegeneration
Convulsions are the most common major neurological sign seen in newborn infants and their incidence estimated from large population studies is 26 per 1000 live births1 Premature infants are over four times more likely to have convulsions than full-term infants12 Neonatal status epilepticus (continuous seizure activity lasting 30 min or more) diagnosed clinically is rare and accounts for only 5 of infants with seizures1 although this is now recognized more frequently as the result of continuous EEG monitoring3
Neonatal convulsions are described as presenting in a num-ber of different ways and various seizure types can be seen in the same baby over a number of hours The frequencies of the various patterns of seizure activity are given in Table 1 In very premature babies and to a lesser extent in term infants minor movement abnormalities may be difficult to identify as subtle seizures These include lip smacking tongue thrusting mouth-ing pedalling type movements of the lower limbs or swimming movements of the arms Apnoea can be a common manifesta-tion of subtle seizures The signs can be protean and vary from baby to baby or even in the same baby Virtually any stereotypic
Malcolm Levene MD FMedSc FRCPCH FRCH is Professor and Head of
Department of Paediatrics and Child Health at University of Leeds Leeds
and Honorary Neonatologist at Leeds General Infirmary Leeds UK
paeDiatRiCS anD CHilD HealtH 184 178
movement may be a manifestation of a seizure disorder in the newborn
Aetiology
The more carefully the fitting baby is investigated the more likely it is that a cause for the seizures will be found A number of recent papers have described the aetiology of neonatal con-vulsions after extensive investigations14 Tekgul et al4 recently studied a consecutive group of full-term infants with evidence of neonatal convulsions (recognized both clinically and on EEG) and reported their outcome Table 2 summarizes these data as well as risk of moderate or severe disability for each causative factor Perinatal asphyxia is the commonest cause for convul-sions in term infants with haemorrhagic or ischaemic lesions also being common
Overall the prognosis for the group of term babies with con-vulsions was good 72 had a favourable outcome Where asphyxia (hypoxicndashischaemic insult) is the cause of neonatal convulsions the outcome is poor in 50 The prognosis for neonatal convulsions when they were due to arterial or cere-brovenous infarction or intracranial haemorrhage was generally good Individually inborn errors are a very rare cause of neo-natal convulsions but in view of the treatable nature of some of these it is essential that these be considered and investigated appropriately5
Patterns of seizure activity in the newborn
Movement pattern Frequency ()
Clonic 50
tonic 20
Subtle 10ndash35 depending on maturity
myoclonic 5
Table 1
Cause incidence and outcome of neonatal convulsions in term infants14
Aetiological factor Incidence () Poor outcome ()
asphyxia 38ndash40 50
Cerebral arteriovenous
infarction
20 0
intracranial haemorrhage 12ndash20 13
Congenital cerebral anomaly 5ndash10 100
Hypoglycaemiahypocalcaemia 3ndash19
infection 3ndash20
inborn error of metabolism 1
unknown cause 10ndash13 0
Refers to moderate and severe neurodevelopmental abnormalitynumbers too small to make meaningful predictions
Table 2
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Controversies in the clinical management of neonatal seizures
In recent years we have learnt much more about the neurobi-ology of seizures and their effect on the developing brain The neonatal brain is in a neurophysiologically hyperexcitable state compared to the more mature brain and therefore is more prone to seizure activity This is due largely to a relative excess of GABA neuroreceptors GABA receptors are usually inhibitory but in the immature brain they have a paradoxically excitatory effect This changes at about term in primates and with progressive develop-ment they adopt a neuroinhibitory role6
The propensity to seizures in the neonatal brain makes resolv-ing the balance of risks between continuing seizure activity on the one hand against potentially adverse effects of therapy on the other a very important equation Added to this is the problem of accurately diagnosing neonatal seizures and whether commonly used anticonvulsants are successful in controlling them
These conundrums can be posed as a series of challenging questions which are discussed below
Do neonatal convulsions cause brain injuryConvulsions are a sign of neurological compromise and may indi-cate significant underlying structural brain damage or biochemi-cal disturbance which may cause further brain damage in its own right There has been considerable debate about the scale of the disability that convulsions cause the immature brain over and above that due to the underlying cause Most of our knowledge comes from studies in rodents and these have provided some tentative answers to this question
Seizures in the mature brain lead to neuronal necrosis but studies in very young rat pups whose brain development is somewhat similar to full-term infants have shown that a series of five brief seizures on five successive days does not cause struc-tural neuronal damage but does produce morphological changes in hippocampal neurones and worryingly deficits in the rat learning and visual spatial memory function in adolescent and adult life7 A single prolonged neonatal convulsion in similarly immature rats does not produce any functional effects8 Others have shown that following priming of the neonatal rat brain by short seizures as described above a further insult comprising induction of status epilepticus in the same rats at an older age causes neuronal necrosis9 This has been referred to as the lsquotwo hit hypothesisrsquo10
A more specific question is does seizure activity in an already significantly compromised brain cause additional neuropathol-ogy Wirrell et al11 studied a series of immature rat pups with the induction of an hypoxicndashischaemic (asphyxial) insult fol-lowed by either chemically-induced fits or a control sham pro-cedure In the more severely asphyxiated animals the degree of brain damage was increased significantly in those that had the additional burden of induced seizures
In summary these studies show that the immature brain is more resistant to short frequent post-seizure damage than the mature brain but despite resulting in no loss of neuronal numbers the function of the brain is permanently affected in later life In the asphyxiated brain seizures appear to have an additional adverse effect on brain damage Furthermore the immature brain that has been lsquoprimedrsquo by early seizures is more
paeDiatRiCS anD CHilD HealtH 184 179
vulnerable to status epilepticus later in life It would appear from these data that frequent seizures in the human infant should be stopped and this begs the question as to whether currently used anticonvulsants effectively control neonatal seizures
Can we rely on clinical versus EEG diagnosis of neonatal convulsionsTraditionally the diagnosis of neonatal convulsions has been made by observation and description of the frequency of abnor-mal movements EEG has been technically difficult in the hostile electrical activity of a neonatal intensive care environment and considerable expertise is required for analysis of the trace It is usually not practical to undertake traditional EEG recordings at the time the baby shows abnormal movements More recently various technological developments have allowed more direct investigation of neuronal electrical activity by either video-EEG or compressed recording of the amplitude integrated EEG (aEEG or CFM)
Rennie et al3 at Kingrsquos College Hospital London have under-taken extensive evaluation of video-EEG and have found that this technique detects many convulsions not recognized by a single channel aEEG or CFM trace Of 19 infants with evidence of convulsions on EEG only four were recognized on CFM but this may have been due to the observersrsquo lack of experi-ence with this technique In other centres that have developed appropriate expertise aEEG or CFM has proved more sensitive to the detection of seizures Video-EEG studies have also shown that many movements interpreted by experienced clinicians to be seizures are not associated with abnormal cortical activity Conversely many electrical seizures are not associated with abnormal movements This is referred to as electroconvulsive dissociation
In summary clinical observation alone to detect the fitting baby is unreliable in that it may either over-detect seizure activ-ity which is not present on EEG or under-detect clinical seizures in infants with EEG-proven convulsions The decision as to which babies to treat with antiepileptic drugs therefore becomes somewhat arbitrary
Do anticonvulsants stop neonatal seizuresAlthough neonatal seizures are common there are few random-ized controlled trials assessing the benefits of antiepileptic drugs (AEDs) in the treatment of this condition Phenobarbitone is the most widely used first-line AED and in an Australasian study 95 of neonatologists and paediatric neurologists used this drug as first-line management12 The most commonly used loading dosage is 20 mgkg but regimens of up to 40 mgkg have been recommended (Table 3)13 Four trials have evaluated the effect of phenobarbitone in abolishing neonatal seizures Two of these studies used EEG to monitor response to the drug1415 and one compared phenobarbitone with phenytoin15 In the latter study seizures were completely controlled in only 43 of babies and in the group where phenytoin was the first drug used com-plete seizure control was achieved in 45 This study switched babies from their first AED to the other if complete control was not obtained on EEG monitoring after exposure to first-line therapy In babies who had been given phenobarbitone as first-line therapy seizure control was only achieved in 57 after phenytoin was added In those given phenytoin first complete
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Dosage regimens for first- second- and third-line anticonvulsants in the neonatal period
Loading dose Second loading dose if first
unsuccessfulMaintenance dose
phenobarbitone 20 mgkg by slow iv injection 10 mgkg iv 25ndash5 mgkg od
phenytoin 20 mgkg iv over 20 min not recommended
midazolam 150ndash200 μgkg iv infusion 1 μgkgmin iv infusion increasing to 5 μgkgmin
until favourable response
lidocaine 2 mgkg iv over 10 min 6 mgkgh for 6 h iv then 4 mgkgh for 12 h then
2 mgkgh for 12 h
lorazepam 005ndash01 mgkg by slow iv injection
Diazepam 03ndash04 mgkg iv over 3ndash5 min
lidocaine should not be used if the infant has previously been treated with phenytoin
Table 3
seizure control was achieved with the adding of phenobarbitone in 62
Boylan et al14 assessed the efficacy of phenobarbitone (20ndash40 mgkg iv over 20 min) in 14 babies monitored by video-EEG in only four was there complete abolition of seizures and in the other 10 electroconvulsive seizure activity increased whereas clinical evidence of seizures reduced This has been termed elec-troclinical dissociation and anticonvulsant drug use in the new-born appears to increase this feature They also showed that the babies least likely to respond to the first-line AED are those with the most abnormal background EEG
Two studies have evaluated the use of phenobarbitone in babies who had sustained significant asphyxial insult at birth Hall et al13 compared high-dose phenobarbitone (mean 39 mgkg) versus standard dose (27 mgkg) and reported fewer convul-sions and a significant reduction of severe disability or death in the high dose group (RR 030 CI 010ndash093) A recent study from India16 of babies with hypoxicndashischaemic encephalopathy ran-domized 25 babies to phenobarbitone (20 mgkg loading dose) and compared them with 20 control babies Only 2 of 25 (4) in the phenobarbitone group developed convulsions compared with 8 of 20 (40) in the control group (p = 001) Because of the specific enrolment criteria (asphyxial insult) neither of these studies is strictly comparable to the studies by Painter et al15 and Boylan et al14 whose intention was to assess the efficacy of first-line anticonvulsant therapy on convulsions of any cause diagnosed either clinically or by EEG
Other anticonvulsants used as second- and third-line drugs have been subject to few studies in the newborn Midazolam is administered as a bolus followed by continuous infusion A recent study17 has shown that in 10 of 13 neonates given intravenous midazolam for status epilepticus control of electri-cal seizures was achieved within the first hour of treatment having been previously shown to be refractory to phenobarbi-tone treatment Some of these babies required a second bolus infusion of midazolam to obtain control of all electrographic seizures
In some parts of Europe lidocaine is used as a third-line anti-convulsant Malingre et al18 evaluated 20 infants refractory to
paeDiatRiCS anD CHilD HealtH 184 180
both phenobarbitone and midazolam and who were then given lidocaine by continuous infusion Lidocaine was effective in abolishing electroconvulsive seizures diagnosed by aEEG in 76 of the treatment courses studied No babies developed cardiac arrhythmias a previously reported complication of lidocaine in older patients As a result of pharmacokinetic studies the dosage regimen has been modified (see Table 3)
In summary phenobarbitone is effective in seizure control in less than 50 of babies and even when combined with phe-nytoin the efficacy of these drugs together remains poor More worrying is the observation that phenobarbitone tends to reduce clinically evident seizures thereby giving the clinician a false sense of security whilst having little or no effect on the num-bers of electroconvulsive disorders This has been summarized appropriately as lsquoafter all these years we still love what doesnrsquot workrsquo19 Both midazolam and lidocaine infusions appear to be effective in abolishing severe seizures in some infants resistant to phenobarbitone Lidocaine should not be given to babies previ-ously exposed to phenytoin for fear of a synergistic adverse effect on cardiac rhythm
Do antiepileptic drugs cause brain damageA riskndashbenefit analysis is needed to evaluate the efficacy of anticonvulsants in stopping neonatal seizures which is poor with standard anticonvulsants as discussed above against the risk of administering the anticonvulsant drugs themselves Phenobarbitone has been reported to have adverse effects on the developing brain including inhibition of brain growth20 neuronal toxicity21 and adverse behavioural and cognitive effects into adult life when administered to young animals22 Phenytoin shows unpredictable plasma levels and potential cardiotoxicity
Recent studies have shown an effect of AED exposure on the developing brain by causing neurodegeneration23 Phenytoin administration to immature rat pups at doses which produce serum levels similar to those achieved in human neonates was associated with widespread neuronal death as a result of apop-tosis (programmed cell death) Phenobarbitone had a similar effect when a dosage regimen similar to 40 mgkg was used and
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
this effect was maximal in the more immature brain Diazepam and clonazepam also resulted in a similar effect Midazolam and lidocaine were not tested in this study The combination of phenobarbitone or phenytoin with diazepam had a particularly profound effect on neurodegeneration
In summary recent data suggest that the commonly used AEDs for neonatal convulsions may in themselves cause neuro-degeneration due to apoptosis with lasting effects on develop-ment Many babies with neonatal convulsions are treated with at least two AEDs and this may produce more severe adverse effects than the seizures themselves
Practical management of neonatal seizures
Assimilation of these data and formulation of a rational policy is difficult when faced with a fitting neonate on an intensive care unit and pressure on the medical staff to lsquodo somethingrsquo but it is important to accept that sometimes doing nothing is preferable to using potentially dangerous drugs in a situation which does not warrant such intervention Many babies who have normal interseizure neurological clinical findings and whose seizures are relatively brief and infrequent probably do not need anticon-vulsant medication A normal or near-normal background EEG trace should reassure the clinician that anticonvulsants can be withheld
Some causes of neonatal convulsions are treatable such as meningitis hypoglycaemia hypocalcaemia and inborn errors of metabolism and each baby should be rapidly and carefully investigated for cause of the convulsions
In some babies clinical assessment of seizures is difficult ie when the baby is very sick small or paralyzed Sometimes it may be difficult to assess the significance of certain movement pat-terns Under these circumstances an EEG may prove to be very helpful In many units EEG is not available out of hours and a simple aEEG or CFM is strongly advised Modern instruments are very simple to apply and prolonged or frequent seizures should be identified with only moderate training The printout can be faxed to a more senior doctor if there is doubt as to what is shown on the trace
The balance of knowledge now is that frequent seizures cause additional damage to the developing brain and that treatment to abolish the seizures is warranted Unfortunately there is little evidence that the majority of seizures can be effectively termi-nated by current standard therapy Furthermore it appears that the more abnormal the background EEG the more difficult it is to control the seizures Nevertheless a written protocol for the management of neonatal convulsions is required on each unit Phenobarbitone and phenytoin remain the mainstay of treat-ment although their effectiveness is disappointing There is little to suggest that midazolam is more effective than lidocaine as third-line therapy but lidocaine is precluded if phenytoin has been previously used
In view of the anxiety as to the neurodegenerative effects on the immature brain of most anticonvulsants used in the neonatal period (particularly when multiple drugs are used) it is prefer-able to use only one drug to maximum dosage before introduc-ing a second In addition the duration of anticonvulsants should be minimized and the drugs stopped at the earliest opportu-nity It is my practice to stop anticonvulsants prior to discharge
paeDiatRiCS anD CHilD HealtH 184 18
from hospital if the baby is neurologically normal on clinical examination
REFEREnCES
1 Ronen gm penney S andrews W the epidemiology of clinical
neonatal seizures in newfoundland a population-based study
J Pediatr 1999 134 71ndash75
2 lanska mJ lanska DJ Baumann RJ et al a population-based study
of neonatal seizures in Fayette County Kentucky Neurology 1995
45 724ndash732
3 Rennie Jm Chorley g Boylan gB et al non-expert use of the
cerebral function monitor for neonatal seizure detection Arch Dis
Child Fetal Neonatal Ed 2004 89 F37ndashF40
4 tekgul H gauvreau K Soul J et al the current etoliologic profile
and neurodevelopmental outcome of seizures in term newborn
infants Pediatrics 2006 117 1270ndash1280
5 Surtees R Wolf n treatable neonatal epilepsy Arch Dis Child 2007
92 659ndash661
6 Ben-ari y Holmes gl effects of seizures on developmental
processes in the immature brain Lancet Neurol 2006 5 1055ndash
1063
7 Holmes gl gairsa Jl Chevassus-au-louis n et al Consequences of
neonatal seizures in the rat morphological and behavioral effects
Ann Neurol 1998 44 845ndash857
8 Stafstrom Ce Chronopoulos a thurber S et al age-dependent
cognitive and behavioural deficits following kainic-acid inducing
seizures Epilepsia 1993 34 420ndash432
9 Schmid R tandon p Stafstrom Ce et al effects of neonatal seizures
on subsequent seizure-induced brain injury Neurology 1999 53
1754ndash1761
10 Hoffmann aF Zhao Q Holmes gl Cognitive impairment following
status epilepticus and recurrent seizures during early development
support for the ldquotwo-hit hypothesisrdquo Epilepsy Behav 2004 5
873ndash877
11 Wirrell eC armstrong ea osman lD et al prolonged seizures
exacerbate perinatal hypoxic-ischemic brain damage Pediatr Res
2001 50 445ndash454
12 Carmo KB Barr p Drug treatment of neonatal seizures by
neonatologists and paediatric neurologists J Paediatr Child Health
2005 41 313ndash316
13 Hall Rt Hall FK Daily DK High-dose phenobarbital therapy in term
newborn infants with severe perinatal asphyxia a randomized
prospective study with three-year follow-up J Pediatr 1998 132
345ndash348
14 Boylan gB Rennie Jm pressler Rm et al phenobarbitone neonatal
seizures and video-eeg Arch Dis Child Fetal Neonatal Ed 2002 86
F165ndash170
15 painter mJ Scher mS Stein aD et al phenobarbital compared with
phenytoin for the treatment of neonatal seizures N Engl J Med
1999 341 485ndash489
16 Singh D Kumar p narang a a randomized controlled trial of
phenobarbital in neonates with hypoxic ischemic encephalopathy
J Matern Fetal Neonatal Med 2005 18 391ndash395
17 Castro Conde JR Borges H Domenech martinez e et al midazolam
in neonatal seizures with no response to phenobarbital Neurology
2005 64 876ndash879
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
18 malingre mm Van Rooij lgm Rademaker Cma et al Development
of an optimal lidocaine infusion strategy for neonatal seizures Eur
J Pediatr 2006 165 598ndash604
19 Sankar R painter mJ neonatal seizures after all these years we still
love what doesnrsquot work Neurology 2005 64 776ndash777
20 Diaz J Schain J Bailey Bg phenobarbital-induced brain growth
retardation in artificially reared rat pups Biol Neonate 1977 32 77ndash82
21 mattson RH phenobarbital toxicity in levy RH Dreifuss Fe
mattson RH et al eds antiepipeptic Drugs 3rd edn new york
Raven 1985 p 341ndash355
22 mikati ma Holmes gl Chronopoulos a et al phenobarbital
modifies seizure-related brain injury in the developing brain Ann
Neurol 1994 36 425ndash453
23 Bittigau p Sifringer m genz K et al antiepileptic drugs and
apoptotic neurodegeneration in the developing brain Proc Natl
Acad Sci U S A 2002 99 15089ndash15094
paeDiatRiCS anD CHilD HealtH 184 182
Practice points
bull the clinician needs to be aware that almost any repetitive
stereotype movement pattern can be a manifestation of
neonatal seizures
bull eeg is important in defining neonatal seizures
bull Frequent short-lived seizures have been shown to cause long-
term neurodevelopmental problems
bull Conventional anticonvulsant medication is ineffective in
abolishing neonatal seizures in greater than 50 of cases
bull there is evidence that exposure of the neonatal brain to
multiple anticonvulsants causes neuronal death
bull Future research is needed to evaluate more effective
anticonvulsants for treating this condition
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
Emotional support for families of sick neonatesMarina nicolaou
cristine Glazebrook
AbstractParents of sick neonates experience high levels of stress anxiety and
depression Most interventions with families of sick infants have focused
on fostering the motherndashinfant relationship through the provision of
information about infant developmental needs or through increased
motherndashinfant contact Many of these studies have reported improved
maternal well-being though there are some concerns about the scope
and practicality of large-scale interventions The few studies to have
prioritized emotional support for parents of sick neonates have pro-
duced encouraging results even interventions requiring relatively few re-
sources such as telephone support parent-to-parent support and group
support have been associated with reduced psychological morbidity for
parents The needs of parents can change throughout their infantrsquos hos-
pitalization and not all want or benefit from the provision of additional
support Thus neonatal intensive care units should aim to provide a
varied flexible and sustainable programme of support options Further
research should focus on the needs of fathers
Keywords mental health neonatal intensive care parents
The admission of an infant to neonatal care is acknowledged to be a source of considerable distress for families This review aims to explore evidence for the psychological impact on families of having an infant in neonatal intensive care and to identify evi-dence for the effectiveness of interventions to promote parental well-being It will conclude with recommendations for strategies to support parents of vulnerable infants and suggestions for fur-ther research
Psychological impact of neonatal care for parents
The majority of research examining the effect on parents of having a sick neonate has focused on families of premature or low birthweight infants Such research has found that parents with a sick neonate exhibit high levels of stress compared to normative samples and to parents of healthy full-term infants1 Singer et al2 examined the stress experienced by mothers of high-risk very low birthweight (VLBW) low-risk VLBW and term
Marina Nicolaou MPhil is a Teaching Assistant at the School of
Community Health Sciences University of Nottingham Nottingham UK
Cristine Glazebrook PhD is a Professor of Health Psychology at the School
of Community Health Sciences University of Nottingham Nottingham UK
PaeDiaTrics anD cHilD HealTH 184 196
infants Several self-report measures were used including the Brief Symptom Inventory the Parenting Stress Index (PSI) the Impact on Family Scale and the Family Inventory of Life Events and Changes (FILE) Mothers of VLBW infants had more psycho-logical distress at 1 month compared to mothers of term infants Mothers of high-risk VLBW infants also reported high psycho-logical distress at 2 years and high levels of parenting stress at 3 years Mothers have also been found to have higher stress levels compared to fathers Shaw et al3 examined the prevalence of acute stress disorder (ASD) in 40 parents whose infants were in the neonatal intensive care unit (NICU) Nearly half of the moth-ers (44) met the criteria for ASD although none of the fathers did Furthermore the severity of the symptoms (measured by the number of concurrent symptoms) was greater for the moth-ers than for the fathers3 The reasons behind this difference have been widely speculated with some believing that it is due to the mothersrsquo greater psychological involvement with the infant as evidenced by their general greater vulnerability to postpartum psychological disorder It could also reflect gender differences in coping style
Having an infant who requires intensive medical care repre-sents a significant emotional burden for families Not only is there extreme anxiety surrounding the infantrsquos health and distress for the childrsquos suffering there is also the unfamiliar and intimidating environment of the NICU to adjust to Hopper in her review of the literature identified sources of stress for parents of sick neo-nates as falling into three areas4 Situational factors included the severity of the infantrsquos illness and how parents adapted to the life crisis of having a sick infant Personal factors involved parental emotions about their roles and the instrumental and informa-tional support which were available to them The third area was classified as environmental sources of stress and included the environment of the NICU and the relationship between parents and members of staff This relationship has been examined by several studies in the nursing literature nurses are seen as ide-ally placed to provide the necessary support and information to parents with sick neonates However whilst some studies have shown that supportive and helpful hospital staff can have a posi-tive effect on parents other studies have highlighted the prob-lems and difficulties which can manifest It has been shown that parents and nurses often have very different ideas about issues eg the necessary skills and competencies needed in an NICU or the characteristics that make a lsquogood motherrsquo
Research has shown that there may be a relationship between high levels of parental stress and an increased likelihood of depression5 Postpartum depression is a psychiatric illness which appears in 10ndash15 of postpartum women Its reported preva-lence rates however have ranged from less than 10 up to 306 depending on the instruments used the population exam-ined and the timing of the research Several factors have been found to be associated with postpartum depression including poor social support and infant-related stressors6 Evidence indi-cates that postnatal depression may be underreported and this is of concern since the mental and psychological health of the mother can affect her relationship with her infant and thus the infantrsquos cognitive and emotional development5 Depressed moth-ers appear to look touch and talk to their infants less frequently and also appear to show fewer positive and more negative faces7 The vocalizations of mothers suffering with depression have also
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
been found to be less effective at promoting cognitive growth and learning in infants8
If researchers are interested in finding ways of providing sup-port for families of sick neonates then they must listen to what such families perceive their needs to be in order to avoid increas-ing anxiety and distress Furthermore the provision of appropri-ate support be it emotional informational or social will enhance parental coping abilities increase self-esteem and reduce anxiety It should be noted though that the research conducted around these issues has often taken lsquosupport needsrsquo as being synony-mous with lsquoinformation needsrsquo Such studies have examined the type the amount and quality of information that parents receive and perceive themselves as needing but have not explored in equal depth the perceived emotional support needs of families who have a sick infant In addition the needs of parents may change throughout their infantrsquos illness Ward examined the per-ceived needs of 52 parents of infants in an NICU9 Parents rated the needs of their hospitalized infant as most important along with the need to be reassured Interestingly they ranked their support needs as least important This research was conducted during the first week of the infantsrsquo hospitalization however which would explain the preoccupation of the parents with the infantrsquos health These results demonstrate that if researchers want to find ways of providing emotional support to parents of sick neonates they must be prepared not only to listen to parents but also to be flexible enough to satisfy the parentsrsquo changing needs and expectations
Interventions aimed at supporting parents
Most interventions that been evaluated in controlled studies have focused on supporting the motherndashinfant relationship and provid-ing information on infant development Many of these interven-tions have included the aim of improving the parental emotional state and thus psychological outcomes such as stress or anxi-ety have been assessed However few studies appear to include fathers This means that strategies implemented to provide emo-tional support to families of sick neonates are often derived from interventions tailored for mothers even though fathers may have different emotional needs
A wide range of interventions with mothers and infants has been evaluated in the NICU Increasing motherndashinfant contact through kangaroo care has been found to reduce maternal anxiety1011 and educational programmes delivered to fami-lies in the NICU have also been associated with reduced emo-tional difficulties in parents12ndash14 Kaaresen and colleagues implemented an intervention which consisted of eight sessions before discharge and four home visits all by trained nurses The sample included 71 premature infants in the intervention group 69 premature infants in the control group and 74 infants in the full-term control group The randomized controlled trial found that the intervention reduced parenting stress in both mothers and fathers of premature infants compared to controls to a level equivalent to parents in the term control group13 At 6 months corrected age mothers of preterm infants who had not received the intervention had total PSI scores which were 17 points higher than the mothers of infants born at term (an effect size of 057) A similar study evaluated the efficacy of an educationalndashbehavioural programmendashCreating Opportunities for
PaeDiaTrics anD cHilD HealTH 184 19
Parent Empowerment (COPE) ndash through a randomized controlled trial with 260 families of premature infants14 COPE was a four-phase educationalndashbehavioural programme which began as early as 2ndash4 d after mothers had given birth and continued until 1 week after discharge from the NICU The programme consisted of audiotaped and written infant behaviour information along with photographs which focused on common behaviours and characteristics of premature infants It also included various par-ent activities in the form of a four-phase workbook which aimed to assist mothers in the implementation of the experimental infor-mation COPE was found significantly to reduce maternal stress in the NICU as well as maternal anxiety and depressive symptoms after hospitalization In contrast a cluster randomized trial of a parenting intervention delivered to mothers of very premature infants from soon after birth showed no benefits for parenting stress1 The authors hypothesized that the intervention had not been of sufficient intensity particularly in the weeks surrounding discharge Neonatal care presents a significant barrier to parent-ing in the early weeks following a very preterm birth and so inter-ventions which focus on the developmental needs of infants and the parentndashchild relationship should particularly aim to support parents as they take on the parenting role There was also concern that the intervention had failed to reach those most at risk
Since large-scale projects can be costly to implement and may often fail to reach the families in most need it may be wiser to focus on intervention programmes which are more practical and easier to implement within a neonatal care setting Research has shown that even interventions which are based on one-off meet-ings with parents of sick neonates can be effective Jotzo and Poets examined the effect of an intervention programme aimed at reducing the severity of traumatic responses as a result of giv-ing birth prematurely15 Their programme consisted of a one-off intervention meeting along with additional psychological help throughout the hospitalization of the infant The meeting cov-ered a variety of issues including a reconstruction of the events shortly before and after the infantrsquos birth relaxation techniques discussion of coping strategies available resources and social support and support during emotional outbursts The measures used included the Impact of Event Scale (IES) and the Peritrau-matic Dissociative Experience Questionnaire At discharge the mothers who received the intervention were found to have a significantly lower traumatic impact as a result of premature birth Furthermore fewer mothers in the intervention group showed symptoms of clinically significant psychological trauma at discharge compared to mothers in the control group (36 vs 76)15 The lsquoParents Circle Programrsquo is another intervention with a similar structure16 This consisted of a 90 min session for parents with the aim of enhancing the developing relationship between parents and infants and to offer parents support A total of 104 parents (59 mothers and 45 fathers) and 44 members of hospital staff were asked to evaluate the programme and their results were analysed using content analysis Families reported gaining perspective on their situation feeling supported becom-ing aware of cues and optimizing interactions and becoming aware of available resources Parents and staff alike felt that participating in the intervention helped parents overcome the difficulties associated with the early time of their infantrsquos hos-pitalization Additional studies have also found positive results with fairly minimal interventions including discussion groups
7 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
in the NICU music during kangaroo care and pairing mothers of sick neonates with trained mothers who had been through similar experiences
Parent support programmes
Parent support programmes (PSPs) which are based in NICUs can provide parents with the opportunity to talk to parents who have been in similar situations and also to discuss their emo-tions with professionals who can help them cope with their situa-tion111718 The parent-to-parent support programme for mothers of preterm infants evaluated by Preyde and Ardal included edu-cational parental support group meetings and individual par-ent-to-parent support (primarily telephone support)19 Measures used included the Parental Stressor Scale NICU the State and the Trait Anxiety Inventories and the Beck Depression Inven-tory After 4 months of participation mothers in the intervention group reported lower levels of stress state anxiety and depres-sion compared to control group mothers The authors speculated however that the participants who were able to meet face to face with other parents were those who benefited the most Hurst conducted a comprehensive survey of an NICU-based PSP This PSP was provided in a variety of formats including a weekly parent support group hospital visitation and 24-h telephone sup-port20 Of the 477 participants 303 families used the PSP dur-ing a 2-year evaluation period with 78 using only one form of support and 18 using two forms Of a sub-sample of 48 parents asked to complete an evaluation of the PSP 92 stated that they would recommend such a programme to other parents Furthermore the majority of parents felt that it made them feel supported and helped them deal with their emotions20 This is an indication that such programmes can be very successful in sup-porting parents throughout their infantrsquos hospitalization It also shows that it can be beneficial to give parents several options and formats when it comes to such support services It is impor-tant to consider though that both the Hurst and the Preyde and Ardal studies found that some participants did not find the sup-port programmes helpful even reporting that they had caused them increased stress and anxiety Therefore it should not be assumed that support programmes will suit every individual and will provide the required support for all parents1920 NICUs need to be flexible enough to provide parents with a range of forms of support to choose from
The increased understanding of the strains that parents of sick neonates have to deal with has also led to efforts to improve customary practices in NICUs Family-centred care focuses on infants and their needs and attempts to redefine the relationship between parents and caregivers These practices strive to provide parents with support during their infantrsquos illness by focusing on freely sharing information and on the collaboration between parents and hospital staff Family-centred care has been found to be associated with several beneficial outcomes including improved parental satisfaction increased parental comfort staff satisfaction and decreased parental stress18 Research is already examining these practices and questioning how these can be improved further Such research reflects the increasing effort focused on lsquohumanizingrsquo the environment in NICUs in order to make parents feel more comfortable about spending time with their infants
PaeDiaTrics anD cHilD HealTH 184 19
Conclusion
Surprisingly few interventions have prioritized the provision of emotional support for parents of sick neonates or accounted for the changing needs and wishes of parents over the course of their infantrsquos care Large-scale supportive education-based inter-ventions have been shown to be effective in reducing parental distress However the feasibility and sustainability of such pro-grammes should also be considered Programmes which require significant additional resources can be expensive and there are also issues of training and quality control Interventions which require significant input from parents may also place additional burdens on families making them potentially less accessible to those most at risk Arguably the aim should be to explore ways of providing acceptable and effective informational support which could be complemented by emotional support from health professionals and from other parents in the unit Increasingly studies are exploring the use of computers and multimedia as an engaging flexible and cost-effective method of targeting indi-vidual needs and providing support and information Such com-puter-based and interactive multimedia interventions have been found to be successful with a range of patient groups and could therefore be examined as a complementary method of providing informational support to families with sick neonates
REfEREnCEs
1 Glazebrook c Marlow n israel c et al randomised trial of a
parenting intervention during neonatal intensive care Arch Dis Child
Fetal Neonatal Ed 2007 92 F438ndash443
2 singer lT salvator a Guo s collin M lilien l Baley J Maternal
psychological distress and parenting stress after the birth of a very
low-birth-weight infant JAMA 1999 281 799ndash805
3 shaw rJ Deblois T ikuta l Ginzburg K Fleisher B Koopman c
acute stress disorder among parents of infants in the neonatal
intensive care nursery Psychosomatics 2006 47 206ndash212
4 Hopper a sources of stress for parents of a sick neonate a
literature review Pediatr Nurs 2000 30 29ndash32
5 Davis l edwards H Mohay H wollin J The impact of very
premature birth on the psychological health of mothers Early Hum
Dev 2003 73 61ndash70
6 Bernazzani O saucier J-F David H Borgeat F Psychosocial
predictors of depressive symptomatology level in postpartum
women J Affect Disord 1997 46 39ndash49
7 Field T infants of depressed mothers Infant Behav Dev 1995 18
1ndash13
8 Kaplan Ps Bachorowski J-a Zarlengo-strouse P child-directed
speech produced by mothers with symptoms of depression fails
to promote associative learning in 4-month-old infants Child Dev
1999 70 560ndash570
9 ward K Perceived needs of parents of critically ill infants in
a neonatal intensive care unit (nicU) Pediatr Nurs 2001 27
281ndash286
10 lai Hl chen cJ Peng Tc et al randomized controlled trial of music
during kangaroo care on maternal state anxiety and preterm infantsrsquo
responses Int J Nurs Stud 2006 43 139ndash146
8 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
11 Tallandini Ma scalembra c Kangaroo mother care and mother-
premature infant dyadic interaction Infant Ment Health J 2006 27
251ndash275
12 Ohgi s Fukuda M akiyama T Gima H effect of an early intervention
programme on low birthweight infants with cerebral injuries
J Paediatr Child Health 2004 40 689ndash695
13 Kaaresen Pi ronning Ja Ulvund se Dahl lB a randomized
controlled trial of the effectiveness of an early-intervention program
in reducing parenting stress after preterm birth Pediatrics 2006
118 e9ndash19
14 Melnyk BM Feinstein nF alpert-Gillis l et al reducing premature
infantsrsquo length of stay and improving parentsrsquo mental health
outcomes with the creating opportunities for parent empowerment
(cOPe) neonatal intensive care unit program a randomized
controlled trial Pediatrics 2006 118 e1414ndash1427
15 Jotzo M Poets cF Helping parents cope with the trauma of
premature birth an evaluation of a trauma-preventive psychological
intervention Pediatrics 2005 115 915ndash919
16 Pearson J andersen K evaluation of a program to promote positive
parenting in the neonatal intensive care unit Neonatal Netw 2001
20 43ndash48
17 roman l lindsay J Boger r et al Parent-to-parent support
initiated in the neonatal intensive care unit Res Nurs Health 1995
18 385ndash394
18 Meyer ec coll cTG lester BM Boukydis cFZ McDonough sM Oh w
Family-based intervention improves maternal psychological well-
being and feeding interaction of preterm infants Pediatrics 1994
93 241ndash246
PaeDiaTrics anD cHilD HealTH 184 19
19 Preyde M ardal F effectiveness of a parent ldquobuddyrdquo program for
mothers of very preterm infants in a neonatal intensive care unit
CMAJ 2003 168 969ndash973
20 Hurst i One size does not fit all Parentsrsquo evaluations of a support
program in a newborn intensive care nursery J Perinat Neonatal
Nurs 2006 20 252ndash261
Practice points
bull Parents of sick neonates experience significant distress and
exhibit higher levels of stress anxiety and depression than
parents of healthy infants
bull educational support emotional support and increased
motherndashinfant contact have been shown to promote maternal
well-being
bull emotional support for fathers has been largely neglected in
the research literature
bull Parents benefit from a choice of supportive facilities which
could include face-to-face sessions with health professionals
telephone support hospital visitation parent-to-parent
support and unit-based group support meetings
bull Parentsrsquo support needs can change during their infantrsquos
hospitalization and not all parents want or benefit from the
provision of additional information and emotional support in
the neonatal unit
9 copy 2008 elsevier ltd all rights reserved
Personal Practice
When should enteral feeds be started in preterm infantsnicholas D embleton
AbstractPaediatricians are regularly faced with the question of when best to start
enteral feeds in preterm infants this is important as longer term out-
come may be compromised by sub-optimal nutrition in early life clinical
factors that may affect the decision to start and the risk and benefits
are discussed
Keywords breast milk feeding nutrition parenteral nutrition
Key points in the history
Alice is lsquonutritionally vulnerablersquo and whilst this may not be immediately apparent it will affect her long term outcome Her energy stores are extremely limited and consist primarily of pro-tein She has less than 5 fat and little energy associated with stored glycogen She is losing about 1 gkgd protein equivalent so she needs at least that and a minimum of 50ndash60 kcalkg of energy just to maintain the status quo let alone grow
Her weight is on the 25th centile Review of any antenatal his-tory may reveal whether fetal growth was normal Fetal growth retardation can occur with a weight greater than 10th centile The presence of antenatal absent or reversed end diastolic flow in the umbilical artery indicates poor gut blood flow This increases the risk of necrotizing enterocolitis (NEC) and might suggest a more cautious approach to starting feeds1
She has no important cardiovascular problems but if she were hypotensive gut blood flow may be low There is no umbilical
Nicholas D Embleton BSC (Hons) MBBS (Hons) MD FRCPCH is Consultant in
Neonatal Medicine at Newcastle Neonatal Service Royal Victoria
Infirmary Newcastle upon Tyne NE1 4LP UK
Should you start feeds at a day of age
alice was born following spontaneous labour at 30 weeksrsquo
gestation she weighed 1300 g and is now 18 h old she was
briefly ventilated and then extubated to continuous positive
airway pressure 12 h ago in 35 oxygen she has had caffeine
citrate but still has intermittent episodes of self-correcting
apnoea she was commenced on iv 10 dextrose but this was
replaced by a parenteral amino acid solution (referred to as
lsquotPnrsquo) along with intralipid at 0900 this morning serum glucose
is 11 mmoll and blood pressure is 42 systolic
PaeDiatrics anD cHilD HealtH 184 20
arterial catheter in situ but there is no good evidence that this should delay the decision to start feeds Her glucose is high but this is quite common in a baby like this Could this be a sign of sepsis Caffeine does not affect the incidence of NEC2 The great-est risk factor for NEC in this case is prematurity
What else might be found on examination
Up until 24 h ago she was swallowing large amounts of amniotic fluid What will have changed since then
General examination should confirm peripheral perfusion lsquogestaltrsquo view (does she look lsquowellrsquo) and cardiovascular status lsquoBowel soundsrsquo are not usually helpful
The most important variable likely to affect gut perfusion is the arterial duct Precordial lsquoheaversquo and a loud murmur are sug-gestive but it is possible to have a significant ductal shunt in a baby with a normal examination Cardiac ultrasound will con-firm this diagnosis It might be better to treat a large shunt first with indometacin and to delay starting feeds for a further 24 h
It is not possible to assess gut perfusion clinically but normal perfusion elsewhere (adequate urine output usually indicates adequate renal perfusion) would be reassuring Most preterm babies have a few abdominal lsquoloopsrsquo visible but a distended abdomen with many palpable loops suggests ileus This might be secondary to sepsis or poor gut blood flow Preterm babies do not pass much meconium in the first 24ndash48 h
Balance of risks between starting and withholding feeds
Alice requires 35ndash4 gkgd of protein and 120 kcalkgd to grow3 This will initially be provided parenterally Delaying feeds increases the risk of gut villous atrophy and prolongs the need for lsquototal parenteral nutrition (TPN)rsquo TPN requires intravenous access and so increases the risk of sepsis and when prolonged use is required combined with the lack of enteral feeding may result in hepatic impairment
Delaying feeds may allow a gut that has been chronically under-perfused to re-establish more normal perfusion although normal gut endocrine function digestive enzyme upregulation and motility require a source of intraluminal nutrients1 A recent study suggested benefit from delaying the introduction of feeds4 but methodologi-cal problems exist5 Although a Cochrane meta-analysis suggested no benefit only two studies were included6 A large UK-based trial is examining the effect of early or late feeding in preterm infants who were born growth retarded following identification of antena-tal absent or reversed end diastolic flow in the umbilical artery7
When starting feeds what volume should be used
There are no good data to guide this decision We start with 24 mlkg (1 mlkgh) and then increase by this amount each day Most babies achieve full enteral feeds (ge150 mlkgd) by a week of age Feeding guidelines improve the outcome8 Measure-ment or assessment of gastric aspirates is not consistently useful in predicting subsequent feeding intolerance or development of NEC Aspirate volumes equivalent to or sometimes greater than the amount given in the preceding 1ndash2 h are usually normal Most aspirates have a greenish colour Thick bloody or intensely bile-stained aspirates require detailed assessment
0 copy 2008 elsevier ltd all rights reserved
Personal Practice
What else affects decisions and outcome
Feeding success is affected by sepsis and NEC Scrupulous atten-tion should be paid to hand washing and intravenous access and blood sampling should be minimized There is no good evidence to support the routine use of pro-kinetic agents or H2 blockers
The most important clinical intervention affecting the occur-rence of NEC is the use of breast milk9 All efforts should be directed at persuading parents of the benefits and supporting the process Some clinicians delay starting feeds for a further 24 h whilst expressed breast milk becomes available Donor breast milk might be equally efficacious10
RefeRenceS
1 Dorling J Kempley s leaf a Feeding growth restricted preterm
infants with abnormal antenatal Doppler results Arch Dis Child Fetal
Neonatal Ed 2005 90 F359ndash363
2 schmidt B roberts rs Davis P et al caffeine therapy for apnea of
prematurity N Engl J Med 2006 354 2112ndash2121
PaeDiatrics anD cHilD HealtH 184 20
3 embleton nD Pang n cooke rJ Postnatal malnutrition and growth
retardation an inevitable consequence of current recommendations
in preterm infants Pediatrics 2001 107 270ndash273
4 Berseth cl Bisquera Ja Paje VU Prolonging small feeding volumes
early in life decreases the incidence of necrotizing enterocolitis in
very low birth weight infants Pediatrics 2003 111 529ndash534
5 Menon G Boyle eM embleton nD et al introduction of enteral
feeds in preterm infants Pediatrics 2004 114 327ndash328
6 Kennedy Ka tyson Je chamnanvanikij s early versus delayed
initiation of progressive enteral feedings for parenterally fed low
birth weight or preterm infants Cochrane Database Syst Rev 2000
cD001970
7 wwwnpeuoxacukadept
8 Patole sK de Klerk n impact of standardised feeding regimens on
incidence of neonatal necrotising enterocolitis a systematic review
and meta-analysis of observational studies Arch Dis Child Fetal
Neonatal Ed 2005 90 F147ndash151
9 lucas a cole tJ Breast milk and neonatal necrotising enterocolitis
Lancet 1990 336 1519ndash1523
10 Boyd ca Quigley Ma Brocklehurst P Donor breast milk versus
infant formula for preterm infants systematic review and meta-
analysis Arch Dis Child Fetal Neonatal Ed 2007 92 F169ndash175
1 copy 2008 elsevier ltd all rights reserved
self-assessment
Case 1A term male infant born to consanguineous parents is assessed at 24 h of age due to poor feeding profuse yellow watery diar-rhoea and irritability He weighed 32 kg at birth and delivery was uneventful There was no polyhydramnios He has been breastfed since birth On examination he is pale with a non-tender but distended abdomen and reduced bowel sounds His weight is 275 kg and he looks dehydrated Examination is otherwise normal
Initial investigations (normal values in parentheses) showed
sodium 149 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 65 mmollitre (25ndash75)
creatinine 147 μmollitre (40ndash110)
chloride 119 mmollitre (95ndash105)
haemoglobin 172 gdl (140ndash200)
White blood cell count 80 times 109litre (100ndash260)
Platelet count 302 times 109litre (150ndash400)
arterial blood gas
ph 720 (730ndash745)
PcO2 23 kPa (46ndash60)
Bicarbonate 68 mmollitre (220ndash260)
Base excess minus186 mmollitre (minus20 to +20)
lactate 59 mmollitre (06ndash24)
An abdominal X-ray shows distended bowel loops with no intramural thickening or pneumoperitoneum (Figure 1)
He was given nil by mouth and received intravenous fluids and antibiotics His dehydration improved but the metabolic acidosis and diarrhoea persisted despite receiving no enteral feeds and the commencement of total parenteral nutrition Blood and stool cultures were negative
1 Which of the following best describes these results Choose ONE answer ONLY from the followingA Hypernatraemia hyperchloraemic metabolic acidosis
with increased anion gapB Hypernatraemia hyperchloraemic metabolic acidosis
with normal anion gap
Manish Sadarangani BM BCh MA MRCPCH is Clinical Research Fellow
at the Department of Paediatrics University of Oxford Centre for
Clinical Vaccinology and Tropical Medicine Churchill Hospital
Oxford OX3 7LJ UK
Shabna Rajapaksa MB BChir MA MRCPCH is Specialist Registrar in
Paediatrics at the Paediatric Intensive Care Unit John Radcliffe
Hospital Oxford OX3 9DU UK
Nicholas Mann MD FRCP FRCPCH DCH is Consultant Paediatrician at the
Department of Paediatrics Royal Berkshire Hospital Reading RG1
5AN UK
self-assessment
C Hypernatraemic dehydration and compensated metabolic acidosis
D Acute renal failureE Renal tubular acidosis
2 What is the likely diagnosis Choose ONE answer ONLY from the followingA Hirschsprung disease ndash long segmentB Cystic fibrosis with meconium ileusC Microvillus inclusion diseaseD Cowrsquos milk protein intoleranceE Lactose intolerance
3 What is the investigation of choice Choose ONE answer ONLY from the followingA Rectal biopsy with staining for acetylcholine receptorsB Immunoreactive trypsinC Gastrointestinal endoscopy and biopsyD Stool microscopy and cultureE Stool reducing substances
Case 2A 4-year-old boy presents with a 3 d history of jaundice and a florid rash He has had orange urine and there is no change in his stool colour His family originate from Kosovo and have lived in the UK for the last 8 years He has never left the UK There is no history of blood transfusion or sex-ual abuse The grandmother was recently diagnosed with hepatitis B
On examination he is well apyrexial and mildly jaundiced with cervical and axillary lymphadenopathy He has an exten-sive papular rash over the face extremities and trunk (Figure 2) There is 3 cm hepatomegaly with no splenomegaly or ascites Examination is otherwise normal
Figure 1 abdominal X-ray of baby
Paediatrics and child health 184 202 copy 2008 elsevier ltd all rights reserved
self-assessment
Initial investigations are as follows
haemoglobin 110 gdl (113ndash135)
White blood cell count 108 times 109litre (50ndash150)
Platelet count 278 times 109litre (150ndash400)
inr 10 (08ndash12)
aPt ratio 10 (08ndash13)
sodium 140 mmollitre (135ndash145)
Potassium 42 mmollitre (35ndash50)
Urea 56 mmollitre (25ndash75)
creatinine 65 μmollitre (45ndash120)
total bilirubin 66 μmollitre (0ndash15)
conjugated bilirubin 23 μmollitre (0ndash10)
alanine aminotransferase (alt) 2033 iUlitre (0ndash35)
alkaline phosphatase 987 iUlitre (71ndash234)
Gamma-glutamyl transferase (GGt) 870 iUlitre (0ndash51)
1 What is the name of this rash Choose ONE answer ONLY from the followingA Erythema multiformeB Erythema migransC GianottiminusCrosti syndromeD EczemaE Dermatitis herpetiformis
2 What is the most likely diagnosis Choose ONE Answer ONLY from the followingA Autoimmune hepatitisB Hepatitis BC Hepatitis DD Wilson diseaseE Alpha-1 antitrypsin deficiency
3 What is the best means of management Choose ONE answer ONLY from the followingA Isolation until the jaundice disappearsB ImmunosuppressionC Copper chelating agents and genetic counsellingD Patient and family education with consideration of
antiviral agentsE Liver transplantation
Case 3A 10-month-old boy presents with 3 weeks of vomiting and constipation ndash he is passing hard stools every 2ndash3 days He has fallen from the 9th to below the 04th centile in the last 6 weeks He passed meconium within the first 24 h of life On examina-tion he looks pale and there are some dysmorphic features ndash a short nose long philtrum and wide mouth He has normal heart sounds with a grade 3 ejection systolic murmur loudest at the upper right sternal edge Examination is otherwise normal
Initial investigations are as follows
haemoglobin 91 gdl (113ndash141)
total white blood cell count 124 times 109litre (60ndash170)
Platelet count 407 times 109litre (150ndash400)
sodium 144 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 78 mmollitre (25ndash75)
creatinine 78 μmollitre (45ndash120)
albumin 52 glitre (35ndash50)
corrected calcium 384 mmollitre (238ndash263)
Phosphate 167 mmollitre (099ndash157)
1 What is the most likely diagnosis Choose ONE answer ONLY from the followingA HyperparathyroidismB Acute leukaemiaC Williams syndromeD Hypervitaminosis DE Familial hypocalciuric hypercalcaemia
2 Which investigation would be most useful in establishing the diagnosis Choose ONE answer ONLY from the followingA Intact parathyroid hormone assayB Blood filmC Fluorescent in-situ hybridization for 7q1123 deletionD 25-hydroxyvitamin D assayE Urine calciumcreatinine ratio
3 Which of the following treatments would not be suitable for this patient Choose ONE answer ONLY from the followingA Low calcium dietB Normal saline infusionC FurosemideD CorticosteroidsE Bisphosphonates
Case 4A 10-week-old girl presents with a 2-day history of poor feed-ing Her mother has been concerned about weakness since birth She only has a flicker of movement in the arms none in the legs and has a weak cry She has been passing urine and opening her bowels normally She was born at full term by normal delivery and did not require any resuscitation at birth Normal fetal movements were felt antenatally and there was no polyhydramnios She is the first child of non- consanguineous parents and there is no significant family his-tory On examination she is alert and fixing and following appropriately She has a weak cry and a weak suck There is reduced central and peripheral tone with marked head lag
Figure 2 rash found on examination
Paediatrics and child health 184 203 copy 2008 elsevier ltd all rights reserved
self-assessment
Muscle power is grade 3 out of 5 in the arms and legs There is no muscle or tongue fasciculation and she has absent reflexes throughout The remainder of the examination is normal
Electromyogram shows irregular polyphasic motor unit potentials with marked instability consistent with a dener-vating and re-innervating process (Figure 3)
1 Which of the following additional investigations may be helpful Choose ONE answer ONLY from the followingA Nerve conduction studiesB Creatine kinase assayC Muscle biopsyD SMN1 gene analysisE All of the above
2 What is the most likely cause of this childrsquos symptoms Choose ONE answer ONLY from the followingA Congenital myotonic dystrophyB Duchenne muscular dystrophyC PraderminusWilli syndromeD Spinal muscular atrophyE Mitochondrial myopathy
3 What is the mode of inheritance of this disease Choose ONE answer ONLY from the followingA X-linked recessiveB Autosomal recessiveC Autosomal dominantD MitochondrialE Sporadic
Case 5A 13-year-old girl presents with a 3-week history of fever up to 40degC night sweats and headache She has a reduced appetite with some weight loss She has no other specific symptoms She was on holiday in China 7 months ago On examination she looks well and has a temperature of 387degC There is no lymphadenopathy and no rashes Examination is entirely normal
Results of investigations are as follows
haemoglobin 126 gdl (120ndash160)
total white blood cell count 132 times 109litre (43ndash108)
neutrophil count 115 times 109litre (25ndash75)
Platelet count 244 times 109litre (150ndash400)
Blood film neutrophilia with left shift
erythrocyte sedimentation rate 63 mmh (1ndash20)
c-reactive protein 219 mglitre (0ndash5)
Blood culture Streptococcus intermedius
from anaerobic bottle only
csf culture negative
Magnetic resonance imaging (MRI) of the brain shows acute frontal sinusitis with a large intracranial frontal extra-dural empyema (Figure 4)
1 Which of the following would be appropriate management Choose ONE answer ONLY from the followingA A 12-week course of intravenous antibioticsB Drainage of the frontal sinus followed by 2 weeks of
intravenous antibioticsC Drainage of the empyema followed by 2 weeks of
intravenous antibioticsD Drainage of the empyema and the frontal sinus
followed by 2 weeks of oral antibiotics
1151
1152
1153
1154
1155
1156
1157
1158
1159
1200
50ms 1mV
Figure 3 electromyogram recording from the patient Figure 4 Parasagittal section from mri scan of patient
Paediatrics and child health 184 204 copy 2008 elsevier ltd all rights reserved
self-assessment
E Drainage of the empyema and the frontal sinus followed by 8 weeks of intravenous antibiotics
2 Streptococcus intermedius is a potential pathogen in which of the following infections Choose ONE answer ONLY from the followingA Liver abscessB Urinary tract infectionC MeningitisD Thoracic empyemaE Pneumonia
3 Which of the following statements regarding lsquopyrexia of unknown originrsquo in children is false Choose ONE answer ONLY from the followingA Malignancy is the underlying pathology in 5ndash15 of
casesB An aetiology will be found in over 90 of casesC The most common cause is infectionD A rheumatological cause is found in 10ndash20 of casesE Familial Mediterranean fever can occur in children of
non-Mediterranean ethnicity
Answers
Case 11 AThe anion gap is a useful tool to differentiate the causes of a metabolic acidosis It is calculated by the equation
Anion gap = [Na K ] [Cl HCO ]3+ + minus minus+ minus +
It represents the effect of unmeasured anions on the plasma pH and is normally 10ndash18 mmollitre
2 CMicrovillus inclusion disease is a severe autosomal recessive enteropathy that is typically apparent within hours or days after birth It is the second most common cause of protracted diarrhoea in the newborn after infectious causes It is characterized by severe yellow watery diarrhoea and malabsorption due to hypoplasia andor atrophy of the villi of the small intestine secondary to an inherited defect in the brush border membrane This results in severe dehydration malnutrition and metabolic acidosis due to bicarbonate loss from the gut
3 CDiagnosis of microvillus inclusion disease is made on small bowel biopsy Electron microscopy findings are of intracellular brush border inclusions and densely packed apical cytoplasmic vesicular bodies indicating microvillous atrophy There is no cure Treatment is supportive with total parenteral nutrition and consideration of small bowel transplantation
Further reAding
Goulet O ruemmele f causes and management of intestinal failure
in children Gastroenterology 2006 130(suppl 1) s16ndash28
rhoads Jm Vogler rc lacey sr et al microvillus inclusion disease
In vitro jejunal electrolyte transport Gastroenterology 1991
100 811ndash817
Case 21 CGianottindashCrosti syndrome is a distinct self-limiting rash commonly associated with viral infections in children between 2 and 6 years of age It presents as multiple pink to redminusbrown papules or papulovesicles which may be pruritic and can become confluent Gianotti and Crosti initially described the exanthema as associated with hepatitis B virus and they termed it papular acrodermatitis of childhood It can occur in several viral diseases eg hepatitis A B and C coxsackie viruses and cytomegalovirus
2 BHepatitis is a syndrome characterized by inflammation or injury of liver cells which may develop into cell necrosis and subsequently fibrosis andor cirrhosis Biochemically there are raised liver enzymes The degree of transaminase elevation does not correlate with the severity of the disease process Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of viral hepatitis
3 DHepatitis B infection is transmitted via blood sexually or vertically Infection may be acute or chronic Diagnostic markers are the presence of surface antigen (HBsAg) and HBV DNA The presence of e antigen (HBeAg) indicates high infectivity Infected newborns have a 95 risk of becoming carriers this risk decreases with infection acquired later in childhood Approximately 15ndash25 of HBV carriers will die from cirrhosis or hepatocellular carcinoma Extrahepatic findings are more common in older children and include membranous glomerulonephritis and GianottiminusCrosti syndrome Fulminant hepatic failure occurs in severe cases resulting in persistent jaundice encephalopathy and coagulopathy Management includes counselling family members monitoring for ongoing liver disease and consideration of antiviral therapy
Further reAding
Brandt O abeck d Gianotti r Burgdorf W Gianotti crosti
syndrome J Am Acad Dermatol 2006 54 136ndash145
slowik mK Jhaveri r hepatitis B and c viruses in infants and
young children Semin Pediatr Infect Dis 2005 16 296ndash305
Case 31 CHypercalcaemia is uncommon in infancy The most common symptoms in this age group are irritability vomiting and constipation It may be a manifestation of Williams syndrome vitamin D or calcium excess as well as disorders associated with reduced bone formation such as hypophosphatasia or increased bone resorption such as malignancy Occasionally
Paediatrics and child health 184 205 copy 2008 elsevier ltd all rights reserved
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-
SympoSium neonatology
bicarbonate system is not a potent buffer however as HCO3minus
and CO2 are readily altered by the body this system plays a very powerful role in pH homeostasis15
Respiratory regulationThe respiratory system adapts within minutes to hours as part of the acute response to acidosis This system modifies pH by balancing production of H+ with ventilatory clearance of CO2
H+ directly stimulates chemoreceptors in the respiratory cen-tre of the brainstem producing an increase in respiratory rate26 The response to respiratory acidosis is very rapid as CO2 easily diffuses across the bloodndashbrain barrier however in metabolic acidosis compensation is delayed until plasma bicarbonate fully equilibrates with cerebrospinal fluid (CSF) bicarbonate There is an inverse relationship between alveolar ventilation and partial pressure of dissolved carbon dioxide (PaCO2) a reduction in alveolar ventilation raises PaCO2 and decreases pH Changes in pH therefore affect alveolar ventilation and conversely changes in alveolar ventilation cause significant changes in pH
Renal regulationThe kidneys provide a delayed but sustained response to acidndashbase imbalances by excreting either acidic or alkaline urine In full-term and preterm babies the capacity for acid excretion and bicarbonate reabsorption is reduced as glomerular filtration rates are low and tubular function immature7 Renal function matures with gestation postnatal age and glucocorticoid and thyroid hormones78 Due to their limited capacity to preserve HCO3
minus newborn infants have lower serum bicarbonate levels and are predisposed to acidosis7
Bicarbonate is not effectively reabsorbed due to its size and electrical charge Instead intraluminal HCO3
minus combines with secreted H+ in tubular luminal fluid to produce carbonic acid which dissociates to give H2O and CO2 This CO2 diffuses into tubular cells combines with intracellular H2O and forms carbonic acid which liberates HCO3
minus and H+ HCO3minus is then
recovered to the circulation by exchange for chloride ions (Clminus) through the basal cell membrane247
Renal acid secretion occurs at all sites except the loop of Henle Primary active transport accounts for 5 and secondary for the remaining 95 of total H+ excretion Secondary trans-port involves an exchange between luminal Na+ and intracel-lular H+ Both ions bind to a membrane transport protein The Na+ concentration gradient between the tubular lumen and cells enables Na+ drag into the cell which generates energy to fuel active H+ excretion into the tubular lumen1ndash47
Quantifying acidosis
Standard base excess is a calculated value derived from PaCO2 and pH It is expressed as the mmollitre of base above or below normal buffer bases required to correct the pH to 74 at a PaCO2 of 40 mmHg A negative base excess or base deficit indicates an acidosis while a positive base excess indicates a relative alkalosis15
Anion gap is the measured difference between anions and cations in the blood
Anion gap = (Na+ + k+) minus (HCO3+Clminus)
paeDiatRiCS anD CHilD HealtH 184 17
Calculation of the anion gap enables clinicians better to define the underlying cause of a metabolic acidosis9 The common causes of an increased anion gap acidosis in neonates include lactic acidosis due to tissue hypoperfusion and hypoxia it may also be seen with certain inborn errors of metabolism and in uraemia910 The anion gap can help distinguish between the rela-tively benign non-anion gap hyperchloraemic acidosis seen in premature infants and a pathological lactic acidosis due to poor end-organ perfusion1011
Strong ion theory
Stewart described a complex acidndashbase model which proposed that H+ concentration results from the dissociation of water which is influenced by PaCO2 the strong ion difference and plasma weak acids12
Strong ions are ions that dissociate at normal body pH and include Na+ K+ and Clminus Weak acids in plasma which contrib-ute include albumin inorganic phosphate and plasma proteins their concentrations do not change with pH and are therefore a constant The effect of these factors and other unmeasured tissue ions on acidndashbase status can be quantified by the calculation of the strong ion gap (SIG)112 In the neonatal unit it is perhaps more important that we consider how principles of this model may relate to acidndashbase status rather than fully to quantify the SIG Theoretically low albumin and phosphate levels which fre-quently occur in premature infants by reducing the concentra-tion of weak acids can produce a relative alkalosis while high phosphate levels in renal failure may contribute to acidosis
Tissue oxygenation
Oxygenation is closely linked to acidndashbase status as optimal cel-lular function requires oxygen to fuel aerobic metabolism and produce energy In hypoxic conditions anaerobic metabolism predominates which is energy inefficient and results in a lactic acidosis1011
Tissue oxygen availability is related to regional blood flow haemoglobin level and haemoglobin oxygen affinity Arterial blood gases measure the partial pressure of dissolved oxygen (PaO2) which represents a small component of total oxygen con-tent the majority being transported bound to haemoglobin The relationship between percentage haemoglobin saturation (SaO2) and PaO2 is described by the sigmoidal oxyhaemoglobin disso-ciation curve which enables us to relate the two measures to each other235 The affinity of haemoglobin for oxygen is altered by local tissue factors Increases in temperature H+ PaCO2 and 23-diphosphoglycerate (DPG) levels shift the oxyhaemoglobin dissociation curve to the right reducing affinity for oxygen Decreases in temperature H+ PaCO2 and 23-DPG levels shift the curve to the left increasing oxygen affinity1ndash35 In the body haemoglobin oxygen affinity continuously changes increasing in the lungs to enable efficient oxygen uptake and decreasing at tissue level to provide efficient oxygen delivery to metabolically active tissues
Avoiding both hypoxia and hyperoxia is important in the neo-natal unit as deleterious effects of hypoxia are seen in infants with pulmonary hypertension1314 while hyperoxia is associated with an increased incidence of retinopathy of prematurity1516
3 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Clinical acidndashbase imbalances
Clinical acidndashbase imbalances can be respiratory metabolic or a mixture of both These abnormalities may be corrected by the acidndashbase regulatory mechanisms in the body in an attempt to maintain normal pH (Figure 1)
Respiratory acidosisThis occurs when any disorder leads to decreased alveolar ventilation Common causes of respiratory acidosis are listed in Table 1 Reduced respiratory clearance of CO2 means more dissolved CO2 accumulates in the plasma leading to increased production of carbonic acid and H+ Through chemoreceptor stimulation respiratory acidosis rapidly alters ventilation in an attempt to reduce CO226 Chemoreceptor mediated ventila-tory increases may only partly adjust in premature infants with underlying lung disease In babies with a sustained respiratory acidosis eg in chronic lung disease then metabolic compen-sation occurs through increased renal excretion of H+ and reabsorption of HCO3
minus slowly restoring pH to around 80 of normal47
paeDiatRiCS anD CHilD HealtH 184 17
The management of PaCO2 levels in infants receiving mechan-ical ventilation has important clinical implications Premature babies have impaired cerebral autoregulation17 and adverse neurological sequelae are reported in association with high PaCO2 levels18ndash20 Ventilation strategies which advocate lsquoper-missive hypercarbiarsquo have been developed to minimize airways damage from mechanical ventilation21 Published data suggest pulmonary benefits however the safe level of PaCO2 remains to be defined in premature infants2021
Respiratory alkalosisThis occurs when more CO2 is excreted than is produced by the body Pathological conditions leading to respiratory alkalosis are rare Hyperventilation in the neonatal setting is often iatrogenic or may be due to disorders in brainstem control of breathing including hypoxicndashischaemic encephalopathy or primary central nervous system abnormalities (see Table 1)
If respiratory alkalosis is sustained it may be compensated for by reduced reabsorption of filtered bicarbonate Reported adverse associations of low PaCO2 include periventricular leuco-malacia and intraventricular haemorrhage1922
K+
H+
Overventilation
CO2 + H2O harr H2CO3 harr H+ + HCO3ndash
Bicarbonate Buffer
Intracellular Buffer
uarr H+ excretionuarr HCO3
ndash absorption
uarr buffered H+
(NH4+ H2PO4
ndash)uarr ventilation rate
RespiratoryAcidosis
MetabolicAcidosis
darr CO2and uarr pH
RespiratoryAlkalosis
MetabolicAlkalosis
darr H+ anduarr pH
darr ventilation rate
uarrCO2
and darr pH
darr H+ excretiondarr HCO3
ndash absorption
uarrH+ and
darr pH
Brain
Brain
Intracellular Buffer
H+
K+
Sepsis
HypoxiaRDS
Metabolismand growth
Diuretics
Airwayobstruction
Neuromuscularproblems
IEM
Gastric losses
+ +
ndash -
Renal BufferRespiratory Buffer
Figure 1 mechanisms for regulation of extracellular pH iem inborn errors of metabolism RDS respiratory distress syndrome
4 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Common causes of acidndashbase imbalances
pH PCO2 H2CO3 Base excess Common neonatal causes
Respiratory acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
uarr normal normal bull upper airway obstruction choanal atresia
pierre-Robin sequence
bull lung abnormalities respiratory distress
syndrome transient tachypneoa of
newborn pneumonia meconium aspiration
syndrome pulmonary hypoplasia
congenital pulmonary malformations
bull Central hypoventilation hypoxic-ischaemic
encephalopathy intracranial haemorrhage
bull neuromuscular insufficiency congenital
myopathies congenital neuropathies
bull iatrogenic inadequate ventilatory settings
Compensated lower limit
of normal
uarr uarr gt+3
metabolic acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
normal darr ltminus3 increased anion gap
bull lactic acidosis sepsis hypoperfusion
shock necrotizing enterocolitis
bull inorganic acidosis inborn errors of
metabolism renal failure
normal anion gap
bull increased gastrointestinal H2Co3 losses
ileostomy diarrhoea
bull Renal tubular acidoses
Compensated lower limit
of normal
darr darr ltminus3
Respiratory alkalosis Uncompensated gt 745 darr normal normal bull iatrogenic excessive ventilatory settings
bull Compensatory hyperventilation hypoxic-
ischaemic encephalopathy
Compensated higher limit
of normal
darr darr ltminus3
metabolic alkalosis Uncompensated gt 745 normal uarr gt+3 bull gastric losses vomiting non-replacement
of excessive nasogastric aspirates
bull thiazide and loop diuretics
bull Hypokalaemia
Compensated higher limit
of normal
uarr uarr gt+3
Table 1
Metabolic acidosisThis frequently affects infants in the neonatal unit and has many causes1011 (see Table 1) There may be overproduction of tissue acid impaired acid clearance gastrointestinal loss of bicarbonate or an exogenous increased acid load eg chloride total paren-teral nutrition (TPN) or albumin1ndash323
Calculation of the anion gap to distinguish an increased anion gap acidosis from a non-anion gap acidosis is important both for treatment and prognosis1011 Acidosis stimulates respiratory compensation but this is limited in unstable infants Similarly renal compensation with improved HCO3
minus conservation is con-strained by tubular immaturity Treatment of the acidosis should be directed at the underlying cause eg hypoxia hypotension or excess Clminus rather than by administration of base
Metabolic alkalosisThis is unusual in neonates and is most frequently seen in infants with chronic lung disease or heart failure who are receiving diuretics Diuretics cause alkalosis by increasing renal fluid and Na+ losses An active process to reabsorb Na+ occurs in tubule cells which through enhanced H+ secretion and HCO3
minus reab-sorption produce alkalosis27
paeDiatRiCS anD CHilD HealtH 184 17
Metabolic alkalosis may also occur with excessive loss of gas-tric contents eg protracted vomiting or inadequate replacement of nasogastric aspirates (see Table 1)
Interpreting blood gases
Blood gas measurements can provide important diagnostic and prognostic information and a systematic approach to blood gas analysis is described in Table 2 The clinical management of infants with abnormal gases requires a good understanding of acidndashbase physiology and tissue oxygenation and an apprecia-tion of factors which may affect the reliability of samples
Arterial blood sampling is the gold standard however indwelling arterial catheters and arterial stab samples are usually restricted to infants who are critically ill or those who require sig-nificant ongoing intervention Gases are most frequently measured in capillary or venous samples which correlate well with arterial samples for PaCO2 pH and base excess in babies and children receiving intensive care These correlations however are not valid in infants with peripheral vasoconstriction and hypotension2324
Non-invasive monitoring techniques may enable us to reduce the frequency of blood gas sampling Transcutaneous monitoring
5 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
A systematic approach to blood gas analysis
1 Collect the relevant information
bull type of gas ndash capillary or arterial
bull Current respiratory support ndash document level
bull transcutaneous Co2 and Sao2 levels
bull Clarify no significant clinical events before sampling
2 pH accept a range between 730 and 745 in newborn
babies this is lower than in older children is there an
alkalosis (pH gt 745) or an acidosis (lt 730)
3 Co2 aim for a range between 45 and 65 kpa a paCo2 level
more than 65 kpa suggests inadequate alveolar ventilation
while less than 45 kpa suggests hyperventilation Correlate
values with non-invasive measures
4 o2 Can only be assessed from arterial gases aim for pao2
between 60 and 80 kpa Correlate results with pulse
oximetry levels
5 HCo3 and base excess normal HCo3 level is between 20 and
24 mmollitre and bases excess +3 to minus3
6 anion gap look at the anion gap and lactate to help identify
the cause of an acidosis normal lactate levels should be less
than 2 mmollitre
7 Respiratory or metabolic compensation look at the pH and
assess whether it is appropriate for the Co2 level or is there
evidence of compensation
8 interpret use both the clinical history and blood gas
findings to help you identify the primary problem aim your
management at treating the underlying cause
9 Reassess if clinical management changes have been made
repeat the blood gas after an appropriate time interval to
ensure improvement
Table 2
provides a highly accurate and reliable method for measuring PaCO2 through the skin it can however be technically difficult may cause tissue damage and is of limited reliability when peripheral perfusion is reduced25 Continuous end-tidal CO2 measurements correlate well with arterial CO2 values in patients with normal ventilation and perfusion however in babies with lung disease alveolar collapse small tidal volumes and rapid respiratory rates can make these measurements unreliable26 Despite its limitations transcutaneous monitoring provides the best method for CO2 trend monitoring in the neonatal intensive care unit (NICU)25
Oxygen saturation levels can be continuously measured non-invasively using pulse oximetry While oximetry is easy to perform and accurate on occasion SaO2 levels obtained may be unreliable when tissue perfusion is poor or with movement artefact SaO2 monitoring is highly sensitive at detecting hypoxia but is limited in detecting hyperoxia as at levels more than 90 small changes in SaO2 may result in unacceptably large increases in PaO227 It is therefore essential that SaO2 alarm limits are set for all neonates receiving respiratory support to detect hypoxia and prevent hyperoxia1627
Continuous non-invasive monitoring provides invaluable information when managing complex infants in the NICU but it does not replace the need for regular blood gas analysis
paeDiatRiCS anD CHilD HealtH 184 17
ReFeRenCeS
1 Kellum Ja Determinants of blood pH in health and disease
Crit Care 2000 4 6ndash14
2 Quigley R Baum m neonatal acid base balance and disturbances
Semin Perinatol 2004 28 97ndash102
3 Brouillette Rt Waxman DH evaluation of the newbornrsquos blood gas
status Clin Chem 1997 43 215ndash221
4 Chan JC acid-base disorders and the kidney Adv Pediatr 1983 30
401ndash471
5 Siggaard-andersen o the pH-log pCo2 blood acidndashbase nomogram
revised Scand J Lab Invest 1962 14 598ndash604
6 Saetta m mortola Jp interaction of hypoxic and hypercapnic stimuli
on breathing pattern in the newborn rat J Appl Physiol 1987 62
506ndash512
7 Baum m Quigley R postnatal renal development in Seldin DW
giebisch g eds the kidney physiology and pathophysiology new
york lippincott Williams and Wilkins 2000 p 703ndash726
8 ortiz la Quan a Weinberg a et al effect of prenatal
dexamethasone on rat renal development Kidney Int 2001 59
1663ndash1669
9 gabow pa Kaehny WD Fennessey pV goodman Si gross pa
Schrier RW Diagnostic importance of an increased serum anion gap
N Engl J Med 1980 303 854ndash858
10 lorenz Jm Kleinman li markarian K oliver m Fernandez J Serum
anion gap in the differential diagnosis of metabolic acidosis in
critically ill newborns J Pediatr 1999 135 751ndash755
11 Deshpande Sa platt mp association between blood lactate and
acid-base status and mortality in ventilated babies Arch Dis Child
1997 76 F15ndash20
12 Stewart pa modern quantitative acid-base chemistry Can J Physiol
Pharmacol 1983 61 1444ndash1461
13 Dakshinamurti S pathophysiologic mechanisms of persistent
pulmonary hypertension of the newborn Pediatr Pulmonol 2005
39 492ndash503
14 mourani pm ivy DD gao D abman SH pulmonary vascular
effects of inhaled nitric oxide and oxygen tension in
bronchopulmonary dysplasia Am J Respir Crit Care Med 2004
170 1006ndash1013
15 Deulofeut R Critz a adams-Chapman i Sola a avoiding hyperoxia
in infants le 1250 g is associated with improved short- and long-
term outcomes J Perinatol 2006 26 700ndash705
16 Chow lC Wright KW Sola a Can changes in clinical practice
decrease the incidence of severe retinopathy of prematurity in very
low birth weight infants Pediatrics 2003 111 339ndash345
17 Boylan gB young K panerai RB Rennie Jm evans DH Dynamic
cerebral autoregulation in sick newborn infants Pediatr Res 2000
48 12ndash17
18 Kaiser JR gauss CH pont mm Williams DK Hypercapnia during
the first 3 days of life is associated with severe intraventricular
hemorrhage in very low birth weight infants J Perinatol 2006 26
279ndash285
19 Fabres J Carlo Wa phillips V Howard g ambalavanan n Both
extremes of arterial carbon dioxide pressure and the magnitude of
fluctuations in arterial carbon dioxide pressure are associated with
severe intraventricular hemorrhage in preterm infants Pediatrics
2007 119 299ndash305
20 thome uH Carroll W Wu tJ et al outcome of extremely preterm
infants randomized at birth to different paCo2 targets during the
first seven days of life Biol Neonate 2006 90 218ndash225
6 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
21 Carlo Wa Stark aR Wright ll et al minimal ventilation to prevent
bronchopulmonary dysplasia in extremely-low-birth-weight infants
J Pediatr 2002 141 370ndash374
22 okumura a Hayakawa F Kato t et al Hypocarbia in preterm
infants with periventricular leukomalacia the relation between
hypocarbia and mechanical ventilation Pediatrics 2001 107
469ndash475
23 peters o Ryan S matthew l Cheng K lunn J Randomised
controlled trial of acetate in preterm neonates receiving parenteral
nutrition Arch Dis Child 1997 77 F12ndash15
24 yildizda D yapiciolu H yilmaz Hl Sertdemir y Correlation of
simultaneously obtained capillary venous and arterial blood gases
of patients in a paediatric intensive care unit Arch Dis Child 2004
89 176ndash180
25 aliwalas ll noble l nesbitt K et al agreement of carbon
dioxide levels measured by arterial transcutaneous and end tidal
methods in preterm infants 28 weeks gestation J Perinatol 2005
25 26ndash29
26 Hagerty JJ Kleinman me Zurakowski D et al accuracy of a new
low-flow sidestream capnography technology in newborns a pilot
study J Perinatol 2002 22 219ndash225
paeDiatRiCS anD CHilD HealtH 184 17
27 poets CF Wilken m Seidenberg J Southall Dp von der Hardt H
Reliability of a pulse oximeter in the detection of hyperoxemia
J Pediatr 1993 122 87ndash90
Practice points
bull a stable extracellular pH is important for optimal cellular
functioning
bull abnormalities in acidndashbase balance are regulated by buffer
systems and the respiratory and renal tract
bull maintaining a stable pH is challenging for newborn babies
due to their high rates of acid production and immature
regulatory mechanisms
bull arterial or capillary blood gases provide an effective way to
monitor acidndashbase balance in newborns
bull Blood gases should be analysed in a structured manner
assessing pH and then respiratory and metabolic components
bull the treatment of acidndashbase abnormalities should be directed
at the underlying problem not merely at correcting pH
7 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Recognition and management of neonatal seizuresmalcolm levene
AbstractSeizures are the most common major manifestation of central nervous
system dysfunction in the newborn there are many causes but perina-
tal asphyxia and haemorrhagicinfarction lesions account for about 75
there is now considerable evidence that frequent but short seizures in
the neonate affect subsequent neurodevelopmental outcome Studies
using eeg or modified continuous tracing of eeg activity (aeeg or CFm)
have shown that there is often electroconvulsive dissociation this re-
fers to poor correlation between electrical seizures and clinical seizures
Commonly used anticonvulsants appear to increase electroconvulsive
dissociation effective management of neonatal seizures has proved very
disappointing and less than 50 of seizures are abolished by first-line
anticonvulsant medication (phenobarbitone or phenytoin) Drugs such
as midazolam and lidocaine may further reduce seizures but require
more evaluation the challenge is to assess new and more effective anti-
convulsants which are themselves associated with little neurotoxicity
Keywords antiepileptic drugs eeg neonatal seizures neurodegeneration
Convulsions are the most common major neurological sign seen in newborn infants and their incidence estimated from large population studies is 26 per 1000 live births1 Premature infants are over four times more likely to have convulsions than full-term infants12 Neonatal status epilepticus (continuous seizure activity lasting 30 min or more) diagnosed clinically is rare and accounts for only 5 of infants with seizures1 although this is now recognized more frequently as the result of continuous EEG monitoring3
Neonatal convulsions are described as presenting in a num-ber of different ways and various seizure types can be seen in the same baby over a number of hours The frequencies of the various patterns of seizure activity are given in Table 1 In very premature babies and to a lesser extent in term infants minor movement abnormalities may be difficult to identify as subtle seizures These include lip smacking tongue thrusting mouth-ing pedalling type movements of the lower limbs or swimming movements of the arms Apnoea can be a common manifesta-tion of subtle seizures The signs can be protean and vary from baby to baby or even in the same baby Virtually any stereotypic
Malcolm Levene MD FMedSc FRCPCH FRCH is Professor and Head of
Department of Paediatrics and Child Health at University of Leeds Leeds
and Honorary Neonatologist at Leeds General Infirmary Leeds UK
paeDiatRiCS anD CHilD HealtH 184 178
movement may be a manifestation of a seizure disorder in the newborn
Aetiology
The more carefully the fitting baby is investigated the more likely it is that a cause for the seizures will be found A number of recent papers have described the aetiology of neonatal con-vulsions after extensive investigations14 Tekgul et al4 recently studied a consecutive group of full-term infants with evidence of neonatal convulsions (recognized both clinically and on EEG) and reported their outcome Table 2 summarizes these data as well as risk of moderate or severe disability for each causative factor Perinatal asphyxia is the commonest cause for convul-sions in term infants with haemorrhagic or ischaemic lesions also being common
Overall the prognosis for the group of term babies with con-vulsions was good 72 had a favourable outcome Where asphyxia (hypoxicndashischaemic insult) is the cause of neonatal convulsions the outcome is poor in 50 The prognosis for neonatal convulsions when they were due to arterial or cere-brovenous infarction or intracranial haemorrhage was generally good Individually inborn errors are a very rare cause of neo-natal convulsions but in view of the treatable nature of some of these it is essential that these be considered and investigated appropriately5
Patterns of seizure activity in the newborn
Movement pattern Frequency ()
Clonic 50
tonic 20
Subtle 10ndash35 depending on maturity
myoclonic 5
Table 1
Cause incidence and outcome of neonatal convulsions in term infants14
Aetiological factor Incidence () Poor outcome ()
asphyxia 38ndash40 50
Cerebral arteriovenous
infarction
20 0
intracranial haemorrhage 12ndash20 13
Congenital cerebral anomaly 5ndash10 100
Hypoglycaemiahypocalcaemia 3ndash19
infection 3ndash20
inborn error of metabolism 1
unknown cause 10ndash13 0
Refers to moderate and severe neurodevelopmental abnormalitynumbers too small to make meaningful predictions
Table 2
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Controversies in the clinical management of neonatal seizures
In recent years we have learnt much more about the neurobi-ology of seizures and their effect on the developing brain The neonatal brain is in a neurophysiologically hyperexcitable state compared to the more mature brain and therefore is more prone to seizure activity This is due largely to a relative excess of GABA neuroreceptors GABA receptors are usually inhibitory but in the immature brain they have a paradoxically excitatory effect This changes at about term in primates and with progressive develop-ment they adopt a neuroinhibitory role6
The propensity to seizures in the neonatal brain makes resolv-ing the balance of risks between continuing seizure activity on the one hand against potentially adverse effects of therapy on the other a very important equation Added to this is the problem of accurately diagnosing neonatal seizures and whether commonly used anticonvulsants are successful in controlling them
These conundrums can be posed as a series of challenging questions which are discussed below
Do neonatal convulsions cause brain injuryConvulsions are a sign of neurological compromise and may indi-cate significant underlying structural brain damage or biochemi-cal disturbance which may cause further brain damage in its own right There has been considerable debate about the scale of the disability that convulsions cause the immature brain over and above that due to the underlying cause Most of our knowledge comes from studies in rodents and these have provided some tentative answers to this question
Seizures in the mature brain lead to neuronal necrosis but studies in very young rat pups whose brain development is somewhat similar to full-term infants have shown that a series of five brief seizures on five successive days does not cause struc-tural neuronal damage but does produce morphological changes in hippocampal neurones and worryingly deficits in the rat learning and visual spatial memory function in adolescent and adult life7 A single prolonged neonatal convulsion in similarly immature rats does not produce any functional effects8 Others have shown that following priming of the neonatal rat brain by short seizures as described above a further insult comprising induction of status epilepticus in the same rats at an older age causes neuronal necrosis9 This has been referred to as the lsquotwo hit hypothesisrsquo10
A more specific question is does seizure activity in an already significantly compromised brain cause additional neuropathol-ogy Wirrell et al11 studied a series of immature rat pups with the induction of an hypoxicndashischaemic (asphyxial) insult fol-lowed by either chemically-induced fits or a control sham pro-cedure In the more severely asphyxiated animals the degree of brain damage was increased significantly in those that had the additional burden of induced seizures
In summary these studies show that the immature brain is more resistant to short frequent post-seizure damage than the mature brain but despite resulting in no loss of neuronal numbers the function of the brain is permanently affected in later life In the asphyxiated brain seizures appear to have an additional adverse effect on brain damage Furthermore the immature brain that has been lsquoprimedrsquo by early seizures is more
paeDiatRiCS anD CHilD HealtH 184 179
vulnerable to status epilepticus later in life It would appear from these data that frequent seizures in the human infant should be stopped and this begs the question as to whether currently used anticonvulsants effectively control neonatal seizures
Can we rely on clinical versus EEG diagnosis of neonatal convulsionsTraditionally the diagnosis of neonatal convulsions has been made by observation and description of the frequency of abnor-mal movements EEG has been technically difficult in the hostile electrical activity of a neonatal intensive care environment and considerable expertise is required for analysis of the trace It is usually not practical to undertake traditional EEG recordings at the time the baby shows abnormal movements More recently various technological developments have allowed more direct investigation of neuronal electrical activity by either video-EEG or compressed recording of the amplitude integrated EEG (aEEG or CFM)
Rennie et al3 at Kingrsquos College Hospital London have under-taken extensive evaluation of video-EEG and have found that this technique detects many convulsions not recognized by a single channel aEEG or CFM trace Of 19 infants with evidence of convulsions on EEG only four were recognized on CFM but this may have been due to the observersrsquo lack of experi-ence with this technique In other centres that have developed appropriate expertise aEEG or CFM has proved more sensitive to the detection of seizures Video-EEG studies have also shown that many movements interpreted by experienced clinicians to be seizures are not associated with abnormal cortical activity Conversely many electrical seizures are not associated with abnormal movements This is referred to as electroconvulsive dissociation
In summary clinical observation alone to detect the fitting baby is unreliable in that it may either over-detect seizure activ-ity which is not present on EEG or under-detect clinical seizures in infants with EEG-proven convulsions The decision as to which babies to treat with antiepileptic drugs therefore becomes somewhat arbitrary
Do anticonvulsants stop neonatal seizuresAlthough neonatal seizures are common there are few random-ized controlled trials assessing the benefits of antiepileptic drugs (AEDs) in the treatment of this condition Phenobarbitone is the most widely used first-line AED and in an Australasian study 95 of neonatologists and paediatric neurologists used this drug as first-line management12 The most commonly used loading dosage is 20 mgkg but regimens of up to 40 mgkg have been recommended (Table 3)13 Four trials have evaluated the effect of phenobarbitone in abolishing neonatal seizures Two of these studies used EEG to monitor response to the drug1415 and one compared phenobarbitone with phenytoin15 In the latter study seizures were completely controlled in only 43 of babies and in the group where phenytoin was the first drug used com-plete seizure control was achieved in 45 This study switched babies from their first AED to the other if complete control was not obtained on EEG monitoring after exposure to first-line therapy In babies who had been given phenobarbitone as first-line therapy seizure control was only achieved in 57 after phenytoin was added In those given phenytoin first complete
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Dosage regimens for first- second- and third-line anticonvulsants in the neonatal period
Loading dose Second loading dose if first
unsuccessfulMaintenance dose
phenobarbitone 20 mgkg by slow iv injection 10 mgkg iv 25ndash5 mgkg od
phenytoin 20 mgkg iv over 20 min not recommended
midazolam 150ndash200 μgkg iv infusion 1 μgkgmin iv infusion increasing to 5 μgkgmin
until favourable response
lidocaine 2 mgkg iv over 10 min 6 mgkgh for 6 h iv then 4 mgkgh for 12 h then
2 mgkgh for 12 h
lorazepam 005ndash01 mgkg by slow iv injection
Diazepam 03ndash04 mgkg iv over 3ndash5 min
lidocaine should not be used if the infant has previously been treated with phenytoin
Table 3
seizure control was achieved with the adding of phenobarbitone in 62
Boylan et al14 assessed the efficacy of phenobarbitone (20ndash40 mgkg iv over 20 min) in 14 babies monitored by video-EEG in only four was there complete abolition of seizures and in the other 10 electroconvulsive seizure activity increased whereas clinical evidence of seizures reduced This has been termed elec-troclinical dissociation and anticonvulsant drug use in the new-born appears to increase this feature They also showed that the babies least likely to respond to the first-line AED are those with the most abnormal background EEG
Two studies have evaluated the use of phenobarbitone in babies who had sustained significant asphyxial insult at birth Hall et al13 compared high-dose phenobarbitone (mean 39 mgkg) versus standard dose (27 mgkg) and reported fewer convul-sions and a significant reduction of severe disability or death in the high dose group (RR 030 CI 010ndash093) A recent study from India16 of babies with hypoxicndashischaemic encephalopathy ran-domized 25 babies to phenobarbitone (20 mgkg loading dose) and compared them with 20 control babies Only 2 of 25 (4) in the phenobarbitone group developed convulsions compared with 8 of 20 (40) in the control group (p = 001) Because of the specific enrolment criteria (asphyxial insult) neither of these studies is strictly comparable to the studies by Painter et al15 and Boylan et al14 whose intention was to assess the efficacy of first-line anticonvulsant therapy on convulsions of any cause diagnosed either clinically or by EEG
Other anticonvulsants used as second- and third-line drugs have been subject to few studies in the newborn Midazolam is administered as a bolus followed by continuous infusion A recent study17 has shown that in 10 of 13 neonates given intravenous midazolam for status epilepticus control of electri-cal seizures was achieved within the first hour of treatment having been previously shown to be refractory to phenobarbi-tone treatment Some of these babies required a second bolus infusion of midazolam to obtain control of all electrographic seizures
In some parts of Europe lidocaine is used as a third-line anti-convulsant Malingre et al18 evaluated 20 infants refractory to
paeDiatRiCS anD CHilD HealtH 184 180
both phenobarbitone and midazolam and who were then given lidocaine by continuous infusion Lidocaine was effective in abolishing electroconvulsive seizures diagnosed by aEEG in 76 of the treatment courses studied No babies developed cardiac arrhythmias a previously reported complication of lidocaine in older patients As a result of pharmacokinetic studies the dosage regimen has been modified (see Table 3)
In summary phenobarbitone is effective in seizure control in less than 50 of babies and even when combined with phe-nytoin the efficacy of these drugs together remains poor More worrying is the observation that phenobarbitone tends to reduce clinically evident seizures thereby giving the clinician a false sense of security whilst having little or no effect on the num-bers of electroconvulsive disorders This has been summarized appropriately as lsquoafter all these years we still love what doesnrsquot workrsquo19 Both midazolam and lidocaine infusions appear to be effective in abolishing severe seizures in some infants resistant to phenobarbitone Lidocaine should not be given to babies previ-ously exposed to phenytoin for fear of a synergistic adverse effect on cardiac rhythm
Do antiepileptic drugs cause brain damageA riskndashbenefit analysis is needed to evaluate the efficacy of anticonvulsants in stopping neonatal seizures which is poor with standard anticonvulsants as discussed above against the risk of administering the anticonvulsant drugs themselves Phenobarbitone has been reported to have adverse effects on the developing brain including inhibition of brain growth20 neuronal toxicity21 and adverse behavioural and cognitive effects into adult life when administered to young animals22 Phenytoin shows unpredictable plasma levels and potential cardiotoxicity
Recent studies have shown an effect of AED exposure on the developing brain by causing neurodegeneration23 Phenytoin administration to immature rat pups at doses which produce serum levels similar to those achieved in human neonates was associated with widespread neuronal death as a result of apop-tosis (programmed cell death) Phenobarbitone had a similar effect when a dosage regimen similar to 40 mgkg was used and
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
this effect was maximal in the more immature brain Diazepam and clonazepam also resulted in a similar effect Midazolam and lidocaine were not tested in this study The combination of phenobarbitone or phenytoin with diazepam had a particularly profound effect on neurodegeneration
In summary recent data suggest that the commonly used AEDs for neonatal convulsions may in themselves cause neuro-degeneration due to apoptosis with lasting effects on develop-ment Many babies with neonatal convulsions are treated with at least two AEDs and this may produce more severe adverse effects than the seizures themselves
Practical management of neonatal seizures
Assimilation of these data and formulation of a rational policy is difficult when faced with a fitting neonate on an intensive care unit and pressure on the medical staff to lsquodo somethingrsquo but it is important to accept that sometimes doing nothing is preferable to using potentially dangerous drugs in a situation which does not warrant such intervention Many babies who have normal interseizure neurological clinical findings and whose seizures are relatively brief and infrequent probably do not need anticon-vulsant medication A normal or near-normal background EEG trace should reassure the clinician that anticonvulsants can be withheld
Some causes of neonatal convulsions are treatable such as meningitis hypoglycaemia hypocalcaemia and inborn errors of metabolism and each baby should be rapidly and carefully investigated for cause of the convulsions
In some babies clinical assessment of seizures is difficult ie when the baby is very sick small or paralyzed Sometimes it may be difficult to assess the significance of certain movement pat-terns Under these circumstances an EEG may prove to be very helpful In many units EEG is not available out of hours and a simple aEEG or CFM is strongly advised Modern instruments are very simple to apply and prolonged or frequent seizures should be identified with only moderate training The printout can be faxed to a more senior doctor if there is doubt as to what is shown on the trace
The balance of knowledge now is that frequent seizures cause additional damage to the developing brain and that treatment to abolish the seizures is warranted Unfortunately there is little evidence that the majority of seizures can be effectively termi-nated by current standard therapy Furthermore it appears that the more abnormal the background EEG the more difficult it is to control the seizures Nevertheless a written protocol for the management of neonatal convulsions is required on each unit Phenobarbitone and phenytoin remain the mainstay of treat-ment although their effectiveness is disappointing There is little to suggest that midazolam is more effective than lidocaine as third-line therapy but lidocaine is precluded if phenytoin has been previously used
In view of the anxiety as to the neurodegenerative effects on the immature brain of most anticonvulsants used in the neonatal period (particularly when multiple drugs are used) it is prefer-able to use only one drug to maximum dosage before introduc-ing a second In addition the duration of anticonvulsants should be minimized and the drugs stopped at the earliest opportu-nity It is my practice to stop anticonvulsants prior to discharge
paeDiatRiCS anD CHilD HealtH 184 18
from hospital if the baby is neurologically normal on clinical examination
REFEREnCES
1 Ronen gm penney S andrews W the epidemiology of clinical
neonatal seizures in newfoundland a population-based study
J Pediatr 1999 134 71ndash75
2 lanska mJ lanska DJ Baumann RJ et al a population-based study
of neonatal seizures in Fayette County Kentucky Neurology 1995
45 724ndash732
3 Rennie Jm Chorley g Boylan gB et al non-expert use of the
cerebral function monitor for neonatal seizure detection Arch Dis
Child Fetal Neonatal Ed 2004 89 F37ndashF40
4 tekgul H gauvreau K Soul J et al the current etoliologic profile
and neurodevelopmental outcome of seizures in term newborn
infants Pediatrics 2006 117 1270ndash1280
5 Surtees R Wolf n treatable neonatal epilepsy Arch Dis Child 2007
92 659ndash661
6 Ben-ari y Holmes gl effects of seizures on developmental
processes in the immature brain Lancet Neurol 2006 5 1055ndash
1063
7 Holmes gl gairsa Jl Chevassus-au-louis n et al Consequences of
neonatal seizures in the rat morphological and behavioral effects
Ann Neurol 1998 44 845ndash857
8 Stafstrom Ce Chronopoulos a thurber S et al age-dependent
cognitive and behavioural deficits following kainic-acid inducing
seizures Epilepsia 1993 34 420ndash432
9 Schmid R tandon p Stafstrom Ce et al effects of neonatal seizures
on subsequent seizure-induced brain injury Neurology 1999 53
1754ndash1761
10 Hoffmann aF Zhao Q Holmes gl Cognitive impairment following
status epilepticus and recurrent seizures during early development
support for the ldquotwo-hit hypothesisrdquo Epilepsy Behav 2004 5
873ndash877
11 Wirrell eC armstrong ea osman lD et al prolonged seizures
exacerbate perinatal hypoxic-ischemic brain damage Pediatr Res
2001 50 445ndash454
12 Carmo KB Barr p Drug treatment of neonatal seizures by
neonatologists and paediatric neurologists J Paediatr Child Health
2005 41 313ndash316
13 Hall Rt Hall FK Daily DK High-dose phenobarbital therapy in term
newborn infants with severe perinatal asphyxia a randomized
prospective study with three-year follow-up J Pediatr 1998 132
345ndash348
14 Boylan gB Rennie Jm pressler Rm et al phenobarbitone neonatal
seizures and video-eeg Arch Dis Child Fetal Neonatal Ed 2002 86
F165ndash170
15 painter mJ Scher mS Stein aD et al phenobarbital compared with
phenytoin for the treatment of neonatal seizures N Engl J Med
1999 341 485ndash489
16 Singh D Kumar p narang a a randomized controlled trial of
phenobarbital in neonates with hypoxic ischemic encephalopathy
J Matern Fetal Neonatal Med 2005 18 391ndash395
17 Castro Conde JR Borges H Domenech martinez e et al midazolam
in neonatal seizures with no response to phenobarbital Neurology
2005 64 876ndash879
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
18 malingre mm Van Rooij lgm Rademaker Cma et al Development
of an optimal lidocaine infusion strategy for neonatal seizures Eur
J Pediatr 2006 165 598ndash604
19 Sankar R painter mJ neonatal seizures after all these years we still
love what doesnrsquot work Neurology 2005 64 776ndash777
20 Diaz J Schain J Bailey Bg phenobarbital-induced brain growth
retardation in artificially reared rat pups Biol Neonate 1977 32 77ndash82
21 mattson RH phenobarbital toxicity in levy RH Dreifuss Fe
mattson RH et al eds antiepipeptic Drugs 3rd edn new york
Raven 1985 p 341ndash355
22 mikati ma Holmes gl Chronopoulos a et al phenobarbital
modifies seizure-related brain injury in the developing brain Ann
Neurol 1994 36 425ndash453
23 Bittigau p Sifringer m genz K et al antiepileptic drugs and
apoptotic neurodegeneration in the developing brain Proc Natl
Acad Sci U S A 2002 99 15089ndash15094
paeDiatRiCS anD CHilD HealtH 184 182
Practice points
bull the clinician needs to be aware that almost any repetitive
stereotype movement pattern can be a manifestation of
neonatal seizures
bull eeg is important in defining neonatal seizures
bull Frequent short-lived seizures have been shown to cause long-
term neurodevelopmental problems
bull Conventional anticonvulsant medication is ineffective in
abolishing neonatal seizures in greater than 50 of cases
bull there is evidence that exposure of the neonatal brain to
multiple anticonvulsants causes neuronal death
bull Future research is needed to evaluate more effective
anticonvulsants for treating this condition
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
Emotional support for families of sick neonatesMarina nicolaou
cristine Glazebrook
AbstractParents of sick neonates experience high levels of stress anxiety and
depression Most interventions with families of sick infants have focused
on fostering the motherndashinfant relationship through the provision of
information about infant developmental needs or through increased
motherndashinfant contact Many of these studies have reported improved
maternal well-being though there are some concerns about the scope
and practicality of large-scale interventions The few studies to have
prioritized emotional support for parents of sick neonates have pro-
duced encouraging results even interventions requiring relatively few re-
sources such as telephone support parent-to-parent support and group
support have been associated with reduced psychological morbidity for
parents The needs of parents can change throughout their infantrsquos hos-
pitalization and not all want or benefit from the provision of additional
support Thus neonatal intensive care units should aim to provide a
varied flexible and sustainable programme of support options Further
research should focus on the needs of fathers
Keywords mental health neonatal intensive care parents
The admission of an infant to neonatal care is acknowledged to be a source of considerable distress for families This review aims to explore evidence for the psychological impact on families of having an infant in neonatal intensive care and to identify evi-dence for the effectiveness of interventions to promote parental well-being It will conclude with recommendations for strategies to support parents of vulnerable infants and suggestions for fur-ther research
Psychological impact of neonatal care for parents
The majority of research examining the effect on parents of having a sick neonate has focused on families of premature or low birthweight infants Such research has found that parents with a sick neonate exhibit high levels of stress compared to normative samples and to parents of healthy full-term infants1 Singer et al2 examined the stress experienced by mothers of high-risk very low birthweight (VLBW) low-risk VLBW and term
Marina Nicolaou MPhil is a Teaching Assistant at the School of
Community Health Sciences University of Nottingham Nottingham UK
Cristine Glazebrook PhD is a Professor of Health Psychology at the School
of Community Health Sciences University of Nottingham Nottingham UK
PaeDiaTrics anD cHilD HealTH 184 196
infants Several self-report measures were used including the Brief Symptom Inventory the Parenting Stress Index (PSI) the Impact on Family Scale and the Family Inventory of Life Events and Changes (FILE) Mothers of VLBW infants had more psycho-logical distress at 1 month compared to mothers of term infants Mothers of high-risk VLBW infants also reported high psycho-logical distress at 2 years and high levels of parenting stress at 3 years Mothers have also been found to have higher stress levels compared to fathers Shaw et al3 examined the prevalence of acute stress disorder (ASD) in 40 parents whose infants were in the neonatal intensive care unit (NICU) Nearly half of the moth-ers (44) met the criteria for ASD although none of the fathers did Furthermore the severity of the symptoms (measured by the number of concurrent symptoms) was greater for the moth-ers than for the fathers3 The reasons behind this difference have been widely speculated with some believing that it is due to the mothersrsquo greater psychological involvement with the infant as evidenced by their general greater vulnerability to postpartum psychological disorder It could also reflect gender differences in coping style
Having an infant who requires intensive medical care repre-sents a significant emotional burden for families Not only is there extreme anxiety surrounding the infantrsquos health and distress for the childrsquos suffering there is also the unfamiliar and intimidating environment of the NICU to adjust to Hopper in her review of the literature identified sources of stress for parents of sick neo-nates as falling into three areas4 Situational factors included the severity of the infantrsquos illness and how parents adapted to the life crisis of having a sick infant Personal factors involved parental emotions about their roles and the instrumental and informa-tional support which were available to them The third area was classified as environmental sources of stress and included the environment of the NICU and the relationship between parents and members of staff This relationship has been examined by several studies in the nursing literature nurses are seen as ide-ally placed to provide the necessary support and information to parents with sick neonates However whilst some studies have shown that supportive and helpful hospital staff can have a posi-tive effect on parents other studies have highlighted the prob-lems and difficulties which can manifest It has been shown that parents and nurses often have very different ideas about issues eg the necessary skills and competencies needed in an NICU or the characteristics that make a lsquogood motherrsquo
Research has shown that there may be a relationship between high levels of parental stress and an increased likelihood of depression5 Postpartum depression is a psychiatric illness which appears in 10ndash15 of postpartum women Its reported preva-lence rates however have ranged from less than 10 up to 306 depending on the instruments used the population exam-ined and the timing of the research Several factors have been found to be associated with postpartum depression including poor social support and infant-related stressors6 Evidence indi-cates that postnatal depression may be underreported and this is of concern since the mental and psychological health of the mother can affect her relationship with her infant and thus the infantrsquos cognitive and emotional development5 Depressed moth-ers appear to look touch and talk to their infants less frequently and also appear to show fewer positive and more negative faces7 The vocalizations of mothers suffering with depression have also
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
been found to be less effective at promoting cognitive growth and learning in infants8
If researchers are interested in finding ways of providing sup-port for families of sick neonates then they must listen to what such families perceive their needs to be in order to avoid increas-ing anxiety and distress Furthermore the provision of appropri-ate support be it emotional informational or social will enhance parental coping abilities increase self-esteem and reduce anxiety It should be noted though that the research conducted around these issues has often taken lsquosupport needsrsquo as being synony-mous with lsquoinformation needsrsquo Such studies have examined the type the amount and quality of information that parents receive and perceive themselves as needing but have not explored in equal depth the perceived emotional support needs of families who have a sick infant In addition the needs of parents may change throughout their infantrsquos illness Ward examined the per-ceived needs of 52 parents of infants in an NICU9 Parents rated the needs of their hospitalized infant as most important along with the need to be reassured Interestingly they ranked their support needs as least important This research was conducted during the first week of the infantsrsquo hospitalization however which would explain the preoccupation of the parents with the infantrsquos health These results demonstrate that if researchers want to find ways of providing emotional support to parents of sick neonates they must be prepared not only to listen to parents but also to be flexible enough to satisfy the parentsrsquo changing needs and expectations
Interventions aimed at supporting parents
Most interventions that been evaluated in controlled studies have focused on supporting the motherndashinfant relationship and provid-ing information on infant development Many of these interven-tions have included the aim of improving the parental emotional state and thus psychological outcomes such as stress or anxi-ety have been assessed However few studies appear to include fathers This means that strategies implemented to provide emo-tional support to families of sick neonates are often derived from interventions tailored for mothers even though fathers may have different emotional needs
A wide range of interventions with mothers and infants has been evaluated in the NICU Increasing motherndashinfant contact through kangaroo care has been found to reduce maternal anxiety1011 and educational programmes delivered to fami-lies in the NICU have also been associated with reduced emo-tional difficulties in parents12ndash14 Kaaresen and colleagues implemented an intervention which consisted of eight sessions before discharge and four home visits all by trained nurses The sample included 71 premature infants in the intervention group 69 premature infants in the control group and 74 infants in the full-term control group The randomized controlled trial found that the intervention reduced parenting stress in both mothers and fathers of premature infants compared to controls to a level equivalent to parents in the term control group13 At 6 months corrected age mothers of preterm infants who had not received the intervention had total PSI scores which were 17 points higher than the mothers of infants born at term (an effect size of 057) A similar study evaluated the efficacy of an educationalndashbehavioural programmendashCreating Opportunities for
PaeDiaTrics anD cHilD HealTH 184 19
Parent Empowerment (COPE) ndash through a randomized controlled trial with 260 families of premature infants14 COPE was a four-phase educationalndashbehavioural programme which began as early as 2ndash4 d after mothers had given birth and continued until 1 week after discharge from the NICU The programme consisted of audiotaped and written infant behaviour information along with photographs which focused on common behaviours and characteristics of premature infants It also included various par-ent activities in the form of a four-phase workbook which aimed to assist mothers in the implementation of the experimental infor-mation COPE was found significantly to reduce maternal stress in the NICU as well as maternal anxiety and depressive symptoms after hospitalization In contrast a cluster randomized trial of a parenting intervention delivered to mothers of very premature infants from soon after birth showed no benefits for parenting stress1 The authors hypothesized that the intervention had not been of sufficient intensity particularly in the weeks surrounding discharge Neonatal care presents a significant barrier to parent-ing in the early weeks following a very preterm birth and so inter-ventions which focus on the developmental needs of infants and the parentndashchild relationship should particularly aim to support parents as they take on the parenting role There was also concern that the intervention had failed to reach those most at risk
Since large-scale projects can be costly to implement and may often fail to reach the families in most need it may be wiser to focus on intervention programmes which are more practical and easier to implement within a neonatal care setting Research has shown that even interventions which are based on one-off meet-ings with parents of sick neonates can be effective Jotzo and Poets examined the effect of an intervention programme aimed at reducing the severity of traumatic responses as a result of giv-ing birth prematurely15 Their programme consisted of a one-off intervention meeting along with additional psychological help throughout the hospitalization of the infant The meeting cov-ered a variety of issues including a reconstruction of the events shortly before and after the infantrsquos birth relaxation techniques discussion of coping strategies available resources and social support and support during emotional outbursts The measures used included the Impact of Event Scale (IES) and the Peritrau-matic Dissociative Experience Questionnaire At discharge the mothers who received the intervention were found to have a significantly lower traumatic impact as a result of premature birth Furthermore fewer mothers in the intervention group showed symptoms of clinically significant psychological trauma at discharge compared to mothers in the control group (36 vs 76)15 The lsquoParents Circle Programrsquo is another intervention with a similar structure16 This consisted of a 90 min session for parents with the aim of enhancing the developing relationship between parents and infants and to offer parents support A total of 104 parents (59 mothers and 45 fathers) and 44 members of hospital staff were asked to evaluate the programme and their results were analysed using content analysis Families reported gaining perspective on their situation feeling supported becom-ing aware of cues and optimizing interactions and becoming aware of available resources Parents and staff alike felt that participating in the intervention helped parents overcome the difficulties associated with the early time of their infantrsquos hos-pitalization Additional studies have also found positive results with fairly minimal interventions including discussion groups
7 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
in the NICU music during kangaroo care and pairing mothers of sick neonates with trained mothers who had been through similar experiences
Parent support programmes
Parent support programmes (PSPs) which are based in NICUs can provide parents with the opportunity to talk to parents who have been in similar situations and also to discuss their emo-tions with professionals who can help them cope with their situa-tion111718 The parent-to-parent support programme for mothers of preterm infants evaluated by Preyde and Ardal included edu-cational parental support group meetings and individual par-ent-to-parent support (primarily telephone support)19 Measures used included the Parental Stressor Scale NICU the State and the Trait Anxiety Inventories and the Beck Depression Inven-tory After 4 months of participation mothers in the intervention group reported lower levels of stress state anxiety and depres-sion compared to control group mothers The authors speculated however that the participants who were able to meet face to face with other parents were those who benefited the most Hurst conducted a comprehensive survey of an NICU-based PSP This PSP was provided in a variety of formats including a weekly parent support group hospital visitation and 24-h telephone sup-port20 Of the 477 participants 303 families used the PSP dur-ing a 2-year evaluation period with 78 using only one form of support and 18 using two forms Of a sub-sample of 48 parents asked to complete an evaluation of the PSP 92 stated that they would recommend such a programme to other parents Furthermore the majority of parents felt that it made them feel supported and helped them deal with their emotions20 This is an indication that such programmes can be very successful in sup-porting parents throughout their infantrsquos hospitalization It also shows that it can be beneficial to give parents several options and formats when it comes to such support services It is impor-tant to consider though that both the Hurst and the Preyde and Ardal studies found that some participants did not find the sup-port programmes helpful even reporting that they had caused them increased stress and anxiety Therefore it should not be assumed that support programmes will suit every individual and will provide the required support for all parents1920 NICUs need to be flexible enough to provide parents with a range of forms of support to choose from
The increased understanding of the strains that parents of sick neonates have to deal with has also led to efforts to improve customary practices in NICUs Family-centred care focuses on infants and their needs and attempts to redefine the relationship between parents and caregivers These practices strive to provide parents with support during their infantrsquos illness by focusing on freely sharing information and on the collaboration between parents and hospital staff Family-centred care has been found to be associated with several beneficial outcomes including improved parental satisfaction increased parental comfort staff satisfaction and decreased parental stress18 Research is already examining these practices and questioning how these can be improved further Such research reflects the increasing effort focused on lsquohumanizingrsquo the environment in NICUs in order to make parents feel more comfortable about spending time with their infants
PaeDiaTrics anD cHilD HealTH 184 19
Conclusion
Surprisingly few interventions have prioritized the provision of emotional support for parents of sick neonates or accounted for the changing needs and wishes of parents over the course of their infantrsquos care Large-scale supportive education-based inter-ventions have been shown to be effective in reducing parental distress However the feasibility and sustainability of such pro-grammes should also be considered Programmes which require significant additional resources can be expensive and there are also issues of training and quality control Interventions which require significant input from parents may also place additional burdens on families making them potentially less accessible to those most at risk Arguably the aim should be to explore ways of providing acceptable and effective informational support which could be complemented by emotional support from health professionals and from other parents in the unit Increasingly studies are exploring the use of computers and multimedia as an engaging flexible and cost-effective method of targeting indi-vidual needs and providing support and information Such com-puter-based and interactive multimedia interventions have been found to be successful with a range of patient groups and could therefore be examined as a complementary method of providing informational support to families with sick neonates
REfEREnCEs
1 Glazebrook c Marlow n israel c et al randomised trial of a
parenting intervention during neonatal intensive care Arch Dis Child
Fetal Neonatal Ed 2007 92 F438ndash443
2 singer lT salvator a Guo s collin M lilien l Baley J Maternal
psychological distress and parenting stress after the birth of a very
low-birth-weight infant JAMA 1999 281 799ndash805
3 shaw rJ Deblois T ikuta l Ginzburg K Fleisher B Koopman c
acute stress disorder among parents of infants in the neonatal
intensive care nursery Psychosomatics 2006 47 206ndash212
4 Hopper a sources of stress for parents of a sick neonate a
literature review Pediatr Nurs 2000 30 29ndash32
5 Davis l edwards H Mohay H wollin J The impact of very
premature birth on the psychological health of mothers Early Hum
Dev 2003 73 61ndash70
6 Bernazzani O saucier J-F David H Borgeat F Psychosocial
predictors of depressive symptomatology level in postpartum
women J Affect Disord 1997 46 39ndash49
7 Field T infants of depressed mothers Infant Behav Dev 1995 18
1ndash13
8 Kaplan Ps Bachorowski J-a Zarlengo-strouse P child-directed
speech produced by mothers with symptoms of depression fails
to promote associative learning in 4-month-old infants Child Dev
1999 70 560ndash570
9 ward K Perceived needs of parents of critically ill infants in
a neonatal intensive care unit (nicU) Pediatr Nurs 2001 27
281ndash286
10 lai Hl chen cJ Peng Tc et al randomized controlled trial of music
during kangaroo care on maternal state anxiety and preterm infantsrsquo
responses Int J Nurs Stud 2006 43 139ndash146
8 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
11 Tallandini Ma scalembra c Kangaroo mother care and mother-
premature infant dyadic interaction Infant Ment Health J 2006 27
251ndash275
12 Ohgi s Fukuda M akiyama T Gima H effect of an early intervention
programme on low birthweight infants with cerebral injuries
J Paediatr Child Health 2004 40 689ndash695
13 Kaaresen Pi ronning Ja Ulvund se Dahl lB a randomized
controlled trial of the effectiveness of an early-intervention program
in reducing parenting stress after preterm birth Pediatrics 2006
118 e9ndash19
14 Melnyk BM Feinstein nF alpert-Gillis l et al reducing premature
infantsrsquo length of stay and improving parentsrsquo mental health
outcomes with the creating opportunities for parent empowerment
(cOPe) neonatal intensive care unit program a randomized
controlled trial Pediatrics 2006 118 e1414ndash1427
15 Jotzo M Poets cF Helping parents cope with the trauma of
premature birth an evaluation of a trauma-preventive psychological
intervention Pediatrics 2005 115 915ndash919
16 Pearson J andersen K evaluation of a program to promote positive
parenting in the neonatal intensive care unit Neonatal Netw 2001
20 43ndash48
17 roman l lindsay J Boger r et al Parent-to-parent support
initiated in the neonatal intensive care unit Res Nurs Health 1995
18 385ndash394
18 Meyer ec coll cTG lester BM Boukydis cFZ McDonough sM Oh w
Family-based intervention improves maternal psychological well-
being and feeding interaction of preterm infants Pediatrics 1994
93 241ndash246
PaeDiaTrics anD cHilD HealTH 184 19
19 Preyde M ardal F effectiveness of a parent ldquobuddyrdquo program for
mothers of very preterm infants in a neonatal intensive care unit
CMAJ 2003 168 969ndash973
20 Hurst i One size does not fit all Parentsrsquo evaluations of a support
program in a newborn intensive care nursery J Perinat Neonatal
Nurs 2006 20 252ndash261
Practice points
bull Parents of sick neonates experience significant distress and
exhibit higher levels of stress anxiety and depression than
parents of healthy infants
bull educational support emotional support and increased
motherndashinfant contact have been shown to promote maternal
well-being
bull emotional support for fathers has been largely neglected in
the research literature
bull Parents benefit from a choice of supportive facilities which
could include face-to-face sessions with health professionals
telephone support hospital visitation parent-to-parent
support and unit-based group support meetings
bull Parentsrsquo support needs can change during their infantrsquos
hospitalization and not all parents want or benefit from the
provision of additional information and emotional support in
the neonatal unit
9 copy 2008 elsevier ltd all rights reserved
Personal Practice
When should enteral feeds be started in preterm infantsnicholas D embleton
AbstractPaediatricians are regularly faced with the question of when best to start
enteral feeds in preterm infants this is important as longer term out-
come may be compromised by sub-optimal nutrition in early life clinical
factors that may affect the decision to start and the risk and benefits
are discussed
Keywords breast milk feeding nutrition parenteral nutrition
Key points in the history
Alice is lsquonutritionally vulnerablersquo and whilst this may not be immediately apparent it will affect her long term outcome Her energy stores are extremely limited and consist primarily of pro-tein She has less than 5 fat and little energy associated with stored glycogen She is losing about 1 gkgd protein equivalent so she needs at least that and a minimum of 50ndash60 kcalkg of energy just to maintain the status quo let alone grow
Her weight is on the 25th centile Review of any antenatal his-tory may reveal whether fetal growth was normal Fetal growth retardation can occur with a weight greater than 10th centile The presence of antenatal absent or reversed end diastolic flow in the umbilical artery indicates poor gut blood flow This increases the risk of necrotizing enterocolitis (NEC) and might suggest a more cautious approach to starting feeds1
She has no important cardiovascular problems but if she were hypotensive gut blood flow may be low There is no umbilical
Nicholas D Embleton BSC (Hons) MBBS (Hons) MD FRCPCH is Consultant in
Neonatal Medicine at Newcastle Neonatal Service Royal Victoria
Infirmary Newcastle upon Tyne NE1 4LP UK
Should you start feeds at a day of age
alice was born following spontaneous labour at 30 weeksrsquo
gestation she weighed 1300 g and is now 18 h old she was
briefly ventilated and then extubated to continuous positive
airway pressure 12 h ago in 35 oxygen she has had caffeine
citrate but still has intermittent episodes of self-correcting
apnoea she was commenced on iv 10 dextrose but this was
replaced by a parenteral amino acid solution (referred to as
lsquotPnrsquo) along with intralipid at 0900 this morning serum glucose
is 11 mmoll and blood pressure is 42 systolic
PaeDiatrics anD cHilD HealtH 184 20
arterial catheter in situ but there is no good evidence that this should delay the decision to start feeds Her glucose is high but this is quite common in a baby like this Could this be a sign of sepsis Caffeine does not affect the incidence of NEC2 The great-est risk factor for NEC in this case is prematurity
What else might be found on examination
Up until 24 h ago she was swallowing large amounts of amniotic fluid What will have changed since then
General examination should confirm peripheral perfusion lsquogestaltrsquo view (does she look lsquowellrsquo) and cardiovascular status lsquoBowel soundsrsquo are not usually helpful
The most important variable likely to affect gut perfusion is the arterial duct Precordial lsquoheaversquo and a loud murmur are sug-gestive but it is possible to have a significant ductal shunt in a baby with a normal examination Cardiac ultrasound will con-firm this diagnosis It might be better to treat a large shunt first with indometacin and to delay starting feeds for a further 24 h
It is not possible to assess gut perfusion clinically but normal perfusion elsewhere (adequate urine output usually indicates adequate renal perfusion) would be reassuring Most preterm babies have a few abdominal lsquoloopsrsquo visible but a distended abdomen with many palpable loops suggests ileus This might be secondary to sepsis or poor gut blood flow Preterm babies do not pass much meconium in the first 24ndash48 h
Balance of risks between starting and withholding feeds
Alice requires 35ndash4 gkgd of protein and 120 kcalkgd to grow3 This will initially be provided parenterally Delaying feeds increases the risk of gut villous atrophy and prolongs the need for lsquototal parenteral nutrition (TPN)rsquo TPN requires intravenous access and so increases the risk of sepsis and when prolonged use is required combined with the lack of enteral feeding may result in hepatic impairment
Delaying feeds may allow a gut that has been chronically under-perfused to re-establish more normal perfusion although normal gut endocrine function digestive enzyme upregulation and motility require a source of intraluminal nutrients1 A recent study suggested benefit from delaying the introduction of feeds4 but methodologi-cal problems exist5 Although a Cochrane meta-analysis suggested no benefit only two studies were included6 A large UK-based trial is examining the effect of early or late feeding in preterm infants who were born growth retarded following identification of antena-tal absent or reversed end diastolic flow in the umbilical artery7
When starting feeds what volume should be used
There are no good data to guide this decision We start with 24 mlkg (1 mlkgh) and then increase by this amount each day Most babies achieve full enteral feeds (ge150 mlkgd) by a week of age Feeding guidelines improve the outcome8 Measure-ment or assessment of gastric aspirates is not consistently useful in predicting subsequent feeding intolerance or development of NEC Aspirate volumes equivalent to or sometimes greater than the amount given in the preceding 1ndash2 h are usually normal Most aspirates have a greenish colour Thick bloody or intensely bile-stained aspirates require detailed assessment
0 copy 2008 elsevier ltd all rights reserved
Personal Practice
What else affects decisions and outcome
Feeding success is affected by sepsis and NEC Scrupulous atten-tion should be paid to hand washing and intravenous access and blood sampling should be minimized There is no good evidence to support the routine use of pro-kinetic agents or H2 blockers
The most important clinical intervention affecting the occur-rence of NEC is the use of breast milk9 All efforts should be directed at persuading parents of the benefits and supporting the process Some clinicians delay starting feeds for a further 24 h whilst expressed breast milk becomes available Donor breast milk might be equally efficacious10
RefeRenceS
1 Dorling J Kempley s leaf a Feeding growth restricted preterm
infants with abnormal antenatal Doppler results Arch Dis Child Fetal
Neonatal Ed 2005 90 F359ndash363
2 schmidt B roberts rs Davis P et al caffeine therapy for apnea of
prematurity N Engl J Med 2006 354 2112ndash2121
PaeDiatrics anD cHilD HealtH 184 20
3 embleton nD Pang n cooke rJ Postnatal malnutrition and growth
retardation an inevitable consequence of current recommendations
in preterm infants Pediatrics 2001 107 270ndash273
4 Berseth cl Bisquera Ja Paje VU Prolonging small feeding volumes
early in life decreases the incidence of necrotizing enterocolitis in
very low birth weight infants Pediatrics 2003 111 529ndash534
5 Menon G Boyle eM embleton nD et al introduction of enteral
feeds in preterm infants Pediatrics 2004 114 327ndash328
6 Kennedy Ka tyson Je chamnanvanikij s early versus delayed
initiation of progressive enteral feedings for parenterally fed low
birth weight or preterm infants Cochrane Database Syst Rev 2000
cD001970
7 wwwnpeuoxacukadept
8 Patole sK de Klerk n impact of standardised feeding regimens on
incidence of neonatal necrotising enterocolitis a systematic review
and meta-analysis of observational studies Arch Dis Child Fetal
Neonatal Ed 2005 90 F147ndash151
9 lucas a cole tJ Breast milk and neonatal necrotising enterocolitis
Lancet 1990 336 1519ndash1523
10 Boyd ca Quigley Ma Brocklehurst P Donor breast milk versus
infant formula for preterm infants systematic review and meta-
analysis Arch Dis Child Fetal Neonatal Ed 2007 92 F169ndash175
1 copy 2008 elsevier ltd all rights reserved
self-assessment
Case 1A term male infant born to consanguineous parents is assessed at 24 h of age due to poor feeding profuse yellow watery diar-rhoea and irritability He weighed 32 kg at birth and delivery was uneventful There was no polyhydramnios He has been breastfed since birth On examination he is pale with a non-tender but distended abdomen and reduced bowel sounds His weight is 275 kg and he looks dehydrated Examination is otherwise normal
Initial investigations (normal values in parentheses) showed
sodium 149 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 65 mmollitre (25ndash75)
creatinine 147 μmollitre (40ndash110)
chloride 119 mmollitre (95ndash105)
haemoglobin 172 gdl (140ndash200)
White blood cell count 80 times 109litre (100ndash260)
Platelet count 302 times 109litre (150ndash400)
arterial blood gas
ph 720 (730ndash745)
PcO2 23 kPa (46ndash60)
Bicarbonate 68 mmollitre (220ndash260)
Base excess minus186 mmollitre (minus20 to +20)
lactate 59 mmollitre (06ndash24)
An abdominal X-ray shows distended bowel loops with no intramural thickening or pneumoperitoneum (Figure 1)
He was given nil by mouth and received intravenous fluids and antibiotics His dehydration improved but the metabolic acidosis and diarrhoea persisted despite receiving no enteral feeds and the commencement of total parenteral nutrition Blood and stool cultures were negative
1 Which of the following best describes these results Choose ONE answer ONLY from the followingA Hypernatraemia hyperchloraemic metabolic acidosis
with increased anion gapB Hypernatraemia hyperchloraemic metabolic acidosis
with normal anion gap
Manish Sadarangani BM BCh MA MRCPCH is Clinical Research Fellow
at the Department of Paediatrics University of Oxford Centre for
Clinical Vaccinology and Tropical Medicine Churchill Hospital
Oxford OX3 7LJ UK
Shabna Rajapaksa MB BChir MA MRCPCH is Specialist Registrar in
Paediatrics at the Paediatric Intensive Care Unit John Radcliffe
Hospital Oxford OX3 9DU UK
Nicholas Mann MD FRCP FRCPCH DCH is Consultant Paediatrician at the
Department of Paediatrics Royal Berkshire Hospital Reading RG1
5AN UK
self-assessment
C Hypernatraemic dehydration and compensated metabolic acidosis
D Acute renal failureE Renal tubular acidosis
2 What is the likely diagnosis Choose ONE answer ONLY from the followingA Hirschsprung disease ndash long segmentB Cystic fibrosis with meconium ileusC Microvillus inclusion diseaseD Cowrsquos milk protein intoleranceE Lactose intolerance
3 What is the investigation of choice Choose ONE answer ONLY from the followingA Rectal biopsy with staining for acetylcholine receptorsB Immunoreactive trypsinC Gastrointestinal endoscopy and biopsyD Stool microscopy and cultureE Stool reducing substances
Case 2A 4-year-old boy presents with a 3 d history of jaundice and a florid rash He has had orange urine and there is no change in his stool colour His family originate from Kosovo and have lived in the UK for the last 8 years He has never left the UK There is no history of blood transfusion or sex-ual abuse The grandmother was recently diagnosed with hepatitis B
On examination he is well apyrexial and mildly jaundiced with cervical and axillary lymphadenopathy He has an exten-sive papular rash over the face extremities and trunk (Figure 2) There is 3 cm hepatomegaly with no splenomegaly or ascites Examination is otherwise normal
Figure 1 abdominal X-ray of baby
Paediatrics and child health 184 202 copy 2008 elsevier ltd all rights reserved
self-assessment
Initial investigations are as follows
haemoglobin 110 gdl (113ndash135)
White blood cell count 108 times 109litre (50ndash150)
Platelet count 278 times 109litre (150ndash400)
inr 10 (08ndash12)
aPt ratio 10 (08ndash13)
sodium 140 mmollitre (135ndash145)
Potassium 42 mmollitre (35ndash50)
Urea 56 mmollitre (25ndash75)
creatinine 65 μmollitre (45ndash120)
total bilirubin 66 μmollitre (0ndash15)
conjugated bilirubin 23 μmollitre (0ndash10)
alanine aminotransferase (alt) 2033 iUlitre (0ndash35)
alkaline phosphatase 987 iUlitre (71ndash234)
Gamma-glutamyl transferase (GGt) 870 iUlitre (0ndash51)
1 What is the name of this rash Choose ONE answer ONLY from the followingA Erythema multiformeB Erythema migransC GianottiminusCrosti syndromeD EczemaE Dermatitis herpetiformis
2 What is the most likely diagnosis Choose ONE Answer ONLY from the followingA Autoimmune hepatitisB Hepatitis BC Hepatitis DD Wilson diseaseE Alpha-1 antitrypsin deficiency
3 What is the best means of management Choose ONE answer ONLY from the followingA Isolation until the jaundice disappearsB ImmunosuppressionC Copper chelating agents and genetic counsellingD Patient and family education with consideration of
antiviral agentsE Liver transplantation
Case 3A 10-month-old boy presents with 3 weeks of vomiting and constipation ndash he is passing hard stools every 2ndash3 days He has fallen from the 9th to below the 04th centile in the last 6 weeks He passed meconium within the first 24 h of life On examina-tion he looks pale and there are some dysmorphic features ndash a short nose long philtrum and wide mouth He has normal heart sounds with a grade 3 ejection systolic murmur loudest at the upper right sternal edge Examination is otherwise normal
Initial investigations are as follows
haemoglobin 91 gdl (113ndash141)
total white blood cell count 124 times 109litre (60ndash170)
Platelet count 407 times 109litre (150ndash400)
sodium 144 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 78 mmollitre (25ndash75)
creatinine 78 μmollitre (45ndash120)
albumin 52 glitre (35ndash50)
corrected calcium 384 mmollitre (238ndash263)
Phosphate 167 mmollitre (099ndash157)
1 What is the most likely diagnosis Choose ONE answer ONLY from the followingA HyperparathyroidismB Acute leukaemiaC Williams syndromeD Hypervitaminosis DE Familial hypocalciuric hypercalcaemia
2 Which investigation would be most useful in establishing the diagnosis Choose ONE answer ONLY from the followingA Intact parathyroid hormone assayB Blood filmC Fluorescent in-situ hybridization for 7q1123 deletionD 25-hydroxyvitamin D assayE Urine calciumcreatinine ratio
3 Which of the following treatments would not be suitable for this patient Choose ONE answer ONLY from the followingA Low calcium dietB Normal saline infusionC FurosemideD CorticosteroidsE Bisphosphonates
Case 4A 10-week-old girl presents with a 2-day history of poor feed-ing Her mother has been concerned about weakness since birth She only has a flicker of movement in the arms none in the legs and has a weak cry She has been passing urine and opening her bowels normally She was born at full term by normal delivery and did not require any resuscitation at birth Normal fetal movements were felt antenatally and there was no polyhydramnios She is the first child of non- consanguineous parents and there is no significant family his-tory On examination she is alert and fixing and following appropriately She has a weak cry and a weak suck There is reduced central and peripheral tone with marked head lag
Figure 2 rash found on examination
Paediatrics and child health 184 203 copy 2008 elsevier ltd all rights reserved
self-assessment
Muscle power is grade 3 out of 5 in the arms and legs There is no muscle or tongue fasciculation and she has absent reflexes throughout The remainder of the examination is normal
Electromyogram shows irregular polyphasic motor unit potentials with marked instability consistent with a dener-vating and re-innervating process (Figure 3)
1 Which of the following additional investigations may be helpful Choose ONE answer ONLY from the followingA Nerve conduction studiesB Creatine kinase assayC Muscle biopsyD SMN1 gene analysisE All of the above
2 What is the most likely cause of this childrsquos symptoms Choose ONE answer ONLY from the followingA Congenital myotonic dystrophyB Duchenne muscular dystrophyC PraderminusWilli syndromeD Spinal muscular atrophyE Mitochondrial myopathy
3 What is the mode of inheritance of this disease Choose ONE answer ONLY from the followingA X-linked recessiveB Autosomal recessiveC Autosomal dominantD MitochondrialE Sporadic
Case 5A 13-year-old girl presents with a 3-week history of fever up to 40degC night sweats and headache She has a reduced appetite with some weight loss She has no other specific symptoms She was on holiday in China 7 months ago On examination she looks well and has a temperature of 387degC There is no lymphadenopathy and no rashes Examination is entirely normal
Results of investigations are as follows
haemoglobin 126 gdl (120ndash160)
total white blood cell count 132 times 109litre (43ndash108)
neutrophil count 115 times 109litre (25ndash75)
Platelet count 244 times 109litre (150ndash400)
Blood film neutrophilia with left shift
erythrocyte sedimentation rate 63 mmh (1ndash20)
c-reactive protein 219 mglitre (0ndash5)
Blood culture Streptococcus intermedius
from anaerobic bottle only
csf culture negative
Magnetic resonance imaging (MRI) of the brain shows acute frontal sinusitis with a large intracranial frontal extra-dural empyema (Figure 4)
1 Which of the following would be appropriate management Choose ONE answer ONLY from the followingA A 12-week course of intravenous antibioticsB Drainage of the frontal sinus followed by 2 weeks of
intravenous antibioticsC Drainage of the empyema followed by 2 weeks of
intravenous antibioticsD Drainage of the empyema and the frontal sinus
followed by 2 weeks of oral antibiotics
1151
1152
1153
1154
1155
1156
1157
1158
1159
1200
50ms 1mV
Figure 3 electromyogram recording from the patient Figure 4 Parasagittal section from mri scan of patient
Paediatrics and child health 184 204 copy 2008 elsevier ltd all rights reserved
self-assessment
E Drainage of the empyema and the frontal sinus followed by 8 weeks of intravenous antibiotics
2 Streptococcus intermedius is a potential pathogen in which of the following infections Choose ONE answer ONLY from the followingA Liver abscessB Urinary tract infectionC MeningitisD Thoracic empyemaE Pneumonia
3 Which of the following statements regarding lsquopyrexia of unknown originrsquo in children is false Choose ONE answer ONLY from the followingA Malignancy is the underlying pathology in 5ndash15 of
casesB An aetiology will be found in over 90 of casesC The most common cause is infectionD A rheumatological cause is found in 10ndash20 of casesE Familial Mediterranean fever can occur in children of
non-Mediterranean ethnicity
Answers
Case 11 AThe anion gap is a useful tool to differentiate the causes of a metabolic acidosis It is calculated by the equation
Anion gap = [Na K ] [Cl HCO ]3+ + minus minus+ minus +
It represents the effect of unmeasured anions on the plasma pH and is normally 10ndash18 mmollitre
2 CMicrovillus inclusion disease is a severe autosomal recessive enteropathy that is typically apparent within hours or days after birth It is the second most common cause of protracted diarrhoea in the newborn after infectious causes It is characterized by severe yellow watery diarrhoea and malabsorption due to hypoplasia andor atrophy of the villi of the small intestine secondary to an inherited defect in the brush border membrane This results in severe dehydration malnutrition and metabolic acidosis due to bicarbonate loss from the gut
3 CDiagnosis of microvillus inclusion disease is made on small bowel biopsy Electron microscopy findings are of intracellular brush border inclusions and densely packed apical cytoplasmic vesicular bodies indicating microvillous atrophy There is no cure Treatment is supportive with total parenteral nutrition and consideration of small bowel transplantation
Further reAding
Goulet O ruemmele f causes and management of intestinal failure
in children Gastroenterology 2006 130(suppl 1) s16ndash28
rhoads Jm Vogler rc lacey sr et al microvillus inclusion disease
In vitro jejunal electrolyte transport Gastroenterology 1991
100 811ndash817
Case 21 CGianottindashCrosti syndrome is a distinct self-limiting rash commonly associated with viral infections in children between 2 and 6 years of age It presents as multiple pink to redminusbrown papules or papulovesicles which may be pruritic and can become confluent Gianotti and Crosti initially described the exanthema as associated with hepatitis B virus and they termed it papular acrodermatitis of childhood It can occur in several viral diseases eg hepatitis A B and C coxsackie viruses and cytomegalovirus
2 BHepatitis is a syndrome characterized by inflammation or injury of liver cells which may develop into cell necrosis and subsequently fibrosis andor cirrhosis Biochemically there are raised liver enzymes The degree of transaminase elevation does not correlate with the severity of the disease process Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of viral hepatitis
3 DHepatitis B infection is transmitted via blood sexually or vertically Infection may be acute or chronic Diagnostic markers are the presence of surface antigen (HBsAg) and HBV DNA The presence of e antigen (HBeAg) indicates high infectivity Infected newborns have a 95 risk of becoming carriers this risk decreases with infection acquired later in childhood Approximately 15ndash25 of HBV carriers will die from cirrhosis or hepatocellular carcinoma Extrahepatic findings are more common in older children and include membranous glomerulonephritis and GianottiminusCrosti syndrome Fulminant hepatic failure occurs in severe cases resulting in persistent jaundice encephalopathy and coagulopathy Management includes counselling family members monitoring for ongoing liver disease and consideration of antiviral therapy
Further reAding
Brandt O abeck d Gianotti r Burgdorf W Gianotti crosti
syndrome J Am Acad Dermatol 2006 54 136ndash145
slowik mK Jhaveri r hepatitis B and c viruses in infants and
young children Semin Pediatr Infect Dis 2005 16 296ndash305
Case 31 CHypercalcaemia is uncommon in infancy The most common symptoms in this age group are irritability vomiting and constipation It may be a manifestation of Williams syndrome vitamin D or calcium excess as well as disorders associated with reduced bone formation such as hypophosphatasia or increased bone resorption such as malignancy Occasionally
Paediatrics and child health 184 205 copy 2008 elsevier ltd all rights reserved
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-
SympoSium neonatology
Clinical acidndashbase imbalances
Clinical acidndashbase imbalances can be respiratory metabolic or a mixture of both These abnormalities may be corrected by the acidndashbase regulatory mechanisms in the body in an attempt to maintain normal pH (Figure 1)
Respiratory acidosisThis occurs when any disorder leads to decreased alveolar ventilation Common causes of respiratory acidosis are listed in Table 1 Reduced respiratory clearance of CO2 means more dissolved CO2 accumulates in the plasma leading to increased production of carbonic acid and H+ Through chemoreceptor stimulation respiratory acidosis rapidly alters ventilation in an attempt to reduce CO226 Chemoreceptor mediated ventila-tory increases may only partly adjust in premature infants with underlying lung disease In babies with a sustained respiratory acidosis eg in chronic lung disease then metabolic compen-sation occurs through increased renal excretion of H+ and reabsorption of HCO3
minus slowly restoring pH to around 80 of normal47
paeDiatRiCS anD CHilD HealtH 184 17
The management of PaCO2 levels in infants receiving mechan-ical ventilation has important clinical implications Premature babies have impaired cerebral autoregulation17 and adverse neurological sequelae are reported in association with high PaCO2 levels18ndash20 Ventilation strategies which advocate lsquoper-missive hypercarbiarsquo have been developed to minimize airways damage from mechanical ventilation21 Published data suggest pulmonary benefits however the safe level of PaCO2 remains to be defined in premature infants2021
Respiratory alkalosisThis occurs when more CO2 is excreted than is produced by the body Pathological conditions leading to respiratory alkalosis are rare Hyperventilation in the neonatal setting is often iatrogenic or may be due to disorders in brainstem control of breathing including hypoxicndashischaemic encephalopathy or primary central nervous system abnormalities (see Table 1)
If respiratory alkalosis is sustained it may be compensated for by reduced reabsorption of filtered bicarbonate Reported adverse associations of low PaCO2 include periventricular leuco-malacia and intraventricular haemorrhage1922
K+
H+
Overventilation
CO2 + H2O harr H2CO3 harr H+ + HCO3ndash
Bicarbonate Buffer
Intracellular Buffer
uarr H+ excretionuarr HCO3
ndash absorption
uarr buffered H+
(NH4+ H2PO4
ndash)uarr ventilation rate
RespiratoryAcidosis
MetabolicAcidosis
darr CO2and uarr pH
RespiratoryAlkalosis
MetabolicAlkalosis
darr H+ anduarr pH
darr ventilation rate
uarrCO2
and darr pH
darr H+ excretiondarr HCO3
ndash absorption
uarrH+ and
darr pH
Brain
Brain
Intracellular Buffer
H+
K+
Sepsis
HypoxiaRDS
Metabolismand growth
Diuretics
Airwayobstruction
Neuromuscularproblems
IEM
Gastric losses
+ +
ndash -
Renal BufferRespiratory Buffer
Figure 1 mechanisms for regulation of extracellular pH iem inborn errors of metabolism RDS respiratory distress syndrome
4 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Common causes of acidndashbase imbalances
pH PCO2 H2CO3 Base excess Common neonatal causes
Respiratory acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
uarr normal normal bull upper airway obstruction choanal atresia
pierre-Robin sequence
bull lung abnormalities respiratory distress
syndrome transient tachypneoa of
newborn pneumonia meconium aspiration
syndrome pulmonary hypoplasia
congenital pulmonary malformations
bull Central hypoventilation hypoxic-ischaemic
encephalopathy intracranial haemorrhage
bull neuromuscular insufficiency congenital
myopathies congenital neuropathies
bull iatrogenic inadequate ventilatory settings
Compensated lower limit
of normal
uarr uarr gt+3
metabolic acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
normal darr ltminus3 increased anion gap
bull lactic acidosis sepsis hypoperfusion
shock necrotizing enterocolitis
bull inorganic acidosis inborn errors of
metabolism renal failure
normal anion gap
bull increased gastrointestinal H2Co3 losses
ileostomy diarrhoea
bull Renal tubular acidoses
Compensated lower limit
of normal
darr darr ltminus3
Respiratory alkalosis Uncompensated gt 745 darr normal normal bull iatrogenic excessive ventilatory settings
bull Compensatory hyperventilation hypoxic-
ischaemic encephalopathy
Compensated higher limit
of normal
darr darr ltminus3
metabolic alkalosis Uncompensated gt 745 normal uarr gt+3 bull gastric losses vomiting non-replacement
of excessive nasogastric aspirates
bull thiazide and loop diuretics
bull Hypokalaemia
Compensated higher limit
of normal
uarr uarr gt+3
Table 1
Metabolic acidosisThis frequently affects infants in the neonatal unit and has many causes1011 (see Table 1) There may be overproduction of tissue acid impaired acid clearance gastrointestinal loss of bicarbonate or an exogenous increased acid load eg chloride total paren-teral nutrition (TPN) or albumin1ndash323
Calculation of the anion gap to distinguish an increased anion gap acidosis from a non-anion gap acidosis is important both for treatment and prognosis1011 Acidosis stimulates respiratory compensation but this is limited in unstable infants Similarly renal compensation with improved HCO3
minus conservation is con-strained by tubular immaturity Treatment of the acidosis should be directed at the underlying cause eg hypoxia hypotension or excess Clminus rather than by administration of base
Metabolic alkalosisThis is unusual in neonates and is most frequently seen in infants with chronic lung disease or heart failure who are receiving diuretics Diuretics cause alkalosis by increasing renal fluid and Na+ losses An active process to reabsorb Na+ occurs in tubule cells which through enhanced H+ secretion and HCO3
minus reab-sorption produce alkalosis27
paeDiatRiCS anD CHilD HealtH 184 17
Metabolic alkalosis may also occur with excessive loss of gas-tric contents eg protracted vomiting or inadequate replacement of nasogastric aspirates (see Table 1)
Interpreting blood gases
Blood gas measurements can provide important diagnostic and prognostic information and a systematic approach to blood gas analysis is described in Table 2 The clinical management of infants with abnormal gases requires a good understanding of acidndashbase physiology and tissue oxygenation and an apprecia-tion of factors which may affect the reliability of samples
Arterial blood sampling is the gold standard however indwelling arterial catheters and arterial stab samples are usually restricted to infants who are critically ill or those who require sig-nificant ongoing intervention Gases are most frequently measured in capillary or venous samples which correlate well with arterial samples for PaCO2 pH and base excess in babies and children receiving intensive care These correlations however are not valid in infants with peripheral vasoconstriction and hypotension2324
Non-invasive monitoring techniques may enable us to reduce the frequency of blood gas sampling Transcutaneous monitoring
5 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
A systematic approach to blood gas analysis
1 Collect the relevant information
bull type of gas ndash capillary or arterial
bull Current respiratory support ndash document level
bull transcutaneous Co2 and Sao2 levels
bull Clarify no significant clinical events before sampling
2 pH accept a range between 730 and 745 in newborn
babies this is lower than in older children is there an
alkalosis (pH gt 745) or an acidosis (lt 730)
3 Co2 aim for a range between 45 and 65 kpa a paCo2 level
more than 65 kpa suggests inadequate alveolar ventilation
while less than 45 kpa suggests hyperventilation Correlate
values with non-invasive measures
4 o2 Can only be assessed from arterial gases aim for pao2
between 60 and 80 kpa Correlate results with pulse
oximetry levels
5 HCo3 and base excess normal HCo3 level is between 20 and
24 mmollitre and bases excess +3 to minus3
6 anion gap look at the anion gap and lactate to help identify
the cause of an acidosis normal lactate levels should be less
than 2 mmollitre
7 Respiratory or metabolic compensation look at the pH and
assess whether it is appropriate for the Co2 level or is there
evidence of compensation
8 interpret use both the clinical history and blood gas
findings to help you identify the primary problem aim your
management at treating the underlying cause
9 Reassess if clinical management changes have been made
repeat the blood gas after an appropriate time interval to
ensure improvement
Table 2
provides a highly accurate and reliable method for measuring PaCO2 through the skin it can however be technically difficult may cause tissue damage and is of limited reliability when peripheral perfusion is reduced25 Continuous end-tidal CO2 measurements correlate well with arterial CO2 values in patients with normal ventilation and perfusion however in babies with lung disease alveolar collapse small tidal volumes and rapid respiratory rates can make these measurements unreliable26 Despite its limitations transcutaneous monitoring provides the best method for CO2 trend monitoring in the neonatal intensive care unit (NICU)25
Oxygen saturation levels can be continuously measured non-invasively using pulse oximetry While oximetry is easy to perform and accurate on occasion SaO2 levels obtained may be unreliable when tissue perfusion is poor or with movement artefact SaO2 monitoring is highly sensitive at detecting hypoxia but is limited in detecting hyperoxia as at levels more than 90 small changes in SaO2 may result in unacceptably large increases in PaO227 It is therefore essential that SaO2 alarm limits are set for all neonates receiving respiratory support to detect hypoxia and prevent hyperoxia1627
Continuous non-invasive monitoring provides invaluable information when managing complex infants in the NICU but it does not replace the need for regular blood gas analysis
paeDiatRiCS anD CHilD HealtH 184 17
ReFeRenCeS
1 Kellum Ja Determinants of blood pH in health and disease
Crit Care 2000 4 6ndash14
2 Quigley R Baum m neonatal acid base balance and disturbances
Semin Perinatol 2004 28 97ndash102
3 Brouillette Rt Waxman DH evaluation of the newbornrsquos blood gas
status Clin Chem 1997 43 215ndash221
4 Chan JC acid-base disorders and the kidney Adv Pediatr 1983 30
401ndash471
5 Siggaard-andersen o the pH-log pCo2 blood acidndashbase nomogram
revised Scand J Lab Invest 1962 14 598ndash604
6 Saetta m mortola Jp interaction of hypoxic and hypercapnic stimuli
on breathing pattern in the newborn rat J Appl Physiol 1987 62
506ndash512
7 Baum m Quigley R postnatal renal development in Seldin DW
giebisch g eds the kidney physiology and pathophysiology new
york lippincott Williams and Wilkins 2000 p 703ndash726
8 ortiz la Quan a Weinberg a et al effect of prenatal
dexamethasone on rat renal development Kidney Int 2001 59
1663ndash1669
9 gabow pa Kaehny WD Fennessey pV goodman Si gross pa
Schrier RW Diagnostic importance of an increased serum anion gap
N Engl J Med 1980 303 854ndash858
10 lorenz Jm Kleinman li markarian K oliver m Fernandez J Serum
anion gap in the differential diagnosis of metabolic acidosis in
critically ill newborns J Pediatr 1999 135 751ndash755
11 Deshpande Sa platt mp association between blood lactate and
acid-base status and mortality in ventilated babies Arch Dis Child
1997 76 F15ndash20
12 Stewart pa modern quantitative acid-base chemistry Can J Physiol
Pharmacol 1983 61 1444ndash1461
13 Dakshinamurti S pathophysiologic mechanisms of persistent
pulmonary hypertension of the newborn Pediatr Pulmonol 2005
39 492ndash503
14 mourani pm ivy DD gao D abman SH pulmonary vascular
effects of inhaled nitric oxide and oxygen tension in
bronchopulmonary dysplasia Am J Respir Crit Care Med 2004
170 1006ndash1013
15 Deulofeut R Critz a adams-Chapman i Sola a avoiding hyperoxia
in infants le 1250 g is associated with improved short- and long-
term outcomes J Perinatol 2006 26 700ndash705
16 Chow lC Wright KW Sola a Can changes in clinical practice
decrease the incidence of severe retinopathy of prematurity in very
low birth weight infants Pediatrics 2003 111 339ndash345
17 Boylan gB young K panerai RB Rennie Jm evans DH Dynamic
cerebral autoregulation in sick newborn infants Pediatr Res 2000
48 12ndash17
18 Kaiser JR gauss CH pont mm Williams DK Hypercapnia during
the first 3 days of life is associated with severe intraventricular
hemorrhage in very low birth weight infants J Perinatol 2006 26
279ndash285
19 Fabres J Carlo Wa phillips V Howard g ambalavanan n Both
extremes of arterial carbon dioxide pressure and the magnitude of
fluctuations in arterial carbon dioxide pressure are associated with
severe intraventricular hemorrhage in preterm infants Pediatrics
2007 119 299ndash305
20 thome uH Carroll W Wu tJ et al outcome of extremely preterm
infants randomized at birth to different paCo2 targets during the
first seven days of life Biol Neonate 2006 90 218ndash225
6 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
21 Carlo Wa Stark aR Wright ll et al minimal ventilation to prevent
bronchopulmonary dysplasia in extremely-low-birth-weight infants
J Pediatr 2002 141 370ndash374
22 okumura a Hayakawa F Kato t et al Hypocarbia in preterm
infants with periventricular leukomalacia the relation between
hypocarbia and mechanical ventilation Pediatrics 2001 107
469ndash475
23 peters o Ryan S matthew l Cheng K lunn J Randomised
controlled trial of acetate in preterm neonates receiving parenteral
nutrition Arch Dis Child 1997 77 F12ndash15
24 yildizda D yapiciolu H yilmaz Hl Sertdemir y Correlation of
simultaneously obtained capillary venous and arterial blood gases
of patients in a paediatric intensive care unit Arch Dis Child 2004
89 176ndash180
25 aliwalas ll noble l nesbitt K et al agreement of carbon
dioxide levels measured by arterial transcutaneous and end tidal
methods in preterm infants 28 weeks gestation J Perinatol 2005
25 26ndash29
26 Hagerty JJ Kleinman me Zurakowski D et al accuracy of a new
low-flow sidestream capnography technology in newborns a pilot
study J Perinatol 2002 22 219ndash225
paeDiatRiCS anD CHilD HealtH 184 17
27 poets CF Wilken m Seidenberg J Southall Dp von der Hardt H
Reliability of a pulse oximeter in the detection of hyperoxemia
J Pediatr 1993 122 87ndash90
Practice points
bull a stable extracellular pH is important for optimal cellular
functioning
bull abnormalities in acidndashbase balance are regulated by buffer
systems and the respiratory and renal tract
bull maintaining a stable pH is challenging for newborn babies
due to their high rates of acid production and immature
regulatory mechanisms
bull arterial or capillary blood gases provide an effective way to
monitor acidndashbase balance in newborns
bull Blood gases should be analysed in a structured manner
assessing pH and then respiratory and metabolic components
bull the treatment of acidndashbase abnormalities should be directed
at the underlying problem not merely at correcting pH
7 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Recognition and management of neonatal seizuresmalcolm levene
AbstractSeizures are the most common major manifestation of central nervous
system dysfunction in the newborn there are many causes but perina-
tal asphyxia and haemorrhagicinfarction lesions account for about 75
there is now considerable evidence that frequent but short seizures in
the neonate affect subsequent neurodevelopmental outcome Studies
using eeg or modified continuous tracing of eeg activity (aeeg or CFm)
have shown that there is often electroconvulsive dissociation this re-
fers to poor correlation between electrical seizures and clinical seizures
Commonly used anticonvulsants appear to increase electroconvulsive
dissociation effective management of neonatal seizures has proved very
disappointing and less than 50 of seizures are abolished by first-line
anticonvulsant medication (phenobarbitone or phenytoin) Drugs such
as midazolam and lidocaine may further reduce seizures but require
more evaluation the challenge is to assess new and more effective anti-
convulsants which are themselves associated with little neurotoxicity
Keywords antiepileptic drugs eeg neonatal seizures neurodegeneration
Convulsions are the most common major neurological sign seen in newborn infants and their incidence estimated from large population studies is 26 per 1000 live births1 Premature infants are over four times more likely to have convulsions than full-term infants12 Neonatal status epilepticus (continuous seizure activity lasting 30 min or more) diagnosed clinically is rare and accounts for only 5 of infants with seizures1 although this is now recognized more frequently as the result of continuous EEG monitoring3
Neonatal convulsions are described as presenting in a num-ber of different ways and various seizure types can be seen in the same baby over a number of hours The frequencies of the various patterns of seizure activity are given in Table 1 In very premature babies and to a lesser extent in term infants minor movement abnormalities may be difficult to identify as subtle seizures These include lip smacking tongue thrusting mouth-ing pedalling type movements of the lower limbs or swimming movements of the arms Apnoea can be a common manifesta-tion of subtle seizures The signs can be protean and vary from baby to baby or even in the same baby Virtually any stereotypic
Malcolm Levene MD FMedSc FRCPCH FRCH is Professor and Head of
Department of Paediatrics and Child Health at University of Leeds Leeds
and Honorary Neonatologist at Leeds General Infirmary Leeds UK
paeDiatRiCS anD CHilD HealtH 184 178
movement may be a manifestation of a seizure disorder in the newborn
Aetiology
The more carefully the fitting baby is investigated the more likely it is that a cause for the seizures will be found A number of recent papers have described the aetiology of neonatal con-vulsions after extensive investigations14 Tekgul et al4 recently studied a consecutive group of full-term infants with evidence of neonatal convulsions (recognized both clinically and on EEG) and reported their outcome Table 2 summarizes these data as well as risk of moderate or severe disability for each causative factor Perinatal asphyxia is the commonest cause for convul-sions in term infants with haemorrhagic or ischaemic lesions also being common
Overall the prognosis for the group of term babies with con-vulsions was good 72 had a favourable outcome Where asphyxia (hypoxicndashischaemic insult) is the cause of neonatal convulsions the outcome is poor in 50 The prognosis for neonatal convulsions when they were due to arterial or cere-brovenous infarction or intracranial haemorrhage was generally good Individually inborn errors are a very rare cause of neo-natal convulsions but in view of the treatable nature of some of these it is essential that these be considered and investigated appropriately5
Patterns of seizure activity in the newborn
Movement pattern Frequency ()
Clonic 50
tonic 20
Subtle 10ndash35 depending on maturity
myoclonic 5
Table 1
Cause incidence and outcome of neonatal convulsions in term infants14
Aetiological factor Incidence () Poor outcome ()
asphyxia 38ndash40 50
Cerebral arteriovenous
infarction
20 0
intracranial haemorrhage 12ndash20 13
Congenital cerebral anomaly 5ndash10 100
Hypoglycaemiahypocalcaemia 3ndash19
infection 3ndash20
inborn error of metabolism 1
unknown cause 10ndash13 0
Refers to moderate and severe neurodevelopmental abnormalitynumbers too small to make meaningful predictions
Table 2
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Controversies in the clinical management of neonatal seizures
In recent years we have learnt much more about the neurobi-ology of seizures and their effect on the developing brain The neonatal brain is in a neurophysiologically hyperexcitable state compared to the more mature brain and therefore is more prone to seizure activity This is due largely to a relative excess of GABA neuroreceptors GABA receptors are usually inhibitory but in the immature brain they have a paradoxically excitatory effect This changes at about term in primates and with progressive develop-ment they adopt a neuroinhibitory role6
The propensity to seizures in the neonatal brain makes resolv-ing the balance of risks between continuing seizure activity on the one hand against potentially adverse effects of therapy on the other a very important equation Added to this is the problem of accurately diagnosing neonatal seizures and whether commonly used anticonvulsants are successful in controlling them
These conundrums can be posed as a series of challenging questions which are discussed below
Do neonatal convulsions cause brain injuryConvulsions are a sign of neurological compromise and may indi-cate significant underlying structural brain damage or biochemi-cal disturbance which may cause further brain damage in its own right There has been considerable debate about the scale of the disability that convulsions cause the immature brain over and above that due to the underlying cause Most of our knowledge comes from studies in rodents and these have provided some tentative answers to this question
Seizures in the mature brain lead to neuronal necrosis but studies in very young rat pups whose brain development is somewhat similar to full-term infants have shown that a series of five brief seizures on five successive days does not cause struc-tural neuronal damage but does produce morphological changes in hippocampal neurones and worryingly deficits in the rat learning and visual spatial memory function in adolescent and adult life7 A single prolonged neonatal convulsion in similarly immature rats does not produce any functional effects8 Others have shown that following priming of the neonatal rat brain by short seizures as described above a further insult comprising induction of status epilepticus in the same rats at an older age causes neuronal necrosis9 This has been referred to as the lsquotwo hit hypothesisrsquo10
A more specific question is does seizure activity in an already significantly compromised brain cause additional neuropathol-ogy Wirrell et al11 studied a series of immature rat pups with the induction of an hypoxicndashischaemic (asphyxial) insult fol-lowed by either chemically-induced fits or a control sham pro-cedure In the more severely asphyxiated animals the degree of brain damage was increased significantly in those that had the additional burden of induced seizures
In summary these studies show that the immature brain is more resistant to short frequent post-seizure damage than the mature brain but despite resulting in no loss of neuronal numbers the function of the brain is permanently affected in later life In the asphyxiated brain seizures appear to have an additional adverse effect on brain damage Furthermore the immature brain that has been lsquoprimedrsquo by early seizures is more
paeDiatRiCS anD CHilD HealtH 184 179
vulnerable to status epilepticus later in life It would appear from these data that frequent seizures in the human infant should be stopped and this begs the question as to whether currently used anticonvulsants effectively control neonatal seizures
Can we rely on clinical versus EEG diagnosis of neonatal convulsionsTraditionally the diagnosis of neonatal convulsions has been made by observation and description of the frequency of abnor-mal movements EEG has been technically difficult in the hostile electrical activity of a neonatal intensive care environment and considerable expertise is required for analysis of the trace It is usually not practical to undertake traditional EEG recordings at the time the baby shows abnormal movements More recently various technological developments have allowed more direct investigation of neuronal electrical activity by either video-EEG or compressed recording of the amplitude integrated EEG (aEEG or CFM)
Rennie et al3 at Kingrsquos College Hospital London have under-taken extensive evaluation of video-EEG and have found that this technique detects many convulsions not recognized by a single channel aEEG or CFM trace Of 19 infants with evidence of convulsions on EEG only four were recognized on CFM but this may have been due to the observersrsquo lack of experi-ence with this technique In other centres that have developed appropriate expertise aEEG or CFM has proved more sensitive to the detection of seizures Video-EEG studies have also shown that many movements interpreted by experienced clinicians to be seizures are not associated with abnormal cortical activity Conversely many electrical seizures are not associated with abnormal movements This is referred to as electroconvulsive dissociation
In summary clinical observation alone to detect the fitting baby is unreliable in that it may either over-detect seizure activ-ity which is not present on EEG or under-detect clinical seizures in infants with EEG-proven convulsions The decision as to which babies to treat with antiepileptic drugs therefore becomes somewhat arbitrary
Do anticonvulsants stop neonatal seizuresAlthough neonatal seizures are common there are few random-ized controlled trials assessing the benefits of antiepileptic drugs (AEDs) in the treatment of this condition Phenobarbitone is the most widely used first-line AED and in an Australasian study 95 of neonatologists and paediatric neurologists used this drug as first-line management12 The most commonly used loading dosage is 20 mgkg but regimens of up to 40 mgkg have been recommended (Table 3)13 Four trials have evaluated the effect of phenobarbitone in abolishing neonatal seizures Two of these studies used EEG to monitor response to the drug1415 and one compared phenobarbitone with phenytoin15 In the latter study seizures were completely controlled in only 43 of babies and in the group where phenytoin was the first drug used com-plete seizure control was achieved in 45 This study switched babies from their first AED to the other if complete control was not obtained on EEG monitoring after exposure to first-line therapy In babies who had been given phenobarbitone as first-line therapy seizure control was only achieved in 57 after phenytoin was added In those given phenytoin first complete
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Dosage regimens for first- second- and third-line anticonvulsants in the neonatal period
Loading dose Second loading dose if first
unsuccessfulMaintenance dose
phenobarbitone 20 mgkg by slow iv injection 10 mgkg iv 25ndash5 mgkg od
phenytoin 20 mgkg iv over 20 min not recommended
midazolam 150ndash200 μgkg iv infusion 1 μgkgmin iv infusion increasing to 5 μgkgmin
until favourable response
lidocaine 2 mgkg iv over 10 min 6 mgkgh for 6 h iv then 4 mgkgh for 12 h then
2 mgkgh for 12 h
lorazepam 005ndash01 mgkg by slow iv injection
Diazepam 03ndash04 mgkg iv over 3ndash5 min
lidocaine should not be used if the infant has previously been treated with phenytoin
Table 3
seizure control was achieved with the adding of phenobarbitone in 62
Boylan et al14 assessed the efficacy of phenobarbitone (20ndash40 mgkg iv over 20 min) in 14 babies monitored by video-EEG in only four was there complete abolition of seizures and in the other 10 electroconvulsive seizure activity increased whereas clinical evidence of seizures reduced This has been termed elec-troclinical dissociation and anticonvulsant drug use in the new-born appears to increase this feature They also showed that the babies least likely to respond to the first-line AED are those with the most abnormal background EEG
Two studies have evaluated the use of phenobarbitone in babies who had sustained significant asphyxial insult at birth Hall et al13 compared high-dose phenobarbitone (mean 39 mgkg) versus standard dose (27 mgkg) and reported fewer convul-sions and a significant reduction of severe disability or death in the high dose group (RR 030 CI 010ndash093) A recent study from India16 of babies with hypoxicndashischaemic encephalopathy ran-domized 25 babies to phenobarbitone (20 mgkg loading dose) and compared them with 20 control babies Only 2 of 25 (4) in the phenobarbitone group developed convulsions compared with 8 of 20 (40) in the control group (p = 001) Because of the specific enrolment criteria (asphyxial insult) neither of these studies is strictly comparable to the studies by Painter et al15 and Boylan et al14 whose intention was to assess the efficacy of first-line anticonvulsant therapy on convulsions of any cause diagnosed either clinically or by EEG
Other anticonvulsants used as second- and third-line drugs have been subject to few studies in the newborn Midazolam is administered as a bolus followed by continuous infusion A recent study17 has shown that in 10 of 13 neonates given intravenous midazolam for status epilepticus control of electri-cal seizures was achieved within the first hour of treatment having been previously shown to be refractory to phenobarbi-tone treatment Some of these babies required a second bolus infusion of midazolam to obtain control of all electrographic seizures
In some parts of Europe lidocaine is used as a third-line anti-convulsant Malingre et al18 evaluated 20 infants refractory to
paeDiatRiCS anD CHilD HealtH 184 180
both phenobarbitone and midazolam and who were then given lidocaine by continuous infusion Lidocaine was effective in abolishing electroconvulsive seizures diagnosed by aEEG in 76 of the treatment courses studied No babies developed cardiac arrhythmias a previously reported complication of lidocaine in older patients As a result of pharmacokinetic studies the dosage regimen has been modified (see Table 3)
In summary phenobarbitone is effective in seizure control in less than 50 of babies and even when combined with phe-nytoin the efficacy of these drugs together remains poor More worrying is the observation that phenobarbitone tends to reduce clinically evident seizures thereby giving the clinician a false sense of security whilst having little or no effect on the num-bers of electroconvulsive disorders This has been summarized appropriately as lsquoafter all these years we still love what doesnrsquot workrsquo19 Both midazolam and lidocaine infusions appear to be effective in abolishing severe seizures in some infants resistant to phenobarbitone Lidocaine should not be given to babies previ-ously exposed to phenytoin for fear of a synergistic adverse effect on cardiac rhythm
Do antiepileptic drugs cause brain damageA riskndashbenefit analysis is needed to evaluate the efficacy of anticonvulsants in stopping neonatal seizures which is poor with standard anticonvulsants as discussed above against the risk of administering the anticonvulsant drugs themselves Phenobarbitone has been reported to have adverse effects on the developing brain including inhibition of brain growth20 neuronal toxicity21 and adverse behavioural and cognitive effects into adult life when administered to young animals22 Phenytoin shows unpredictable plasma levels and potential cardiotoxicity
Recent studies have shown an effect of AED exposure on the developing brain by causing neurodegeneration23 Phenytoin administration to immature rat pups at doses which produce serum levels similar to those achieved in human neonates was associated with widespread neuronal death as a result of apop-tosis (programmed cell death) Phenobarbitone had a similar effect when a dosage regimen similar to 40 mgkg was used and
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
this effect was maximal in the more immature brain Diazepam and clonazepam also resulted in a similar effect Midazolam and lidocaine were not tested in this study The combination of phenobarbitone or phenytoin with diazepam had a particularly profound effect on neurodegeneration
In summary recent data suggest that the commonly used AEDs for neonatal convulsions may in themselves cause neuro-degeneration due to apoptosis with lasting effects on develop-ment Many babies with neonatal convulsions are treated with at least two AEDs and this may produce more severe adverse effects than the seizures themselves
Practical management of neonatal seizures
Assimilation of these data and formulation of a rational policy is difficult when faced with a fitting neonate on an intensive care unit and pressure on the medical staff to lsquodo somethingrsquo but it is important to accept that sometimes doing nothing is preferable to using potentially dangerous drugs in a situation which does not warrant such intervention Many babies who have normal interseizure neurological clinical findings and whose seizures are relatively brief and infrequent probably do not need anticon-vulsant medication A normal or near-normal background EEG trace should reassure the clinician that anticonvulsants can be withheld
Some causes of neonatal convulsions are treatable such as meningitis hypoglycaemia hypocalcaemia and inborn errors of metabolism and each baby should be rapidly and carefully investigated for cause of the convulsions
In some babies clinical assessment of seizures is difficult ie when the baby is very sick small or paralyzed Sometimes it may be difficult to assess the significance of certain movement pat-terns Under these circumstances an EEG may prove to be very helpful In many units EEG is not available out of hours and a simple aEEG or CFM is strongly advised Modern instruments are very simple to apply and prolonged or frequent seizures should be identified with only moderate training The printout can be faxed to a more senior doctor if there is doubt as to what is shown on the trace
The balance of knowledge now is that frequent seizures cause additional damage to the developing brain and that treatment to abolish the seizures is warranted Unfortunately there is little evidence that the majority of seizures can be effectively termi-nated by current standard therapy Furthermore it appears that the more abnormal the background EEG the more difficult it is to control the seizures Nevertheless a written protocol for the management of neonatal convulsions is required on each unit Phenobarbitone and phenytoin remain the mainstay of treat-ment although their effectiveness is disappointing There is little to suggest that midazolam is more effective than lidocaine as third-line therapy but lidocaine is precluded if phenytoin has been previously used
In view of the anxiety as to the neurodegenerative effects on the immature brain of most anticonvulsants used in the neonatal period (particularly when multiple drugs are used) it is prefer-able to use only one drug to maximum dosage before introduc-ing a second In addition the duration of anticonvulsants should be minimized and the drugs stopped at the earliest opportu-nity It is my practice to stop anticonvulsants prior to discharge
paeDiatRiCS anD CHilD HealtH 184 18
from hospital if the baby is neurologically normal on clinical examination
REFEREnCES
1 Ronen gm penney S andrews W the epidemiology of clinical
neonatal seizures in newfoundland a population-based study
J Pediatr 1999 134 71ndash75
2 lanska mJ lanska DJ Baumann RJ et al a population-based study
of neonatal seizures in Fayette County Kentucky Neurology 1995
45 724ndash732
3 Rennie Jm Chorley g Boylan gB et al non-expert use of the
cerebral function monitor for neonatal seizure detection Arch Dis
Child Fetal Neonatal Ed 2004 89 F37ndashF40
4 tekgul H gauvreau K Soul J et al the current etoliologic profile
and neurodevelopmental outcome of seizures in term newborn
infants Pediatrics 2006 117 1270ndash1280
5 Surtees R Wolf n treatable neonatal epilepsy Arch Dis Child 2007
92 659ndash661
6 Ben-ari y Holmes gl effects of seizures on developmental
processes in the immature brain Lancet Neurol 2006 5 1055ndash
1063
7 Holmes gl gairsa Jl Chevassus-au-louis n et al Consequences of
neonatal seizures in the rat morphological and behavioral effects
Ann Neurol 1998 44 845ndash857
8 Stafstrom Ce Chronopoulos a thurber S et al age-dependent
cognitive and behavioural deficits following kainic-acid inducing
seizures Epilepsia 1993 34 420ndash432
9 Schmid R tandon p Stafstrom Ce et al effects of neonatal seizures
on subsequent seizure-induced brain injury Neurology 1999 53
1754ndash1761
10 Hoffmann aF Zhao Q Holmes gl Cognitive impairment following
status epilepticus and recurrent seizures during early development
support for the ldquotwo-hit hypothesisrdquo Epilepsy Behav 2004 5
873ndash877
11 Wirrell eC armstrong ea osman lD et al prolonged seizures
exacerbate perinatal hypoxic-ischemic brain damage Pediatr Res
2001 50 445ndash454
12 Carmo KB Barr p Drug treatment of neonatal seizures by
neonatologists and paediatric neurologists J Paediatr Child Health
2005 41 313ndash316
13 Hall Rt Hall FK Daily DK High-dose phenobarbital therapy in term
newborn infants with severe perinatal asphyxia a randomized
prospective study with three-year follow-up J Pediatr 1998 132
345ndash348
14 Boylan gB Rennie Jm pressler Rm et al phenobarbitone neonatal
seizures and video-eeg Arch Dis Child Fetal Neonatal Ed 2002 86
F165ndash170
15 painter mJ Scher mS Stein aD et al phenobarbital compared with
phenytoin for the treatment of neonatal seizures N Engl J Med
1999 341 485ndash489
16 Singh D Kumar p narang a a randomized controlled trial of
phenobarbital in neonates with hypoxic ischemic encephalopathy
J Matern Fetal Neonatal Med 2005 18 391ndash395
17 Castro Conde JR Borges H Domenech martinez e et al midazolam
in neonatal seizures with no response to phenobarbital Neurology
2005 64 876ndash879
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
18 malingre mm Van Rooij lgm Rademaker Cma et al Development
of an optimal lidocaine infusion strategy for neonatal seizures Eur
J Pediatr 2006 165 598ndash604
19 Sankar R painter mJ neonatal seizures after all these years we still
love what doesnrsquot work Neurology 2005 64 776ndash777
20 Diaz J Schain J Bailey Bg phenobarbital-induced brain growth
retardation in artificially reared rat pups Biol Neonate 1977 32 77ndash82
21 mattson RH phenobarbital toxicity in levy RH Dreifuss Fe
mattson RH et al eds antiepipeptic Drugs 3rd edn new york
Raven 1985 p 341ndash355
22 mikati ma Holmes gl Chronopoulos a et al phenobarbital
modifies seizure-related brain injury in the developing brain Ann
Neurol 1994 36 425ndash453
23 Bittigau p Sifringer m genz K et al antiepileptic drugs and
apoptotic neurodegeneration in the developing brain Proc Natl
Acad Sci U S A 2002 99 15089ndash15094
paeDiatRiCS anD CHilD HealtH 184 182
Practice points
bull the clinician needs to be aware that almost any repetitive
stereotype movement pattern can be a manifestation of
neonatal seizures
bull eeg is important in defining neonatal seizures
bull Frequent short-lived seizures have been shown to cause long-
term neurodevelopmental problems
bull Conventional anticonvulsant medication is ineffective in
abolishing neonatal seizures in greater than 50 of cases
bull there is evidence that exposure of the neonatal brain to
multiple anticonvulsants causes neuronal death
bull Future research is needed to evaluate more effective
anticonvulsants for treating this condition
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
Emotional support for families of sick neonatesMarina nicolaou
cristine Glazebrook
AbstractParents of sick neonates experience high levels of stress anxiety and
depression Most interventions with families of sick infants have focused
on fostering the motherndashinfant relationship through the provision of
information about infant developmental needs or through increased
motherndashinfant contact Many of these studies have reported improved
maternal well-being though there are some concerns about the scope
and practicality of large-scale interventions The few studies to have
prioritized emotional support for parents of sick neonates have pro-
duced encouraging results even interventions requiring relatively few re-
sources such as telephone support parent-to-parent support and group
support have been associated with reduced psychological morbidity for
parents The needs of parents can change throughout their infantrsquos hos-
pitalization and not all want or benefit from the provision of additional
support Thus neonatal intensive care units should aim to provide a
varied flexible and sustainable programme of support options Further
research should focus on the needs of fathers
Keywords mental health neonatal intensive care parents
The admission of an infant to neonatal care is acknowledged to be a source of considerable distress for families This review aims to explore evidence for the psychological impact on families of having an infant in neonatal intensive care and to identify evi-dence for the effectiveness of interventions to promote parental well-being It will conclude with recommendations for strategies to support parents of vulnerable infants and suggestions for fur-ther research
Psychological impact of neonatal care for parents
The majority of research examining the effect on parents of having a sick neonate has focused on families of premature or low birthweight infants Such research has found that parents with a sick neonate exhibit high levels of stress compared to normative samples and to parents of healthy full-term infants1 Singer et al2 examined the stress experienced by mothers of high-risk very low birthweight (VLBW) low-risk VLBW and term
Marina Nicolaou MPhil is a Teaching Assistant at the School of
Community Health Sciences University of Nottingham Nottingham UK
Cristine Glazebrook PhD is a Professor of Health Psychology at the School
of Community Health Sciences University of Nottingham Nottingham UK
PaeDiaTrics anD cHilD HealTH 184 196
infants Several self-report measures were used including the Brief Symptom Inventory the Parenting Stress Index (PSI) the Impact on Family Scale and the Family Inventory of Life Events and Changes (FILE) Mothers of VLBW infants had more psycho-logical distress at 1 month compared to mothers of term infants Mothers of high-risk VLBW infants also reported high psycho-logical distress at 2 years and high levels of parenting stress at 3 years Mothers have also been found to have higher stress levels compared to fathers Shaw et al3 examined the prevalence of acute stress disorder (ASD) in 40 parents whose infants were in the neonatal intensive care unit (NICU) Nearly half of the moth-ers (44) met the criteria for ASD although none of the fathers did Furthermore the severity of the symptoms (measured by the number of concurrent symptoms) was greater for the moth-ers than for the fathers3 The reasons behind this difference have been widely speculated with some believing that it is due to the mothersrsquo greater psychological involvement with the infant as evidenced by their general greater vulnerability to postpartum psychological disorder It could also reflect gender differences in coping style
Having an infant who requires intensive medical care repre-sents a significant emotional burden for families Not only is there extreme anxiety surrounding the infantrsquos health and distress for the childrsquos suffering there is also the unfamiliar and intimidating environment of the NICU to adjust to Hopper in her review of the literature identified sources of stress for parents of sick neo-nates as falling into three areas4 Situational factors included the severity of the infantrsquos illness and how parents adapted to the life crisis of having a sick infant Personal factors involved parental emotions about their roles and the instrumental and informa-tional support which were available to them The third area was classified as environmental sources of stress and included the environment of the NICU and the relationship between parents and members of staff This relationship has been examined by several studies in the nursing literature nurses are seen as ide-ally placed to provide the necessary support and information to parents with sick neonates However whilst some studies have shown that supportive and helpful hospital staff can have a posi-tive effect on parents other studies have highlighted the prob-lems and difficulties which can manifest It has been shown that parents and nurses often have very different ideas about issues eg the necessary skills and competencies needed in an NICU or the characteristics that make a lsquogood motherrsquo
Research has shown that there may be a relationship between high levels of parental stress and an increased likelihood of depression5 Postpartum depression is a psychiatric illness which appears in 10ndash15 of postpartum women Its reported preva-lence rates however have ranged from less than 10 up to 306 depending on the instruments used the population exam-ined and the timing of the research Several factors have been found to be associated with postpartum depression including poor social support and infant-related stressors6 Evidence indi-cates that postnatal depression may be underreported and this is of concern since the mental and psychological health of the mother can affect her relationship with her infant and thus the infantrsquos cognitive and emotional development5 Depressed moth-ers appear to look touch and talk to their infants less frequently and also appear to show fewer positive and more negative faces7 The vocalizations of mothers suffering with depression have also
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
been found to be less effective at promoting cognitive growth and learning in infants8
If researchers are interested in finding ways of providing sup-port for families of sick neonates then they must listen to what such families perceive their needs to be in order to avoid increas-ing anxiety and distress Furthermore the provision of appropri-ate support be it emotional informational or social will enhance parental coping abilities increase self-esteem and reduce anxiety It should be noted though that the research conducted around these issues has often taken lsquosupport needsrsquo as being synony-mous with lsquoinformation needsrsquo Such studies have examined the type the amount and quality of information that parents receive and perceive themselves as needing but have not explored in equal depth the perceived emotional support needs of families who have a sick infant In addition the needs of parents may change throughout their infantrsquos illness Ward examined the per-ceived needs of 52 parents of infants in an NICU9 Parents rated the needs of their hospitalized infant as most important along with the need to be reassured Interestingly they ranked their support needs as least important This research was conducted during the first week of the infantsrsquo hospitalization however which would explain the preoccupation of the parents with the infantrsquos health These results demonstrate that if researchers want to find ways of providing emotional support to parents of sick neonates they must be prepared not only to listen to parents but also to be flexible enough to satisfy the parentsrsquo changing needs and expectations
Interventions aimed at supporting parents
Most interventions that been evaluated in controlled studies have focused on supporting the motherndashinfant relationship and provid-ing information on infant development Many of these interven-tions have included the aim of improving the parental emotional state and thus psychological outcomes such as stress or anxi-ety have been assessed However few studies appear to include fathers This means that strategies implemented to provide emo-tional support to families of sick neonates are often derived from interventions tailored for mothers even though fathers may have different emotional needs
A wide range of interventions with mothers and infants has been evaluated in the NICU Increasing motherndashinfant contact through kangaroo care has been found to reduce maternal anxiety1011 and educational programmes delivered to fami-lies in the NICU have also been associated with reduced emo-tional difficulties in parents12ndash14 Kaaresen and colleagues implemented an intervention which consisted of eight sessions before discharge and four home visits all by trained nurses The sample included 71 premature infants in the intervention group 69 premature infants in the control group and 74 infants in the full-term control group The randomized controlled trial found that the intervention reduced parenting stress in both mothers and fathers of premature infants compared to controls to a level equivalent to parents in the term control group13 At 6 months corrected age mothers of preterm infants who had not received the intervention had total PSI scores which were 17 points higher than the mothers of infants born at term (an effect size of 057) A similar study evaluated the efficacy of an educationalndashbehavioural programmendashCreating Opportunities for
PaeDiaTrics anD cHilD HealTH 184 19
Parent Empowerment (COPE) ndash through a randomized controlled trial with 260 families of premature infants14 COPE was a four-phase educationalndashbehavioural programme which began as early as 2ndash4 d after mothers had given birth and continued until 1 week after discharge from the NICU The programme consisted of audiotaped and written infant behaviour information along with photographs which focused on common behaviours and characteristics of premature infants It also included various par-ent activities in the form of a four-phase workbook which aimed to assist mothers in the implementation of the experimental infor-mation COPE was found significantly to reduce maternal stress in the NICU as well as maternal anxiety and depressive symptoms after hospitalization In contrast a cluster randomized trial of a parenting intervention delivered to mothers of very premature infants from soon after birth showed no benefits for parenting stress1 The authors hypothesized that the intervention had not been of sufficient intensity particularly in the weeks surrounding discharge Neonatal care presents a significant barrier to parent-ing in the early weeks following a very preterm birth and so inter-ventions which focus on the developmental needs of infants and the parentndashchild relationship should particularly aim to support parents as they take on the parenting role There was also concern that the intervention had failed to reach those most at risk
Since large-scale projects can be costly to implement and may often fail to reach the families in most need it may be wiser to focus on intervention programmes which are more practical and easier to implement within a neonatal care setting Research has shown that even interventions which are based on one-off meet-ings with parents of sick neonates can be effective Jotzo and Poets examined the effect of an intervention programme aimed at reducing the severity of traumatic responses as a result of giv-ing birth prematurely15 Their programme consisted of a one-off intervention meeting along with additional psychological help throughout the hospitalization of the infant The meeting cov-ered a variety of issues including a reconstruction of the events shortly before and after the infantrsquos birth relaxation techniques discussion of coping strategies available resources and social support and support during emotional outbursts The measures used included the Impact of Event Scale (IES) and the Peritrau-matic Dissociative Experience Questionnaire At discharge the mothers who received the intervention were found to have a significantly lower traumatic impact as a result of premature birth Furthermore fewer mothers in the intervention group showed symptoms of clinically significant psychological trauma at discharge compared to mothers in the control group (36 vs 76)15 The lsquoParents Circle Programrsquo is another intervention with a similar structure16 This consisted of a 90 min session for parents with the aim of enhancing the developing relationship between parents and infants and to offer parents support A total of 104 parents (59 mothers and 45 fathers) and 44 members of hospital staff were asked to evaluate the programme and their results were analysed using content analysis Families reported gaining perspective on their situation feeling supported becom-ing aware of cues and optimizing interactions and becoming aware of available resources Parents and staff alike felt that participating in the intervention helped parents overcome the difficulties associated with the early time of their infantrsquos hos-pitalization Additional studies have also found positive results with fairly minimal interventions including discussion groups
7 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
in the NICU music during kangaroo care and pairing mothers of sick neonates with trained mothers who had been through similar experiences
Parent support programmes
Parent support programmes (PSPs) which are based in NICUs can provide parents with the opportunity to talk to parents who have been in similar situations and also to discuss their emo-tions with professionals who can help them cope with their situa-tion111718 The parent-to-parent support programme for mothers of preterm infants evaluated by Preyde and Ardal included edu-cational parental support group meetings and individual par-ent-to-parent support (primarily telephone support)19 Measures used included the Parental Stressor Scale NICU the State and the Trait Anxiety Inventories and the Beck Depression Inven-tory After 4 months of participation mothers in the intervention group reported lower levels of stress state anxiety and depres-sion compared to control group mothers The authors speculated however that the participants who were able to meet face to face with other parents were those who benefited the most Hurst conducted a comprehensive survey of an NICU-based PSP This PSP was provided in a variety of formats including a weekly parent support group hospital visitation and 24-h telephone sup-port20 Of the 477 participants 303 families used the PSP dur-ing a 2-year evaluation period with 78 using only one form of support and 18 using two forms Of a sub-sample of 48 parents asked to complete an evaluation of the PSP 92 stated that they would recommend such a programme to other parents Furthermore the majority of parents felt that it made them feel supported and helped them deal with their emotions20 This is an indication that such programmes can be very successful in sup-porting parents throughout their infantrsquos hospitalization It also shows that it can be beneficial to give parents several options and formats when it comes to such support services It is impor-tant to consider though that both the Hurst and the Preyde and Ardal studies found that some participants did not find the sup-port programmes helpful even reporting that they had caused them increased stress and anxiety Therefore it should not be assumed that support programmes will suit every individual and will provide the required support for all parents1920 NICUs need to be flexible enough to provide parents with a range of forms of support to choose from
The increased understanding of the strains that parents of sick neonates have to deal with has also led to efforts to improve customary practices in NICUs Family-centred care focuses on infants and their needs and attempts to redefine the relationship between parents and caregivers These practices strive to provide parents with support during their infantrsquos illness by focusing on freely sharing information and on the collaboration between parents and hospital staff Family-centred care has been found to be associated with several beneficial outcomes including improved parental satisfaction increased parental comfort staff satisfaction and decreased parental stress18 Research is already examining these practices and questioning how these can be improved further Such research reflects the increasing effort focused on lsquohumanizingrsquo the environment in NICUs in order to make parents feel more comfortable about spending time with their infants
PaeDiaTrics anD cHilD HealTH 184 19
Conclusion
Surprisingly few interventions have prioritized the provision of emotional support for parents of sick neonates or accounted for the changing needs and wishes of parents over the course of their infantrsquos care Large-scale supportive education-based inter-ventions have been shown to be effective in reducing parental distress However the feasibility and sustainability of such pro-grammes should also be considered Programmes which require significant additional resources can be expensive and there are also issues of training and quality control Interventions which require significant input from parents may also place additional burdens on families making them potentially less accessible to those most at risk Arguably the aim should be to explore ways of providing acceptable and effective informational support which could be complemented by emotional support from health professionals and from other parents in the unit Increasingly studies are exploring the use of computers and multimedia as an engaging flexible and cost-effective method of targeting indi-vidual needs and providing support and information Such com-puter-based and interactive multimedia interventions have been found to be successful with a range of patient groups and could therefore be examined as a complementary method of providing informational support to families with sick neonates
REfEREnCEs
1 Glazebrook c Marlow n israel c et al randomised trial of a
parenting intervention during neonatal intensive care Arch Dis Child
Fetal Neonatal Ed 2007 92 F438ndash443
2 singer lT salvator a Guo s collin M lilien l Baley J Maternal
psychological distress and parenting stress after the birth of a very
low-birth-weight infant JAMA 1999 281 799ndash805
3 shaw rJ Deblois T ikuta l Ginzburg K Fleisher B Koopman c
acute stress disorder among parents of infants in the neonatal
intensive care nursery Psychosomatics 2006 47 206ndash212
4 Hopper a sources of stress for parents of a sick neonate a
literature review Pediatr Nurs 2000 30 29ndash32
5 Davis l edwards H Mohay H wollin J The impact of very
premature birth on the psychological health of mothers Early Hum
Dev 2003 73 61ndash70
6 Bernazzani O saucier J-F David H Borgeat F Psychosocial
predictors of depressive symptomatology level in postpartum
women J Affect Disord 1997 46 39ndash49
7 Field T infants of depressed mothers Infant Behav Dev 1995 18
1ndash13
8 Kaplan Ps Bachorowski J-a Zarlengo-strouse P child-directed
speech produced by mothers with symptoms of depression fails
to promote associative learning in 4-month-old infants Child Dev
1999 70 560ndash570
9 ward K Perceived needs of parents of critically ill infants in
a neonatal intensive care unit (nicU) Pediatr Nurs 2001 27
281ndash286
10 lai Hl chen cJ Peng Tc et al randomized controlled trial of music
during kangaroo care on maternal state anxiety and preterm infantsrsquo
responses Int J Nurs Stud 2006 43 139ndash146
8 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
11 Tallandini Ma scalembra c Kangaroo mother care and mother-
premature infant dyadic interaction Infant Ment Health J 2006 27
251ndash275
12 Ohgi s Fukuda M akiyama T Gima H effect of an early intervention
programme on low birthweight infants with cerebral injuries
J Paediatr Child Health 2004 40 689ndash695
13 Kaaresen Pi ronning Ja Ulvund se Dahl lB a randomized
controlled trial of the effectiveness of an early-intervention program
in reducing parenting stress after preterm birth Pediatrics 2006
118 e9ndash19
14 Melnyk BM Feinstein nF alpert-Gillis l et al reducing premature
infantsrsquo length of stay and improving parentsrsquo mental health
outcomes with the creating opportunities for parent empowerment
(cOPe) neonatal intensive care unit program a randomized
controlled trial Pediatrics 2006 118 e1414ndash1427
15 Jotzo M Poets cF Helping parents cope with the trauma of
premature birth an evaluation of a trauma-preventive psychological
intervention Pediatrics 2005 115 915ndash919
16 Pearson J andersen K evaluation of a program to promote positive
parenting in the neonatal intensive care unit Neonatal Netw 2001
20 43ndash48
17 roman l lindsay J Boger r et al Parent-to-parent support
initiated in the neonatal intensive care unit Res Nurs Health 1995
18 385ndash394
18 Meyer ec coll cTG lester BM Boukydis cFZ McDonough sM Oh w
Family-based intervention improves maternal psychological well-
being and feeding interaction of preterm infants Pediatrics 1994
93 241ndash246
PaeDiaTrics anD cHilD HealTH 184 19
19 Preyde M ardal F effectiveness of a parent ldquobuddyrdquo program for
mothers of very preterm infants in a neonatal intensive care unit
CMAJ 2003 168 969ndash973
20 Hurst i One size does not fit all Parentsrsquo evaluations of a support
program in a newborn intensive care nursery J Perinat Neonatal
Nurs 2006 20 252ndash261
Practice points
bull Parents of sick neonates experience significant distress and
exhibit higher levels of stress anxiety and depression than
parents of healthy infants
bull educational support emotional support and increased
motherndashinfant contact have been shown to promote maternal
well-being
bull emotional support for fathers has been largely neglected in
the research literature
bull Parents benefit from a choice of supportive facilities which
could include face-to-face sessions with health professionals
telephone support hospital visitation parent-to-parent
support and unit-based group support meetings
bull Parentsrsquo support needs can change during their infantrsquos
hospitalization and not all parents want or benefit from the
provision of additional information and emotional support in
the neonatal unit
9 copy 2008 elsevier ltd all rights reserved
Personal Practice
When should enteral feeds be started in preterm infantsnicholas D embleton
AbstractPaediatricians are regularly faced with the question of when best to start
enteral feeds in preterm infants this is important as longer term out-
come may be compromised by sub-optimal nutrition in early life clinical
factors that may affect the decision to start and the risk and benefits
are discussed
Keywords breast milk feeding nutrition parenteral nutrition
Key points in the history
Alice is lsquonutritionally vulnerablersquo and whilst this may not be immediately apparent it will affect her long term outcome Her energy stores are extremely limited and consist primarily of pro-tein She has less than 5 fat and little energy associated with stored glycogen She is losing about 1 gkgd protein equivalent so she needs at least that and a minimum of 50ndash60 kcalkg of energy just to maintain the status quo let alone grow
Her weight is on the 25th centile Review of any antenatal his-tory may reveal whether fetal growth was normal Fetal growth retardation can occur with a weight greater than 10th centile The presence of antenatal absent or reversed end diastolic flow in the umbilical artery indicates poor gut blood flow This increases the risk of necrotizing enterocolitis (NEC) and might suggest a more cautious approach to starting feeds1
She has no important cardiovascular problems but if she were hypotensive gut blood flow may be low There is no umbilical
Nicholas D Embleton BSC (Hons) MBBS (Hons) MD FRCPCH is Consultant in
Neonatal Medicine at Newcastle Neonatal Service Royal Victoria
Infirmary Newcastle upon Tyne NE1 4LP UK
Should you start feeds at a day of age
alice was born following spontaneous labour at 30 weeksrsquo
gestation she weighed 1300 g and is now 18 h old she was
briefly ventilated and then extubated to continuous positive
airway pressure 12 h ago in 35 oxygen she has had caffeine
citrate but still has intermittent episodes of self-correcting
apnoea she was commenced on iv 10 dextrose but this was
replaced by a parenteral amino acid solution (referred to as
lsquotPnrsquo) along with intralipid at 0900 this morning serum glucose
is 11 mmoll and blood pressure is 42 systolic
PaeDiatrics anD cHilD HealtH 184 20
arterial catheter in situ but there is no good evidence that this should delay the decision to start feeds Her glucose is high but this is quite common in a baby like this Could this be a sign of sepsis Caffeine does not affect the incidence of NEC2 The great-est risk factor for NEC in this case is prematurity
What else might be found on examination
Up until 24 h ago she was swallowing large amounts of amniotic fluid What will have changed since then
General examination should confirm peripheral perfusion lsquogestaltrsquo view (does she look lsquowellrsquo) and cardiovascular status lsquoBowel soundsrsquo are not usually helpful
The most important variable likely to affect gut perfusion is the arterial duct Precordial lsquoheaversquo and a loud murmur are sug-gestive but it is possible to have a significant ductal shunt in a baby with a normal examination Cardiac ultrasound will con-firm this diagnosis It might be better to treat a large shunt first with indometacin and to delay starting feeds for a further 24 h
It is not possible to assess gut perfusion clinically but normal perfusion elsewhere (adequate urine output usually indicates adequate renal perfusion) would be reassuring Most preterm babies have a few abdominal lsquoloopsrsquo visible but a distended abdomen with many palpable loops suggests ileus This might be secondary to sepsis or poor gut blood flow Preterm babies do not pass much meconium in the first 24ndash48 h
Balance of risks between starting and withholding feeds
Alice requires 35ndash4 gkgd of protein and 120 kcalkgd to grow3 This will initially be provided parenterally Delaying feeds increases the risk of gut villous atrophy and prolongs the need for lsquototal parenteral nutrition (TPN)rsquo TPN requires intravenous access and so increases the risk of sepsis and when prolonged use is required combined with the lack of enteral feeding may result in hepatic impairment
Delaying feeds may allow a gut that has been chronically under-perfused to re-establish more normal perfusion although normal gut endocrine function digestive enzyme upregulation and motility require a source of intraluminal nutrients1 A recent study suggested benefit from delaying the introduction of feeds4 but methodologi-cal problems exist5 Although a Cochrane meta-analysis suggested no benefit only two studies were included6 A large UK-based trial is examining the effect of early or late feeding in preterm infants who were born growth retarded following identification of antena-tal absent or reversed end diastolic flow in the umbilical artery7
When starting feeds what volume should be used
There are no good data to guide this decision We start with 24 mlkg (1 mlkgh) and then increase by this amount each day Most babies achieve full enteral feeds (ge150 mlkgd) by a week of age Feeding guidelines improve the outcome8 Measure-ment or assessment of gastric aspirates is not consistently useful in predicting subsequent feeding intolerance or development of NEC Aspirate volumes equivalent to or sometimes greater than the amount given in the preceding 1ndash2 h are usually normal Most aspirates have a greenish colour Thick bloody or intensely bile-stained aspirates require detailed assessment
0 copy 2008 elsevier ltd all rights reserved
Personal Practice
What else affects decisions and outcome
Feeding success is affected by sepsis and NEC Scrupulous atten-tion should be paid to hand washing and intravenous access and blood sampling should be minimized There is no good evidence to support the routine use of pro-kinetic agents or H2 blockers
The most important clinical intervention affecting the occur-rence of NEC is the use of breast milk9 All efforts should be directed at persuading parents of the benefits and supporting the process Some clinicians delay starting feeds for a further 24 h whilst expressed breast milk becomes available Donor breast milk might be equally efficacious10
RefeRenceS
1 Dorling J Kempley s leaf a Feeding growth restricted preterm
infants with abnormal antenatal Doppler results Arch Dis Child Fetal
Neonatal Ed 2005 90 F359ndash363
2 schmidt B roberts rs Davis P et al caffeine therapy for apnea of
prematurity N Engl J Med 2006 354 2112ndash2121
PaeDiatrics anD cHilD HealtH 184 20
3 embleton nD Pang n cooke rJ Postnatal malnutrition and growth
retardation an inevitable consequence of current recommendations
in preterm infants Pediatrics 2001 107 270ndash273
4 Berseth cl Bisquera Ja Paje VU Prolonging small feeding volumes
early in life decreases the incidence of necrotizing enterocolitis in
very low birth weight infants Pediatrics 2003 111 529ndash534
5 Menon G Boyle eM embleton nD et al introduction of enteral
feeds in preterm infants Pediatrics 2004 114 327ndash328
6 Kennedy Ka tyson Je chamnanvanikij s early versus delayed
initiation of progressive enteral feedings for parenterally fed low
birth weight or preterm infants Cochrane Database Syst Rev 2000
cD001970
7 wwwnpeuoxacukadept
8 Patole sK de Klerk n impact of standardised feeding regimens on
incidence of neonatal necrotising enterocolitis a systematic review
and meta-analysis of observational studies Arch Dis Child Fetal
Neonatal Ed 2005 90 F147ndash151
9 lucas a cole tJ Breast milk and neonatal necrotising enterocolitis
Lancet 1990 336 1519ndash1523
10 Boyd ca Quigley Ma Brocklehurst P Donor breast milk versus
infant formula for preterm infants systematic review and meta-
analysis Arch Dis Child Fetal Neonatal Ed 2007 92 F169ndash175
1 copy 2008 elsevier ltd all rights reserved
self-assessment
Case 1A term male infant born to consanguineous parents is assessed at 24 h of age due to poor feeding profuse yellow watery diar-rhoea and irritability He weighed 32 kg at birth and delivery was uneventful There was no polyhydramnios He has been breastfed since birth On examination he is pale with a non-tender but distended abdomen and reduced bowel sounds His weight is 275 kg and he looks dehydrated Examination is otherwise normal
Initial investigations (normal values in parentheses) showed
sodium 149 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 65 mmollitre (25ndash75)
creatinine 147 μmollitre (40ndash110)
chloride 119 mmollitre (95ndash105)
haemoglobin 172 gdl (140ndash200)
White blood cell count 80 times 109litre (100ndash260)
Platelet count 302 times 109litre (150ndash400)
arterial blood gas
ph 720 (730ndash745)
PcO2 23 kPa (46ndash60)
Bicarbonate 68 mmollitre (220ndash260)
Base excess minus186 mmollitre (minus20 to +20)
lactate 59 mmollitre (06ndash24)
An abdominal X-ray shows distended bowel loops with no intramural thickening or pneumoperitoneum (Figure 1)
He was given nil by mouth and received intravenous fluids and antibiotics His dehydration improved but the metabolic acidosis and diarrhoea persisted despite receiving no enteral feeds and the commencement of total parenteral nutrition Blood and stool cultures were negative
1 Which of the following best describes these results Choose ONE answer ONLY from the followingA Hypernatraemia hyperchloraemic metabolic acidosis
with increased anion gapB Hypernatraemia hyperchloraemic metabolic acidosis
with normal anion gap
Manish Sadarangani BM BCh MA MRCPCH is Clinical Research Fellow
at the Department of Paediatrics University of Oxford Centre for
Clinical Vaccinology and Tropical Medicine Churchill Hospital
Oxford OX3 7LJ UK
Shabna Rajapaksa MB BChir MA MRCPCH is Specialist Registrar in
Paediatrics at the Paediatric Intensive Care Unit John Radcliffe
Hospital Oxford OX3 9DU UK
Nicholas Mann MD FRCP FRCPCH DCH is Consultant Paediatrician at the
Department of Paediatrics Royal Berkshire Hospital Reading RG1
5AN UK
self-assessment
C Hypernatraemic dehydration and compensated metabolic acidosis
D Acute renal failureE Renal tubular acidosis
2 What is the likely diagnosis Choose ONE answer ONLY from the followingA Hirschsprung disease ndash long segmentB Cystic fibrosis with meconium ileusC Microvillus inclusion diseaseD Cowrsquos milk protein intoleranceE Lactose intolerance
3 What is the investigation of choice Choose ONE answer ONLY from the followingA Rectal biopsy with staining for acetylcholine receptorsB Immunoreactive trypsinC Gastrointestinal endoscopy and biopsyD Stool microscopy and cultureE Stool reducing substances
Case 2A 4-year-old boy presents with a 3 d history of jaundice and a florid rash He has had orange urine and there is no change in his stool colour His family originate from Kosovo and have lived in the UK for the last 8 years He has never left the UK There is no history of blood transfusion or sex-ual abuse The grandmother was recently diagnosed with hepatitis B
On examination he is well apyrexial and mildly jaundiced with cervical and axillary lymphadenopathy He has an exten-sive papular rash over the face extremities and trunk (Figure 2) There is 3 cm hepatomegaly with no splenomegaly or ascites Examination is otherwise normal
Figure 1 abdominal X-ray of baby
Paediatrics and child health 184 202 copy 2008 elsevier ltd all rights reserved
self-assessment
Initial investigations are as follows
haemoglobin 110 gdl (113ndash135)
White blood cell count 108 times 109litre (50ndash150)
Platelet count 278 times 109litre (150ndash400)
inr 10 (08ndash12)
aPt ratio 10 (08ndash13)
sodium 140 mmollitre (135ndash145)
Potassium 42 mmollitre (35ndash50)
Urea 56 mmollitre (25ndash75)
creatinine 65 μmollitre (45ndash120)
total bilirubin 66 μmollitre (0ndash15)
conjugated bilirubin 23 μmollitre (0ndash10)
alanine aminotransferase (alt) 2033 iUlitre (0ndash35)
alkaline phosphatase 987 iUlitre (71ndash234)
Gamma-glutamyl transferase (GGt) 870 iUlitre (0ndash51)
1 What is the name of this rash Choose ONE answer ONLY from the followingA Erythema multiformeB Erythema migransC GianottiminusCrosti syndromeD EczemaE Dermatitis herpetiformis
2 What is the most likely diagnosis Choose ONE Answer ONLY from the followingA Autoimmune hepatitisB Hepatitis BC Hepatitis DD Wilson diseaseE Alpha-1 antitrypsin deficiency
3 What is the best means of management Choose ONE answer ONLY from the followingA Isolation until the jaundice disappearsB ImmunosuppressionC Copper chelating agents and genetic counsellingD Patient and family education with consideration of
antiviral agentsE Liver transplantation
Case 3A 10-month-old boy presents with 3 weeks of vomiting and constipation ndash he is passing hard stools every 2ndash3 days He has fallen from the 9th to below the 04th centile in the last 6 weeks He passed meconium within the first 24 h of life On examina-tion he looks pale and there are some dysmorphic features ndash a short nose long philtrum and wide mouth He has normal heart sounds with a grade 3 ejection systolic murmur loudest at the upper right sternal edge Examination is otherwise normal
Initial investigations are as follows
haemoglobin 91 gdl (113ndash141)
total white blood cell count 124 times 109litre (60ndash170)
Platelet count 407 times 109litre (150ndash400)
sodium 144 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 78 mmollitre (25ndash75)
creatinine 78 μmollitre (45ndash120)
albumin 52 glitre (35ndash50)
corrected calcium 384 mmollitre (238ndash263)
Phosphate 167 mmollitre (099ndash157)
1 What is the most likely diagnosis Choose ONE answer ONLY from the followingA HyperparathyroidismB Acute leukaemiaC Williams syndromeD Hypervitaminosis DE Familial hypocalciuric hypercalcaemia
2 Which investigation would be most useful in establishing the diagnosis Choose ONE answer ONLY from the followingA Intact parathyroid hormone assayB Blood filmC Fluorescent in-situ hybridization for 7q1123 deletionD 25-hydroxyvitamin D assayE Urine calciumcreatinine ratio
3 Which of the following treatments would not be suitable for this patient Choose ONE answer ONLY from the followingA Low calcium dietB Normal saline infusionC FurosemideD CorticosteroidsE Bisphosphonates
Case 4A 10-week-old girl presents with a 2-day history of poor feed-ing Her mother has been concerned about weakness since birth She only has a flicker of movement in the arms none in the legs and has a weak cry She has been passing urine and opening her bowels normally She was born at full term by normal delivery and did not require any resuscitation at birth Normal fetal movements were felt antenatally and there was no polyhydramnios She is the first child of non- consanguineous parents and there is no significant family his-tory On examination she is alert and fixing and following appropriately She has a weak cry and a weak suck There is reduced central and peripheral tone with marked head lag
Figure 2 rash found on examination
Paediatrics and child health 184 203 copy 2008 elsevier ltd all rights reserved
self-assessment
Muscle power is grade 3 out of 5 in the arms and legs There is no muscle or tongue fasciculation and she has absent reflexes throughout The remainder of the examination is normal
Electromyogram shows irregular polyphasic motor unit potentials with marked instability consistent with a dener-vating and re-innervating process (Figure 3)
1 Which of the following additional investigations may be helpful Choose ONE answer ONLY from the followingA Nerve conduction studiesB Creatine kinase assayC Muscle biopsyD SMN1 gene analysisE All of the above
2 What is the most likely cause of this childrsquos symptoms Choose ONE answer ONLY from the followingA Congenital myotonic dystrophyB Duchenne muscular dystrophyC PraderminusWilli syndromeD Spinal muscular atrophyE Mitochondrial myopathy
3 What is the mode of inheritance of this disease Choose ONE answer ONLY from the followingA X-linked recessiveB Autosomal recessiveC Autosomal dominantD MitochondrialE Sporadic
Case 5A 13-year-old girl presents with a 3-week history of fever up to 40degC night sweats and headache She has a reduced appetite with some weight loss She has no other specific symptoms She was on holiday in China 7 months ago On examination she looks well and has a temperature of 387degC There is no lymphadenopathy and no rashes Examination is entirely normal
Results of investigations are as follows
haemoglobin 126 gdl (120ndash160)
total white blood cell count 132 times 109litre (43ndash108)
neutrophil count 115 times 109litre (25ndash75)
Platelet count 244 times 109litre (150ndash400)
Blood film neutrophilia with left shift
erythrocyte sedimentation rate 63 mmh (1ndash20)
c-reactive protein 219 mglitre (0ndash5)
Blood culture Streptococcus intermedius
from anaerobic bottle only
csf culture negative
Magnetic resonance imaging (MRI) of the brain shows acute frontal sinusitis with a large intracranial frontal extra-dural empyema (Figure 4)
1 Which of the following would be appropriate management Choose ONE answer ONLY from the followingA A 12-week course of intravenous antibioticsB Drainage of the frontal sinus followed by 2 weeks of
intravenous antibioticsC Drainage of the empyema followed by 2 weeks of
intravenous antibioticsD Drainage of the empyema and the frontal sinus
followed by 2 weeks of oral antibiotics
1151
1152
1153
1154
1155
1156
1157
1158
1159
1200
50ms 1mV
Figure 3 electromyogram recording from the patient Figure 4 Parasagittal section from mri scan of patient
Paediatrics and child health 184 204 copy 2008 elsevier ltd all rights reserved
self-assessment
E Drainage of the empyema and the frontal sinus followed by 8 weeks of intravenous antibiotics
2 Streptococcus intermedius is a potential pathogen in which of the following infections Choose ONE answer ONLY from the followingA Liver abscessB Urinary tract infectionC MeningitisD Thoracic empyemaE Pneumonia
3 Which of the following statements regarding lsquopyrexia of unknown originrsquo in children is false Choose ONE answer ONLY from the followingA Malignancy is the underlying pathology in 5ndash15 of
casesB An aetiology will be found in over 90 of casesC The most common cause is infectionD A rheumatological cause is found in 10ndash20 of casesE Familial Mediterranean fever can occur in children of
non-Mediterranean ethnicity
Answers
Case 11 AThe anion gap is a useful tool to differentiate the causes of a metabolic acidosis It is calculated by the equation
Anion gap = [Na K ] [Cl HCO ]3+ + minus minus+ minus +
It represents the effect of unmeasured anions on the plasma pH and is normally 10ndash18 mmollitre
2 CMicrovillus inclusion disease is a severe autosomal recessive enteropathy that is typically apparent within hours or days after birth It is the second most common cause of protracted diarrhoea in the newborn after infectious causes It is characterized by severe yellow watery diarrhoea and malabsorption due to hypoplasia andor atrophy of the villi of the small intestine secondary to an inherited defect in the brush border membrane This results in severe dehydration malnutrition and metabolic acidosis due to bicarbonate loss from the gut
3 CDiagnosis of microvillus inclusion disease is made on small bowel biopsy Electron microscopy findings are of intracellular brush border inclusions and densely packed apical cytoplasmic vesicular bodies indicating microvillous atrophy There is no cure Treatment is supportive with total parenteral nutrition and consideration of small bowel transplantation
Further reAding
Goulet O ruemmele f causes and management of intestinal failure
in children Gastroenterology 2006 130(suppl 1) s16ndash28
rhoads Jm Vogler rc lacey sr et al microvillus inclusion disease
In vitro jejunal electrolyte transport Gastroenterology 1991
100 811ndash817
Case 21 CGianottindashCrosti syndrome is a distinct self-limiting rash commonly associated with viral infections in children between 2 and 6 years of age It presents as multiple pink to redminusbrown papules or papulovesicles which may be pruritic and can become confluent Gianotti and Crosti initially described the exanthema as associated with hepatitis B virus and they termed it papular acrodermatitis of childhood It can occur in several viral diseases eg hepatitis A B and C coxsackie viruses and cytomegalovirus
2 BHepatitis is a syndrome characterized by inflammation or injury of liver cells which may develop into cell necrosis and subsequently fibrosis andor cirrhosis Biochemically there are raised liver enzymes The degree of transaminase elevation does not correlate with the severity of the disease process Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of viral hepatitis
3 DHepatitis B infection is transmitted via blood sexually or vertically Infection may be acute or chronic Diagnostic markers are the presence of surface antigen (HBsAg) and HBV DNA The presence of e antigen (HBeAg) indicates high infectivity Infected newborns have a 95 risk of becoming carriers this risk decreases with infection acquired later in childhood Approximately 15ndash25 of HBV carriers will die from cirrhosis or hepatocellular carcinoma Extrahepatic findings are more common in older children and include membranous glomerulonephritis and GianottiminusCrosti syndrome Fulminant hepatic failure occurs in severe cases resulting in persistent jaundice encephalopathy and coagulopathy Management includes counselling family members monitoring for ongoing liver disease and consideration of antiviral therapy
Further reAding
Brandt O abeck d Gianotti r Burgdorf W Gianotti crosti
syndrome J Am Acad Dermatol 2006 54 136ndash145
slowik mK Jhaveri r hepatitis B and c viruses in infants and
young children Semin Pediatr Infect Dis 2005 16 296ndash305
Case 31 CHypercalcaemia is uncommon in infancy The most common symptoms in this age group are irritability vomiting and constipation It may be a manifestation of Williams syndrome vitamin D or calcium excess as well as disorders associated with reduced bone formation such as hypophosphatasia or increased bone resorption such as malignancy Occasionally
Paediatrics and child health 184 205 copy 2008 elsevier ltd all rights reserved
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-
SympoSium neonatology
Common causes of acidndashbase imbalances
pH PCO2 H2CO3 Base excess Common neonatal causes
Respiratory acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
uarr normal normal bull upper airway obstruction choanal atresia
pierre-Robin sequence
bull lung abnormalities respiratory distress
syndrome transient tachypneoa of
newborn pneumonia meconium aspiration
syndrome pulmonary hypoplasia
congenital pulmonary malformations
bull Central hypoventilation hypoxic-ischaemic
encephalopathy intracranial haemorrhage
bull neuromuscular insufficiency congenital
myopathies congenital neuropathies
bull iatrogenic inadequate ventilatory settings
Compensated lower limit
of normal
uarr uarr gt+3
metabolic acidosis Uncompensated lt 730
(normal lower pH range
73ndash735)
normal darr ltminus3 increased anion gap
bull lactic acidosis sepsis hypoperfusion
shock necrotizing enterocolitis
bull inorganic acidosis inborn errors of
metabolism renal failure
normal anion gap
bull increased gastrointestinal H2Co3 losses
ileostomy diarrhoea
bull Renal tubular acidoses
Compensated lower limit
of normal
darr darr ltminus3
Respiratory alkalosis Uncompensated gt 745 darr normal normal bull iatrogenic excessive ventilatory settings
bull Compensatory hyperventilation hypoxic-
ischaemic encephalopathy
Compensated higher limit
of normal
darr darr ltminus3
metabolic alkalosis Uncompensated gt 745 normal uarr gt+3 bull gastric losses vomiting non-replacement
of excessive nasogastric aspirates
bull thiazide and loop diuretics
bull Hypokalaemia
Compensated higher limit
of normal
uarr uarr gt+3
Table 1
Metabolic acidosisThis frequently affects infants in the neonatal unit and has many causes1011 (see Table 1) There may be overproduction of tissue acid impaired acid clearance gastrointestinal loss of bicarbonate or an exogenous increased acid load eg chloride total paren-teral nutrition (TPN) or albumin1ndash323
Calculation of the anion gap to distinguish an increased anion gap acidosis from a non-anion gap acidosis is important both for treatment and prognosis1011 Acidosis stimulates respiratory compensation but this is limited in unstable infants Similarly renal compensation with improved HCO3
minus conservation is con-strained by tubular immaturity Treatment of the acidosis should be directed at the underlying cause eg hypoxia hypotension or excess Clminus rather than by administration of base
Metabolic alkalosisThis is unusual in neonates and is most frequently seen in infants with chronic lung disease or heart failure who are receiving diuretics Diuretics cause alkalosis by increasing renal fluid and Na+ losses An active process to reabsorb Na+ occurs in tubule cells which through enhanced H+ secretion and HCO3
minus reab-sorption produce alkalosis27
paeDiatRiCS anD CHilD HealtH 184 17
Metabolic alkalosis may also occur with excessive loss of gas-tric contents eg protracted vomiting or inadequate replacement of nasogastric aspirates (see Table 1)
Interpreting blood gases
Blood gas measurements can provide important diagnostic and prognostic information and a systematic approach to blood gas analysis is described in Table 2 The clinical management of infants with abnormal gases requires a good understanding of acidndashbase physiology and tissue oxygenation and an apprecia-tion of factors which may affect the reliability of samples
Arterial blood sampling is the gold standard however indwelling arterial catheters and arterial stab samples are usually restricted to infants who are critically ill or those who require sig-nificant ongoing intervention Gases are most frequently measured in capillary or venous samples which correlate well with arterial samples for PaCO2 pH and base excess in babies and children receiving intensive care These correlations however are not valid in infants with peripheral vasoconstriction and hypotension2324
Non-invasive monitoring techniques may enable us to reduce the frequency of blood gas sampling Transcutaneous monitoring
5 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
A systematic approach to blood gas analysis
1 Collect the relevant information
bull type of gas ndash capillary or arterial
bull Current respiratory support ndash document level
bull transcutaneous Co2 and Sao2 levels
bull Clarify no significant clinical events before sampling
2 pH accept a range between 730 and 745 in newborn
babies this is lower than in older children is there an
alkalosis (pH gt 745) or an acidosis (lt 730)
3 Co2 aim for a range between 45 and 65 kpa a paCo2 level
more than 65 kpa suggests inadequate alveolar ventilation
while less than 45 kpa suggests hyperventilation Correlate
values with non-invasive measures
4 o2 Can only be assessed from arterial gases aim for pao2
between 60 and 80 kpa Correlate results with pulse
oximetry levels
5 HCo3 and base excess normal HCo3 level is between 20 and
24 mmollitre and bases excess +3 to minus3
6 anion gap look at the anion gap and lactate to help identify
the cause of an acidosis normal lactate levels should be less
than 2 mmollitre
7 Respiratory or metabolic compensation look at the pH and
assess whether it is appropriate for the Co2 level or is there
evidence of compensation
8 interpret use both the clinical history and blood gas
findings to help you identify the primary problem aim your
management at treating the underlying cause
9 Reassess if clinical management changes have been made
repeat the blood gas after an appropriate time interval to
ensure improvement
Table 2
provides a highly accurate and reliable method for measuring PaCO2 through the skin it can however be technically difficult may cause tissue damage and is of limited reliability when peripheral perfusion is reduced25 Continuous end-tidal CO2 measurements correlate well with arterial CO2 values in patients with normal ventilation and perfusion however in babies with lung disease alveolar collapse small tidal volumes and rapid respiratory rates can make these measurements unreliable26 Despite its limitations transcutaneous monitoring provides the best method for CO2 trend monitoring in the neonatal intensive care unit (NICU)25
Oxygen saturation levels can be continuously measured non-invasively using pulse oximetry While oximetry is easy to perform and accurate on occasion SaO2 levels obtained may be unreliable when tissue perfusion is poor or with movement artefact SaO2 monitoring is highly sensitive at detecting hypoxia but is limited in detecting hyperoxia as at levels more than 90 small changes in SaO2 may result in unacceptably large increases in PaO227 It is therefore essential that SaO2 alarm limits are set for all neonates receiving respiratory support to detect hypoxia and prevent hyperoxia1627
Continuous non-invasive monitoring provides invaluable information when managing complex infants in the NICU but it does not replace the need for regular blood gas analysis
paeDiatRiCS anD CHilD HealtH 184 17
ReFeRenCeS
1 Kellum Ja Determinants of blood pH in health and disease
Crit Care 2000 4 6ndash14
2 Quigley R Baum m neonatal acid base balance and disturbances
Semin Perinatol 2004 28 97ndash102
3 Brouillette Rt Waxman DH evaluation of the newbornrsquos blood gas
status Clin Chem 1997 43 215ndash221
4 Chan JC acid-base disorders and the kidney Adv Pediatr 1983 30
401ndash471
5 Siggaard-andersen o the pH-log pCo2 blood acidndashbase nomogram
revised Scand J Lab Invest 1962 14 598ndash604
6 Saetta m mortola Jp interaction of hypoxic and hypercapnic stimuli
on breathing pattern in the newborn rat J Appl Physiol 1987 62
506ndash512
7 Baum m Quigley R postnatal renal development in Seldin DW
giebisch g eds the kidney physiology and pathophysiology new
york lippincott Williams and Wilkins 2000 p 703ndash726
8 ortiz la Quan a Weinberg a et al effect of prenatal
dexamethasone on rat renal development Kidney Int 2001 59
1663ndash1669
9 gabow pa Kaehny WD Fennessey pV goodman Si gross pa
Schrier RW Diagnostic importance of an increased serum anion gap
N Engl J Med 1980 303 854ndash858
10 lorenz Jm Kleinman li markarian K oliver m Fernandez J Serum
anion gap in the differential diagnosis of metabolic acidosis in
critically ill newborns J Pediatr 1999 135 751ndash755
11 Deshpande Sa platt mp association between blood lactate and
acid-base status and mortality in ventilated babies Arch Dis Child
1997 76 F15ndash20
12 Stewart pa modern quantitative acid-base chemistry Can J Physiol
Pharmacol 1983 61 1444ndash1461
13 Dakshinamurti S pathophysiologic mechanisms of persistent
pulmonary hypertension of the newborn Pediatr Pulmonol 2005
39 492ndash503
14 mourani pm ivy DD gao D abman SH pulmonary vascular
effects of inhaled nitric oxide and oxygen tension in
bronchopulmonary dysplasia Am J Respir Crit Care Med 2004
170 1006ndash1013
15 Deulofeut R Critz a adams-Chapman i Sola a avoiding hyperoxia
in infants le 1250 g is associated with improved short- and long-
term outcomes J Perinatol 2006 26 700ndash705
16 Chow lC Wright KW Sola a Can changes in clinical practice
decrease the incidence of severe retinopathy of prematurity in very
low birth weight infants Pediatrics 2003 111 339ndash345
17 Boylan gB young K panerai RB Rennie Jm evans DH Dynamic
cerebral autoregulation in sick newborn infants Pediatr Res 2000
48 12ndash17
18 Kaiser JR gauss CH pont mm Williams DK Hypercapnia during
the first 3 days of life is associated with severe intraventricular
hemorrhage in very low birth weight infants J Perinatol 2006 26
279ndash285
19 Fabres J Carlo Wa phillips V Howard g ambalavanan n Both
extremes of arterial carbon dioxide pressure and the magnitude of
fluctuations in arterial carbon dioxide pressure are associated with
severe intraventricular hemorrhage in preterm infants Pediatrics
2007 119 299ndash305
20 thome uH Carroll W Wu tJ et al outcome of extremely preterm
infants randomized at birth to different paCo2 targets during the
first seven days of life Biol Neonate 2006 90 218ndash225
6 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
21 Carlo Wa Stark aR Wright ll et al minimal ventilation to prevent
bronchopulmonary dysplasia in extremely-low-birth-weight infants
J Pediatr 2002 141 370ndash374
22 okumura a Hayakawa F Kato t et al Hypocarbia in preterm
infants with periventricular leukomalacia the relation between
hypocarbia and mechanical ventilation Pediatrics 2001 107
469ndash475
23 peters o Ryan S matthew l Cheng K lunn J Randomised
controlled trial of acetate in preterm neonates receiving parenteral
nutrition Arch Dis Child 1997 77 F12ndash15
24 yildizda D yapiciolu H yilmaz Hl Sertdemir y Correlation of
simultaneously obtained capillary venous and arterial blood gases
of patients in a paediatric intensive care unit Arch Dis Child 2004
89 176ndash180
25 aliwalas ll noble l nesbitt K et al agreement of carbon
dioxide levels measured by arterial transcutaneous and end tidal
methods in preterm infants 28 weeks gestation J Perinatol 2005
25 26ndash29
26 Hagerty JJ Kleinman me Zurakowski D et al accuracy of a new
low-flow sidestream capnography technology in newborns a pilot
study J Perinatol 2002 22 219ndash225
paeDiatRiCS anD CHilD HealtH 184 17
27 poets CF Wilken m Seidenberg J Southall Dp von der Hardt H
Reliability of a pulse oximeter in the detection of hyperoxemia
J Pediatr 1993 122 87ndash90
Practice points
bull a stable extracellular pH is important for optimal cellular
functioning
bull abnormalities in acidndashbase balance are regulated by buffer
systems and the respiratory and renal tract
bull maintaining a stable pH is challenging for newborn babies
due to their high rates of acid production and immature
regulatory mechanisms
bull arterial or capillary blood gases provide an effective way to
monitor acidndashbase balance in newborns
bull Blood gases should be analysed in a structured manner
assessing pH and then respiratory and metabolic components
bull the treatment of acidndashbase abnormalities should be directed
at the underlying problem not merely at correcting pH
7 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Recognition and management of neonatal seizuresmalcolm levene
AbstractSeizures are the most common major manifestation of central nervous
system dysfunction in the newborn there are many causes but perina-
tal asphyxia and haemorrhagicinfarction lesions account for about 75
there is now considerable evidence that frequent but short seizures in
the neonate affect subsequent neurodevelopmental outcome Studies
using eeg or modified continuous tracing of eeg activity (aeeg or CFm)
have shown that there is often electroconvulsive dissociation this re-
fers to poor correlation between electrical seizures and clinical seizures
Commonly used anticonvulsants appear to increase electroconvulsive
dissociation effective management of neonatal seizures has proved very
disappointing and less than 50 of seizures are abolished by first-line
anticonvulsant medication (phenobarbitone or phenytoin) Drugs such
as midazolam and lidocaine may further reduce seizures but require
more evaluation the challenge is to assess new and more effective anti-
convulsants which are themselves associated with little neurotoxicity
Keywords antiepileptic drugs eeg neonatal seizures neurodegeneration
Convulsions are the most common major neurological sign seen in newborn infants and their incidence estimated from large population studies is 26 per 1000 live births1 Premature infants are over four times more likely to have convulsions than full-term infants12 Neonatal status epilepticus (continuous seizure activity lasting 30 min or more) diagnosed clinically is rare and accounts for only 5 of infants with seizures1 although this is now recognized more frequently as the result of continuous EEG monitoring3
Neonatal convulsions are described as presenting in a num-ber of different ways and various seizure types can be seen in the same baby over a number of hours The frequencies of the various patterns of seizure activity are given in Table 1 In very premature babies and to a lesser extent in term infants minor movement abnormalities may be difficult to identify as subtle seizures These include lip smacking tongue thrusting mouth-ing pedalling type movements of the lower limbs or swimming movements of the arms Apnoea can be a common manifesta-tion of subtle seizures The signs can be protean and vary from baby to baby or even in the same baby Virtually any stereotypic
Malcolm Levene MD FMedSc FRCPCH FRCH is Professor and Head of
Department of Paediatrics and Child Health at University of Leeds Leeds
and Honorary Neonatologist at Leeds General Infirmary Leeds UK
paeDiatRiCS anD CHilD HealtH 184 178
movement may be a manifestation of a seizure disorder in the newborn
Aetiology
The more carefully the fitting baby is investigated the more likely it is that a cause for the seizures will be found A number of recent papers have described the aetiology of neonatal con-vulsions after extensive investigations14 Tekgul et al4 recently studied a consecutive group of full-term infants with evidence of neonatal convulsions (recognized both clinically and on EEG) and reported their outcome Table 2 summarizes these data as well as risk of moderate or severe disability for each causative factor Perinatal asphyxia is the commonest cause for convul-sions in term infants with haemorrhagic or ischaemic lesions also being common
Overall the prognosis for the group of term babies with con-vulsions was good 72 had a favourable outcome Where asphyxia (hypoxicndashischaemic insult) is the cause of neonatal convulsions the outcome is poor in 50 The prognosis for neonatal convulsions when they were due to arterial or cere-brovenous infarction or intracranial haemorrhage was generally good Individually inborn errors are a very rare cause of neo-natal convulsions but in view of the treatable nature of some of these it is essential that these be considered and investigated appropriately5
Patterns of seizure activity in the newborn
Movement pattern Frequency ()
Clonic 50
tonic 20
Subtle 10ndash35 depending on maturity
myoclonic 5
Table 1
Cause incidence and outcome of neonatal convulsions in term infants14
Aetiological factor Incidence () Poor outcome ()
asphyxia 38ndash40 50
Cerebral arteriovenous
infarction
20 0
intracranial haemorrhage 12ndash20 13
Congenital cerebral anomaly 5ndash10 100
Hypoglycaemiahypocalcaemia 3ndash19
infection 3ndash20
inborn error of metabolism 1
unknown cause 10ndash13 0
Refers to moderate and severe neurodevelopmental abnormalitynumbers too small to make meaningful predictions
Table 2
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Controversies in the clinical management of neonatal seizures
In recent years we have learnt much more about the neurobi-ology of seizures and their effect on the developing brain The neonatal brain is in a neurophysiologically hyperexcitable state compared to the more mature brain and therefore is more prone to seizure activity This is due largely to a relative excess of GABA neuroreceptors GABA receptors are usually inhibitory but in the immature brain they have a paradoxically excitatory effect This changes at about term in primates and with progressive develop-ment they adopt a neuroinhibitory role6
The propensity to seizures in the neonatal brain makes resolv-ing the balance of risks between continuing seizure activity on the one hand against potentially adverse effects of therapy on the other a very important equation Added to this is the problem of accurately diagnosing neonatal seizures and whether commonly used anticonvulsants are successful in controlling them
These conundrums can be posed as a series of challenging questions which are discussed below
Do neonatal convulsions cause brain injuryConvulsions are a sign of neurological compromise and may indi-cate significant underlying structural brain damage or biochemi-cal disturbance which may cause further brain damage in its own right There has been considerable debate about the scale of the disability that convulsions cause the immature brain over and above that due to the underlying cause Most of our knowledge comes from studies in rodents and these have provided some tentative answers to this question
Seizures in the mature brain lead to neuronal necrosis but studies in very young rat pups whose brain development is somewhat similar to full-term infants have shown that a series of five brief seizures on five successive days does not cause struc-tural neuronal damage but does produce morphological changes in hippocampal neurones and worryingly deficits in the rat learning and visual spatial memory function in adolescent and adult life7 A single prolonged neonatal convulsion in similarly immature rats does not produce any functional effects8 Others have shown that following priming of the neonatal rat brain by short seizures as described above a further insult comprising induction of status epilepticus in the same rats at an older age causes neuronal necrosis9 This has been referred to as the lsquotwo hit hypothesisrsquo10
A more specific question is does seizure activity in an already significantly compromised brain cause additional neuropathol-ogy Wirrell et al11 studied a series of immature rat pups with the induction of an hypoxicndashischaemic (asphyxial) insult fol-lowed by either chemically-induced fits or a control sham pro-cedure In the more severely asphyxiated animals the degree of brain damage was increased significantly in those that had the additional burden of induced seizures
In summary these studies show that the immature brain is more resistant to short frequent post-seizure damage than the mature brain but despite resulting in no loss of neuronal numbers the function of the brain is permanently affected in later life In the asphyxiated brain seizures appear to have an additional adverse effect on brain damage Furthermore the immature brain that has been lsquoprimedrsquo by early seizures is more
paeDiatRiCS anD CHilD HealtH 184 179
vulnerable to status epilepticus later in life It would appear from these data that frequent seizures in the human infant should be stopped and this begs the question as to whether currently used anticonvulsants effectively control neonatal seizures
Can we rely on clinical versus EEG diagnosis of neonatal convulsionsTraditionally the diagnosis of neonatal convulsions has been made by observation and description of the frequency of abnor-mal movements EEG has been technically difficult in the hostile electrical activity of a neonatal intensive care environment and considerable expertise is required for analysis of the trace It is usually not practical to undertake traditional EEG recordings at the time the baby shows abnormal movements More recently various technological developments have allowed more direct investigation of neuronal electrical activity by either video-EEG or compressed recording of the amplitude integrated EEG (aEEG or CFM)
Rennie et al3 at Kingrsquos College Hospital London have under-taken extensive evaluation of video-EEG and have found that this technique detects many convulsions not recognized by a single channel aEEG or CFM trace Of 19 infants with evidence of convulsions on EEG only four were recognized on CFM but this may have been due to the observersrsquo lack of experi-ence with this technique In other centres that have developed appropriate expertise aEEG or CFM has proved more sensitive to the detection of seizures Video-EEG studies have also shown that many movements interpreted by experienced clinicians to be seizures are not associated with abnormal cortical activity Conversely many electrical seizures are not associated with abnormal movements This is referred to as electroconvulsive dissociation
In summary clinical observation alone to detect the fitting baby is unreliable in that it may either over-detect seizure activ-ity which is not present on EEG or under-detect clinical seizures in infants with EEG-proven convulsions The decision as to which babies to treat with antiepileptic drugs therefore becomes somewhat arbitrary
Do anticonvulsants stop neonatal seizuresAlthough neonatal seizures are common there are few random-ized controlled trials assessing the benefits of antiepileptic drugs (AEDs) in the treatment of this condition Phenobarbitone is the most widely used first-line AED and in an Australasian study 95 of neonatologists and paediatric neurologists used this drug as first-line management12 The most commonly used loading dosage is 20 mgkg but regimens of up to 40 mgkg have been recommended (Table 3)13 Four trials have evaluated the effect of phenobarbitone in abolishing neonatal seizures Two of these studies used EEG to monitor response to the drug1415 and one compared phenobarbitone with phenytoin15 In the latter study seizures were completely controlled in only 43 of babies and in the group where phenytoin was the first drug used com-plete seizure control was achieved in 45 This study switched babies from their first AED to the other if complete control was not obtained on EEG monitoring after exposure to first-line therapy In babies who had been given phenobarbitone as first-line therapy seizure control was only achieved in 57 after phenytoin was added In those given phenytoin first complete
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Dosage regimens for first- second- and third-line anticonvulsants in the neonatal period
Loading dose Second loading dose if first
unsuccessfulMaintenance dose
phenobarbitone 20 mgkg by slow iv injection 10 mgkg iv 25ndash5 mgkg od
phenytoin 20 mgkg iv over 20 min not recommended
midazolam 150ndash200 μgkg iv infusion 1 μgkgmin iv infusion increasing to 5 μgkgmin
until favourable response
lidocaine 2 mgkg iv over 10 min 6 mgkgh for 6 h iv then 4 mgkgh for 12 h then
2 mgkgh for 12 h
lorazepam 005ndash01 mgkg by slow iv injection
Diazepam 03ndash04 mgkg iv over 3ndash5 min
lidocaine should not be used if the infant has previously been treated with phenytoin
Table 3
seizure control was achieved with the adding of phenobarbitone in 62
Boylan et al14 assessed the efficacy of phenobarbitone (20ndash40 mgkg iv over 20 min) in 14 babies monitored by video-EEG in only four was there complete abolition of seizures and in the other 10 electroconvulsive seizure activity increased whereas clinical evidence of seizures reduced This has been termed elec-troclinical dissociation and anticonvulsant drug use in the new-born appears to increase this feature They also showed that the babies least likely to respond to the first-line AED are those with the most abnormal background EEG
Two studies have evaluated the use of phenobarbitone in babies who had sustained significant asphyxial insult at birth Hall et al13 compared high-dose phenobarbitone (mean 39 mgkg) versus standard dose (27 mgkg) and reported fewer convul-sions and a significant reduction of severe disability or death in the high dose group (RR 030 CI 010ndash093) A recent study from India16 of babies with hypoxicndashischaemic encephalopathy ran-domized 25 babies to phenobarbitone (20 mgkg loading dose) and compared them with 20 control babies Only 2 of 25 (4) in the phenobarbitone group developed convulsions compared with 8 of 20 (40) in the control group (p = 001) Because of the specific enrolment criteria (asphyxial insult) neither of these studies is strictly comparable to the studies by Painter et al15 and Boylan et al14 whose intention was to assess the efficacy of first-line anticonvulsant therapy on convulsions of any cause diagnosed either clinically or by EEG
Other anticonvulsants used as second- and third-line drugs have been subject to few studies in the newborn Midazolam is administered as a bolus followed by continuous infusion A recent study17 has shown that in 10 of 13 neonates given intravenous midazolam for status epilepticus control of electri-cal seizures was achieved within the first hour of treatment having been previously shown to be refractory to phenobarbi-tone treatment Some of these babies required a second bolus infusion of midazolam to obtain control of all electrographic seizures
In some parts of Europe lidocaine is used as a third-line anti-convulsant Malingre et al18 evaluated 20 infants refractory to
paeDiatRiCS anD CHilD HealtH 184 180
both phenobarbitone and midazolam and who were then given lidocaine by continuous infusion Lidocaine was effective in abolishing electroconvulsive seizures diagnosed by aEEG in 76 of the treatment courses studied No babies developed cardiac arrhythmias a previously reported complication of lidocaine in older patients As a result of pharmacokinetic studies the dosage regimen has been modified (see Table 3)
In summary phenobarbitone is effective in seizure control in less than 50 of babies and even when combined with phe-nytoin the efficacy of these drugs together remains poor More worrying is the observation that phenobarbitone tends to reduce clinically evident seizures thereby giving the clinician a false sense of security whilst having little or no effect on the num-bers of electroconvulsive disorders This has been summarized appropriately as lsquoafter all these years we still love what doesnrsquot workrsquo19 Both midazolam and lidocaine infusions appear to be effective in abolishing severe seizures in some infants resistant to phenobarbitone Lidocaine should not be given to babies previ-ously exposed to phenytoin for fear of a synergistic adverse effect on cardiac rhythm
Do antiepileptic drugs cause brain damageA riskndashbenefit analysis is needed to evaluate the efficacy of anticonvulsants in stopping neonatal seizures which is poor with standard anticonvulsants as discussed above against the risk of administering the anticonvulsant drugs themselves Phenobarbitone has been reported to have adverse effects on the developing brain including inhibition of brain growth20 neuronal toxicity21 and adverse behavioural and cognitive effects into adult life when administered to young animals22 Phenytoin shows unpredictable plasma levels and potential cardiotoxicity
Recent studies have shown an effect of AED exposure on the developing brain by causing neurodegeneration23 Phenytoin administration to immature rat pups at doses which produce serum levels similar to those achieved in human neonates was associated with widespread neuronal death as a result of apop-tosis (programmed cell death) Phenobarbitone had a similar effect when a dosage regimen similar to 40 mgkg was used and
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
this effect was maximal in the more immature brain Diazepam and clonazepam also resulted in a similar effect Midazolam and lidocaine were not tested in this study The combination of phenobarbitone or phenytoin with diazepam had a particularly profound effect on neurodegeneration
In summary recent data suggest that the commonly used AEDs for neonatal convulsions may in themselves cause neuro-degeneration due to apoptosis with lasting effects on develop-ment Many babies with neonatal convulsions are treated with at least two AEDs and this may produce more severe adverse effects than the seizures themselves
Practical management of neonatal seizures
Assimilation of these data and formulation of a rational policy is difficult when faced with a fitting neonate on an intensive care unit and pressure on the medical staff to lsquodo somethingrsquo but it is important to accept that sometimes doing nothing is preferable to using potentially dangerous drugs in a situation which does not warrant such intervention Many babies who have normal interseizure neurological clinical findings and whose seizures are relatively brief and infrequent probably do not need anticon-vulsant medication A normal or near-normal background EEG trace should reassure the clinician that anticonvulsants can be withheld
Some causes of neonatal convulsions are treatable such as meningitis hypoglycaemia hypocalcaemia and inborn errors of metabolism and each baby should be rapidly and carefully investigated for cause of the convulsions
In some babies clinical assessment of seizures is difficult ie when the baby is very sick small or paralyzed Sometimes it may be difficult to assess the significance of certain movement pat-terns Under these circumstances an EEG may prove to be very helpful In many units EEG is not available out of hours and a simple aEEG or CFM is strongly advised Modern instruments are very simple to apply and prolonged or frequent seizures should be identified with only moderate training The printout can be faxed to a more senior doctor if there is doubt as to what is shown on the trace
The balance of knowledge now is that frequent seizures cause additional damage to the developing brain and that treatment to abolish the seizures is warranted Unfortunately there is little evidence that the majority of seizures can be effectively termi-nated by current standard therapy Furthermore it appears that the more abnormal the background EEG the more difficult it is to control the seizures Nevertheless a written protocol for the management of neonatal convulsions is required on each unit Phenobarbitone and phenytoin remain the mainstay of treat-ment although their effectiveness is disappointing There is little to suggest that midazolam is more effective than lidocaine as third-line therapy but lidocaine is precluded if phenytoin has been previously used
In view of the anxiety as to the neurodegenerative effects on the immature brain of most anticonvulsants used in the neonatal period (particularly when multiple drugs are used) it is prefer-able to use only one drug to maximum dosage before introduc-ing a second In addition the duration of anticonvulsants should be minimized and the drugs stopped at the earliest opportu-nity It is my practice to stop anticonvulsants prior to discharge
paeDiatRiCS anD CHilD HealtH 184 18
from hospital if the baby is neurologically normal on clinical examination
REFEREnCES
1 Ronen gm penney S andrews W the epidemiology of clinical
neonatal seizures in newfoundland a population-based study
J Pediatr 1999 134 71ndash75
2 lanska mJ lanska DJ Baumann RJ et al a population-based study
of neonatal seizures in Fayette County Kentucky Neurology 1995
45 724ndash732
3 Rennie Jm Chorley g Boylan gB et al non-expert use of the
cerebral function monitor for neonatal seizure detection Arch Dis
Child Fetal Neonatal Ed 2004 89 F37ndashF40
4 tekgul H gauvreau K Soul J et al the current etoliologic profile
and neurodevelopmental outcome of seizures in term newborn
infants Pediatrics 2006 117 1270ndash1280
5 Surtees R Wolf n treatable neonatal epilepsy Arch Dis Child 2007
92 659ndash661
6 Ben-ari y Holmes gl effects of seizures on developmental
processes in the immature brain Lancet Neurol 2006 5 1055ndash
1063
7 Holmes gl gairsa Jl Chevassus-au-louis n et al Consequences of
neonatal seizures in the rat morphological and behavioral effects
Ann Neurol 1998 44 845ndash857
8 Stafstrom Ce Chronopoulos a thurber S et al age-dependent
cognitive and behavioural deficits following kainic-acid inducing
seizures Epilepsia 1993 34 420ndash432
9 Schmid R tandon p Stafstrom Ce et al effects of neonatal seizures
on subsequent seizure-induced brain injury Neurology 1999 53
1754ndash1761
10 Hoffmann aF Zhao Q Holmes gl Cognitive impairment following
status epilepticus and recurrent seizures during early development
support for the ldquotwo-hit hypothesisrdquo Epilepsy Behav 2004 5
873ndash877
11 Wirrell eC armstrong ea osman lD et al prolonged seizures
exacerbate perinatal hypoxic-ischemic brain damage Pediatr Res
2001 50 445ndash454
12 Carmo KB Barr p Drug treatment of neonatal seizures by
neonatologists and paediatric neurologists J Paediatr Child Health
2005 41 313ndash316
13 Hall Rt Hall FK Daily DK High-dose phenobarbital therapy in term
newborn infants with severe perinatal asphyxia a randomized
prospective study with three-year follow-up J Pediatr 1998 132
345ndash348
14 Boylan gB Rennie Jm pressler Rm et al phenobarbitone neonatal
seizures and video-eeg Arch Dis Child Fetal Neonatal Ed 2002 86
F165ndash170
15 painter mJ Scher mS Stein aD et al phenobarbital compared with
phenytoin for the treatment of neonatal seizures N Engl J Med
1999 341 485ndash489
16 Singh D Kumar p narang a a randomized controlled trial of
phenobarbital in neonates with hypoxic ischemic encephalopathy
J Matern Fetal Neonatal Med 2005 18 391ndash395
17 Castro Conde JR Borges H Domenech martinez e et al midazolam
in neonatal seizures with no response to phenobarbital Neurology
2005 64 876ndash879
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
18 malingre mm Van Rooij lgm Rademaker Cma et al Development
of an optimal lidocaine infusion strategy for neonatal seizures Eur
J Pediatr 2006 165 598ndash604
19 Sankar R painter mJ neonatal seizures after all these years we still
love what doesnrsquot work Neurology 2005 64 776ndash777
20 Diaz J Schain J Bailey Bg phenobarbital-induced brain growth
retardation in artificially reared rat pups Biol Neonate 1977 32 77ndash82
21 mattson RH phenobarbital toxicity in levy RH Dreifuss Fe
mattson RH et al eds antiepipeptic Drugs 3rd edn new york
Raven 1985 p 341ndash355
22 mikati ma Holmes gl Chronopoulos a et al phenobarbital
modifies seizure-related brain injury in the developing brain Ann
Neurol 1994 36 425ndash453
23 Bittigau p Sifringer m genz K et al antiepileptic drugs and
apoptotic neurodegeneration in the developing brain Proc Natl
Acad Sci U S A 2002 99 15089ndash15094
paeDiatRiCS anD CHilD HealtH 184 182
Practice points
bull the clinician needs to be aware that almost any repetitive
stereotype movement pattern can be a manifestation of
neonatal seizures
bull eeg is important in defining neonatal seizures
bull Frequent short-lived seizures have been shown to cause long-
term neurodevelopmental problems
bull Conventional anticonvulsant medication is ineffective in
abolishing neonatal seizures in greater than 50 of cases
bull there is evidence that exposure of the neonatal brain to
multiple anticonvulsants causes neuronal death
bull Future research is needed to evaluate more effective
anticonvulsants for treating this condition
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
Emotional support for families of sick neonatesMarina nicolaou
cristine Glazebrook
AbstractParents of sick neonates experience high levels of stress anxiety and
depression Most interventions with families of sick infants have focused
on fostering the motherndashinfant relationship through the provision of
information about infant developmental needs or through increased
motherndashinfant contact Many of these studies have reported improved
maternal well-being though there are some concerns about the scope
and practicality of large-scale interventions The few studies to have
prioritized emotional support for parents of sick neonates have pro-
duced encouraging results even interventions requiring relatively few re-
sources such as telephone support parent-to-parent support and group
support have been associated with reduced psychological morbidity for
parents The needs of parents can change throughout their infantrsquos hos-
pitalization and not all want or benefit from the provision of additional
support Thus neonatal intensive care units should aim to provide a
varied flexible and sustainable programme of support options Further
research should focus on the needs of fathers
Keywords mental health neonatal intensive care parents
The admission of an infant to neonatal care is acknowledged to be a source of considerable distress for families This review aims to explore evidence for the psychological impact on families of having an infant in neonatal intensive care and to identify evi-dence for the effectiveness of interventions to promote parental well-being It will conclude with recommendations for strategies to support parents of vulnerable infants and suggestions for fur-ther research
Psychological impact of neonatal care for parents
The majority of research examining the effect on parents of having a sick neonate has focused on families of premature or low birthweight infants Such research has found that parents with a sick neonate exhibit high levels of stress compared to normative samples and to parents of healthy full-term infants1 Singer et al2 examined the stress experienced by mothers of high-risk very low birthweight (VLBW) low-risk VLBW and term
Marina Nicolaou MPhil is a Teaching Assistant at the School of
Community Health Sciences University of Nottingham Nottingham UK
Cristine Glazebrook PhD is a Professor of Health Psychology at the School
of Community Health Sciences University of Nottingham Nottingham UK
PaeDiaTrics anD cHilD HealTH 184 196
infants Several self-report measures were used including the Brief Symptom Inventory the Parenting Stress Index (PSI) the Impact on Family Scale and the Family Inventory of Life Events and Changes (FILE) Mothers of VLBW infants had more psycho-logical distress at 1 month compared to mothers of term infants Mothers of high-risk VLBW infants also reported high psycho-logical distress at 2 years and high levels of parenting stress at 3 years Mothers have also been found to have higher stress levels compared to fathers Shaw et al3 examined the prevalence of acute stress disorder (ASD) in 40 parents whose infants were in the neonatal intensive care unit (NICU) Nearly half of the moth-ers (44) met the criteria for ASD although none of the fathers did Furthermore the severity of the symptoms (measured by the number of concurrent symptoms) was greater for the moth-ers than for the fathers3 The reasons behind this difference have been widely speculated with some believing that it is due to the mothersrsquo greater psychological involvement with the infant as evidenced by their general greater vulnerability to postpartum psychological disorder It could also reflect gender differences in coping style
Having an infant who requires intensive medical care repre-sents a significant emotional burden for families Not only is there extreme anxiety surrounding the infantrsquos health and distress for the childrsquos suffering there is also the unfamiliar and intimidating environment of the NICU to adjust to Hopper in her review of the literature identified sources of stress for parents of sick neo-nates as falling into three areas4 Situational factors included the severity of the infantrsquos illness and how parents adapted to the life crisis of having a sick infant Personal factors involved parental emotions about their roles and the instrumental and informa-tional support which were available to them The third area was classified as environmental sources of stress and included the environment of the NICU and the relationship between parents and members of staff This relationship has been examined by several studies in the nursing literature nurses are seen as ide-ally placed to provide the necessary support and information to parents with sick neonates However whilst some studies have shown that supportive and helpful hospital staff can have a posi-tive effect on parents other studies have highlighted the prob-lems and difficulties which can manifest It has been shown that parents and nurses often have very different ideas about issues eg the necessary skills and competencies needed in an NICU or the characteristics that make a lsquogood motherrsquo
Research has shown that there may be a relationship between high levels of parental stress and an increased likelihood of depression5 Postpartum depression is a psychiatric illness which appears in 10ndash15 of postpartum women Its reported preva-lence rates however have ranged from less than 10 up to 306 depending on the instruments used the population exam-ined and the timing of the research Several factors have been found to be associated with postpartum depression including poor social support and infant-related stressors6 Evidence indi-cates that postnatal depression may be underreported and this is of concern since the mental and psychological health of the mother can affect her relationship with her infant and thus the infantrsquos cognitive and emotional development5 Depressed moth-ers appear to look touch and talk to their infants less frequently and also appear to show fewer positive and more negative faces7 The vocalizations of mothers suffering with depression have also
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
been found to be less effective at promoting cognitive growth and learning in infants8
If researchers are interested in finding ways of providing sup-port for families of sick neonates then they must listen to what such families perceive their needs to be in order to avoid increas-ing anxiety and distress Furthermore the provision of appropri-ate support be it emotional informational or social will enhance parental coping abilities increase self-esteem and reduce anxiety It should be noted though that the research conducted around these issues has often taken lsquosupport needsrsquo as being synony-mous with lsquoinformation needsrsquo Such studies have examined the type the amount and quality of information that parents receive and perceive themselves as needing but have not explored in equal depth the perceived emotional support needs of families who have a sick infant In addition the needs of parents may change throughout their infantrsquos illness Ward examined the per-ceived needs of 52 parents of infants in an NICU9 Parents rated the needs of their hospitalized infant as most important along with the need to be reassured Interestingly they ranked their support needs as least important This research was conducted during the first week of the infantsrsquo hospitalization however which would explain the preoccupation of the parents with the infantrsquos health These results demonstrate that if researchers want to find ways of providing emotional support to parents of sick neonates they must be prepared not only to listen to parents but also to be flexible enough to satisfy the parentsrsquo changing needs and expectations
Interventions aimed at supporting parents
Most interventions that been evaluated in controlled studies have focused on supporting the motherndashinfant relationship and provid-ing information on infant development Many of these interven-tions have included the aim of improving the parental emotional state and thus psychological outcomes such as stress or anxi-ety have been assessed However few studies appear to include fathers This means that strategies implemented to provide emo-tional support to families of sick neonates are often derived from interventions tailored for mothers even though fathers may have different emotional needs
A wide range of interventions with mothers and infants has been evaluated in the NICU Increasing motherndashinfant contact through kangaroo care has been found to reduce maternal anxiety1011 and educational programmes delivered to fami-lies in the NICU have also been associated with reduced emo-tional difficulties in parents12ndash14 Kaaresen and colleagues implemented an intervention which consisted of eight sessions before discharge and four home visits all by trained nurses The sample included 71 premature infants in the intervention group 69 premature infants in the control group and 74 infants in the full-term control group The randomized controlled trial found that the intervention reduced parenting stress in both mothers and fathers of premature infants compared to controls to a level equivalent to parents in the term control group13 At 6 months corrected age mothers of preterm infants who had not received the intervention had total PSI scores which were 17 points higher than the mothers of infants born at term (an effect size of 057) A similar study evaluated the efficacy of an educationalndashbehavioural programmendashCreating Opportunities for
PaeDiaTrics anD cHilD HealTH 184 19
Parent Empowerment (COPE) ndash through a randomized controlled trial with 260 families of premature infants14 COPE was a four-phase educationalndashbehavioural programme which began as early as 2ndash4 d after mothers had given birth and continued until 1 week after discharge from the NICU The programme consisted of audiotaped and written infant behaviour information along with photographs which focused on common behaviours and characteristics of premature infants It also included various par-ent activities in the form of a four-phase workbook which aimed to assist mothers in the implementation of the experimental infor-mation COPE was found significantly to reduce maternal stress in the NICU as well as maternal anxiety and depressive symptoms after hospitalization In contrast a cluster randomized trial of a parenting intervention delivered to mothers of very premature infants from soon after birth showed no benefits for parenting stress1 The authors hypothesized that the intervention had not been of sufficient intensity particularly in the weeks surrounding discharge Neonatal care presents a significant barrier to parent-ing in the early weeks following a very preterm birth and so inter-ventions which focus on the developmental needs of infants and the parentndashchild relationship should particularly aim to support parents as they take on the parenting role There was also concern that the intervention had failed to reach those most at risk
Since large-scale projects can be costly to implement and may often fail to reach the families in most need it may be wiser to focus on intervention programmes which are more practical and easier to implement within a neonatal care setting Research has shown that even interventions which are based on one-off meet-ings with parents of sick neonates can be effective Jotzo and Poets examined the effect of an intervention programme aimed at reducing the severity of traumatic responses as a result of giv-ing birth prematurely15 Their programme consisted of a one-off intervention meeting along with additional psychological help throughout the hospitalization of the infant The meeting cov-ered a variety of issues including a reconstruction of the events shortly before and after the infantrsquos birth relaxation techniques discussion of coping strategies available resources and social support and support during emotional outbursts The measures used included the Impact of Event Scale (IES) and the Peritrau-matic Dissociative Experience Questionnaire At discharge the mothers who received the intervention were found to have a significantly lower traumatic impact as a result of premature birth Furthermore fewer mothers in the intervention group showed symptoms of clinically significant psychological trauma at discharge compared to mothers in the control group (36 vs 76)15 The lsquoParents Circle Programrsquo is another intervention with a similar structure16 This consisted of a 90 min session for parents with the aim of enhancing the developing relationship between parents and infants and to offer parents support A total of 104 parents (59 mothers and 45 fathers) and 44 members of hospital staff were asked to evaluate the programme and their results were analysed using content analysis Families reported gaining perspective on their situation feeling supported becom-ing aware of cues and optimizing interactions and becoming aware of available resources Parents and staff alike felt that participating in the intervention helped parents overcome the difficulties associated with the early time of their infantrsquos hos-pitalization Additional studies have also found positive results with fairly minimal interventions including discussion groups
7 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
in the NICU music during kangaroo care and pairing mothers of sick neonates with trained mothers who had been through similar experiences
Parent support programmes
Parent support programmes (PSPs) which are based in NICUs can provide parents with the opportunity to talk to parents who have been in similar situations and also to discuss their emo-tions with professionals who can help them cope with their situa-tion111718 The parent-to-parent support programme for mothers of preterm infants evaluated by Preyde and Ardal included edu-cational parental support group meetings and individual par-ent-to-parent support (primarily telephone support)19 Measures used included the Parental Stressor Scale NICU the State and the Trait Anxiety Inventories and the Beck Depression Inven-tory After 4 months of participation mothers in the intervention group reported lower levels of stress state anxiety and depres-sion compared to control group mothers The authors speculated however that the participants who were able to meet face to face with other parents were those who benefited the most Hurst conducted a comprehensive survey of an NICU-based PSP This PSP was provided in a variety of formats including a weekly parent support group hospital visitation and 24-h telephone sup-port20 Of the 477 participants 303 families used the PSP dur-ing a 2-year evaluation period with 78 using only one form of support and 18 using two forms Of a sub-sample of 48 parents asked to complete an evaluation of the PSP 92 stated that they would recommend such a programme to other parents Furthermore the majority of parents felt that it made them feel supported and helped them deal with their emotions20 This is an indication that such programmes can be very successful in sup-porting parents throughout their infantrsquos hospitalization It also shows that it can be beneficial to give parents several options and formats when it comes to such support services It is impor-tant to consider though that both the Hurst and the Preyde and Ardal studies found that some participants did not find the sup-port programmes helpful even reporting that they had caused them increased stress and anxiety Therefore it should not be assumed that support programmes will suit every individual and will provide the required support for all parents1920 NICUs need to be flexible enough to provide parents with a range of forms of support to choose from
The increased understanding of the strains that parents of sick neonates have to deal with has also led to efforts to improve customary practices in NICUs Family-centred care focuses on infants and their needs and attempts to redefine the relationship between parents and caregivers These practices strive to provide parents with support during their infantrsquos illness by focusing on freely sharing information and on the collaboration between parents and hospital staff Family-centred care has been found to be associated with several beneficial outcomes including improved parental satisfaction increased parental comfort staff satisfaction and decreased parental stress18 Research is already examining these practices and questioning how these can be improved further Such research reflects the increasing effort focused on lsquohumanizingrsquo the environment in NICUs in order to make parents feel more comfortable about spending time with their infants
PaeDiaTrics anD cHilD HealTH 184 19
Conclusion
Surprisingly few interventions have prioritized the provision of emotional support for parents of sick neonates or accounted for the changing needs and wishes of parents over the course of their infantrsquos care Large-scale supportive education-based inter-ventions have been shown to be effective in reducing parental distress However the feasibility and sustainability of such pro-grammes should also be considered Programmes which require significant additional resources can be expensive and there are also issues of training and quality control Interventions which require significant input from parents may also place additional burdens on families making them potentially less accessible to those most at risk Arguably the aim should be to explore ways of providing acceptable and effective informational support which could be complemented by emotional support from health professionals and from other parents in the unit Increasingly studies are exploring the use of computers and multimedia as an engaging flexible and cost-effective method of targeting indi-vidual needs and providing support and information Such com-puter-based and interactive multimedia interventions have been found to be successful with a range of patient groups and could therefore be examined as a complementary method of providing informational support to families with sick neonates
REfEREnCEs
1 Glazebrook c Marlow n israel c et al randomised trial of a
parenting intervention during neonatal intensive care Arch Dis Child
Fetal Neonatal Ed 2007 92 F438ndash443
2 singer lT salvator a Guo s collin M lilien l Baley J Maternal
psychological distress and parenting stress after the birth of a very
low-birth-weight infant JAMA 1999 281 799ndash805
3 shaw rJ Deblois T ikuta l Ginzburg K Fleisher B Koopman c
acute stress disorder among parents of infants in the neonatal
intensive care nursery Psychosomatics 2006 47 206ndash212
4 Hopper a sources of stress for parents of a sick neonate a
literature review Pediatr Nurs 2000 30 29ndash32
5 Davis l edwards H Mohay H wollin J The impact of very
premature birth on the psychological health of mothers Early Hum
Dev 2003 73 61ndash70
6 Bernazzani O saucier J-F David H Borgeat F Psychosocial
predictors of depressive symptomatology level in postpartum
women J Affect Disord 1997 46 39ndash49
7 Field T infants of depressed mothers Infant Behav Dev 1995 18
1ndash13
8 Kaplan Ps Bachorowski J-a Zarlengo-strouse P child-directed
speech produced by mothers with symptoms of depression fails
to promote associative learning in 4-month-old infants Child Dev
1999 70 560ndash570
9 ward K Perceived needs of parents of critically ill infants in
a neonatal intensive care unit (nicU) Pediatr Nurs 2001 27
281ndash286
10 lai Hl chen cJ Peng Tc et al randomized controlled trial of music
during kangaroo care on maternal state anxiety and preterm infantsrsquo
responses Int J Nurs Stud 2006 43 139ndash146
8 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
11 Tallandini Ma scalembra c Kangaroo mother care and mother-
premature infant dyadic interaction Infant Ment Health J 2006 27
251ndash275
12 Ohgi s Fukuda M akiyama T Gima H effect of an early intervention
programme on low birthweight infants with cerebral injuries
J Paediatr Child Health 2004 40 689ndash695
13 Kaaresen Pi ronning Ja Ulvund se Dahl lB a randomized
controlled trial of the effectiveness of an early-intervention program
in reducing parenting stress after preterm birth Pediatrics 2006
118 e9ndash19
14 Melnyk BM Feinstein nF alpert-Gillis l et al reducing premature
infantsrsquo length of stay and improving parentsrsquo mental health
outcomes with the creating opportunities for parent empowerment
(cOPe) neonatal intensive care unit program a randomized
controlled trial Pediatrics 2006 118 e1414ndash1427
15 Jotzo M Poets cF Helping parents cope with the trauma of
premature birth an evaluation of a trauma-preventive psychological
intervention Pediatrics 2005 115 915ndash919
16 Pearson J andersen K evaluation of a program to promote positive
parenting in the neonatal intensive care unit Neonatal Netw 2001
20 43ndash48
17 roman l lindsay J Boger r et al Parent-to-parent support
initiated in the neonatal intensive care unit Res Nurs Health 1995
18 385ndash394
18 Meyer ec coll cTG lester BM Boukydis cFZ McDonough sM Oh w
Family-based intervention improves maternal psychological well-
being and feeding interaction of preterm infants Pediatrics 1994
93 241ndash246
PaeDiaTrics anD cHilD HealTH 184 19
19 Preyde M ardal F effectiveness of a parent ldquobuddyrdquo program for
mothers of very preterm infants in a neonatal intensive care unit
CMAJ 2003 168 969ndash973
20 Hurst i One size does not fit all Parentsrsquo evaluations of a support
program in a newborn intensive care nursery J Perinat Neonatal
Nurs 2006 20 252ndash261
Practice points
bull Parents of sick neonates experience significant distress and
exhibit higher levels of stress anxiety and depression than
parents of healthy infants
bull educational support emotional support and increased
motherndashinfant contact have been shown to promote maternal
well-being
bull emotional support for fathers has been largely neglected in
the research literature
bull Parents benefit from a choice of supportive facilities which
could include face-to-face sessions with health professionals
telephone support hospital visitation parent-to-parent
support and unit-based group support meetings
bull Parentsrsquo support needs can change during their infantrsquos
hospitalization and not all parents want or benefit from the
provision of additional information and emotional support in
the neonatal unit
9 copy 2008 elsevier ltd all rights reserved
Personal Practice
When should enteral feeds be started in preterm infantsnicholas D embleton
AbstractPaediatricians are regularly faced with the question of when best to start
enteral feeds in preterm infants this is important as longer term out-
come may be compromised by sub-optimal nutrition in early life clinical
factors that may affect the decision to start and the risk and benefits
are discussed
Keywords breast milk feeding nutrition parenteral nutrition
Key points in the history
Alice is lsquonutritionally vulnerablersquo and whilst this may not be immediately apparent it will affect her long term outcome Her energy stores are extremely limited and consist primarily of pro-tein She has less than 5 fat and little energy associated with stored glycogen She is losing about 1 gkgd protein equivalent so she needs at least that and a minimum of 50ndash60 kcalkg of energy just to maintain the status quo let alone grow
Her weight is on the 25th centile Review of any antenatal his-tory may reveal whether fetal growth was normal Fetal growth retardation can occur with a weight greater than 10th centile The presence of antenatal absent or reversed end diastolic flow in the umbilical artery indicates poor gut blood flow This increases the risk of necrotizing enterocolitis (NEC) and might suggest a more cautious approach to starting feeds1
She has no important cardiovascular problems but if she were hypotensive gut blood flow may be low There is no umbilical
Nicholas D Embleton BSC (Hons) MBBS (Hons) MD FRCPCH is Consultant in
Neonatal Medicine at Newcastle Neonatal Service Royal Victoria
Infirmary Newcastle upon Tyne NE1 4LP UK
Should you start feeds at a day of age
alice was born following spontaneous labour at 30 weeksrsquo
gestation she weighed 1300 g and is now 18 h old she was
briefly ventilated and then extubated to continuous positive
airway pressure 12 h ago in 35 oxygen she has had caffeine
citrate but still has intermittent episodes of self-correcting
apnoea she was commenced on iv 10 dextrose but this was
replaced by a parenteral amino acid solution (referred to as
lsquotPnrsquo) along with intralipid at 0900 this morning serum glucose
is 11 mmoll and blood pressure is 42 systolic
PaeDiatrics anD cHilD HealtH 184 20
arterial catheter in situ but there is no good evidence that this should delay the decision to start feeds Her glucose is high but this is quite common in a baby like this Could this be a sign of sepsis Caffeine does not affect the incidence of NEC2 The great-est risk factor for NEC in this case is prematurity
What else might be found on examination
Up until 24 h ago she was swallowing large amounts of amniotic fluid What will have changed since then
General examination should confirm peripheral perfusion lsquogestaltrsquo view (does she look lsquowellrsquo) and cardiovascular status lsquoBowel soundsrsquo are not usually helpful
The most important variable likely to affect gut perfusion is the arterial duct Precordial lsquoheaversquo and a loud murmur are sug-gestive but it is possible to have a significant ductal shunt in a baby with a normal examination Cardiac ultrasound will con-firm this diagnosis It might be better to treat a large shunt first with indometacin and to delay starting feeds for a further 24 h
It is not possible to assess gut perfusion clinically but normal perfusion elsewhere (adequate urine output usually indicates adequate renal perfusion) would be reassuring Most preterm babies have a few abdominal lsquoloopsrsquo visible but a distended abdomen with many palpable loops suggests ileus This might be secondary to sepsis or poor gut blood flow Preterm babies do not pass much meconium in the first 24ndash48 h
Balance of risks between starting and withholding feeds
Alice requires 35ndash4 gkgd of protein and 120 kcalkgd to grow3 This will initially be provided parenterally Delaying feeds increases the risk of gut villous atrophy and prolongs the need for lsquototal parenteral nutrition (TPN)rsquo TPN requires intravenous access and so increases the risk of sepsis and when prolonged use is required combined with the lack of enteral feeding may result in hepatic impairment
Delaying feeds may allow a gut that has been chronically under-perfused to re-establish more normal perfusion although normal gut endocrine function digestive enzyme upregulation and motility require a source of intraluminal nutrients1 A recent study suggested benefit from delaying the introduction of feeds4 but methodologi-cal problems exist5 Although a Cochrane meta-analysis suggested no benefit only two studies were included6 A large UK-based trial is examining the effect of early or late feeding in preterm infants who were born growth retarded following identification of antena-tal absent or reversed end diastolic flow in the umbilical artery7
When starting feeds what volume should be used
There are no good data to guide this decision We start with 24 mlkg (1 mlkgh) and then increase by this amount each day Most babies achieve full enteral feeds (ge150 mlkgd) by a week of age Feeding guidelines improve the outcome8 Measure-ment or assessment of gastric aspirates is not consistently useful in predicting subsequent feeding intolerance or development of NEC Aspirate volumes equivalent to or sometimes greater than the amount given in the preceding 1ndash2 h are usually normal Most aspirates have a greenish colour Thick bloody or intensely bile-stained aspirates require detailed assessment
0 copy 2008 elsevier ltd all rights reserved
Personal Practice
What else affects decisions and outcome
Feeding success is affected by sepsis and NEC Scrupulous atten-tion should be paid to hand washing and intravenous access and blood sampling should be minimized There is no good evidence to support the routine use of pro-kinetic agents or H2 blockers
The most important clinical intervention affecting the occur-rence of NEC is the use of breast milk9 All efforts should be directed at persuading parents of the benefits and supporting the process Some clinicians delay starting feeds for a further 24 h whilst expressed breast milk becomes available Donor breast milk might be equally efficacious10
RefeRenceS
1 Dorling J Kempley s leaf a Feeding growth restricted preterm
infants with abnormal antenatal Doppler results Arch Dis Child Fetal
Neonatal Ed 2005 90 F359ndash363
2 schmidt B roberts rs Davis P et al caffeine therapy for apnea of
prematurity N Engl J Med 2006 354 2112ndash2121
PaeDiatrics anD cHilD HealtH 184 20
3 embleton nD Pang n cooke rJ Postnatal malnutrition and growth
retardation an inevitable consequence of current recommendations
in preterm infants Pediatrics 2001 107 270ndash273
4 Berseth cl Bisquera Ja Paje VU Prolonging small feeding volumes
early in life decreases the incidence of necrotizing enterocolitis in
very low birth weight infants Pediatrics 2003 111 529ndash534
5 Menon G Boyle eM embleton nD et al introduction of enteral
feeds in preterm infants Pediatrics 2004 114 327ndash328
6 Kennedy Ka tyson Je chamnanvanikij s early versus delayed
initiation of progressive enteral feedings for parenterally fed low
birth weight or preterm infants Cochrane Database Syst Rev 2000
cD001970
7 wwwnpeuoxacukadept
8 Patole sK de Klerk n impact of standardised feeding regimens on
incidence of neonatal necrotising enterocolitis a systematic review
and meta-analysis of observational studies Arch Dis Child Fetal
Neonatal Ed 2005 90 F147ndash151
9 lucas a cole tJ Breast milk and neonatal necrotising enterocolitis
Lancet 1990 336 1519ndash1523
10 Boyd ca Quigley Ma Brocklehurst P Donor breast milk versus
infant formula for preterm infants systematic review and meta-
analysis Arch Dis Child Fetal Neonatal Ed 2007 92 F169ndash175
1 copy 2008 elsevier ltd all rights reserved
self-assessment
Case 1A term male infant born to consanguineous parents is assessed at 24 h of age due to poor feeding profuse yellow watery diar-rhoea and irritability He weighed 32 kg at birth and delivery was uneventful There was no polyhydramnios He has been breastfed since birth On examination he is pale with a non-tender but distended abdomen and reduced bowel sounds His weight is 275 kg and he looks dehydrated Examination is otherwise normal
Initial investigations (normal values in parentheses) showed
sodium 149 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 65 mmollitre (25ndash75)
creatinine 147 μmollitre (40ndash110)
chloride 119 mmollitre (95ndash105)
haemoglobin 172 gdl (140ndash200)
White blood cell count 80 times 109litre (100ndash260)
Platelet count 302 times 109litre (150ndash400)
arterial blood gas
ph 720 (730ndash745)
PcO2 23 kPa (46ndash60)
Bicarbonate 68 mmollitre (220ndash260)
Base excess minus186 mmollitre (minus20 to +20)
lactate 59 mmollitre (06ndash24)
An abdominal X-ray shows distended bowel loops with no intramural thickening or pneumoperitoneum (Figure 1)
He was given nil by mouth and received intravenous fluids and antibiotics His dehydration improved but the metabolic acidosis and diarrhoea persisted despite receiving no enteral feeds and the commencement of total parenteral nutrition Blood and stool cultures were negative
1 Which of the following best describes these results Choose ONE answer ONLY from the followingA Hypernatraemia hyperchloraemic metabolic acidosis
with increased anion gapB Hypernatraemia hyperchloraemic metabolic acidosis
with normal anion gap
Manish Sadarangani BM BCh MA MRCPCH is Clinical Research Fellow
at the Department of Paediatrics University of Oxford Centre for
Clinical Vaccinology and Tropical Medicine Churchill Hospital
Oxford OX3 7LJ UK
Shabna Rajapaksa MB BChir MA MRCPCH is Specialist Registrar in
Paediatrics at the Paediatric Intensive Care Unit John Radcliffe
Hospital Oxford OX3 9DU UK
Nicholas Mann MD FRCP FRCPCH DCH is Consultant Paediatrician at the
Department of Paediatrics Royal Berkshire Hospital Reading RG1
5AN UK
self-assessment
C Hypernatraemic dehydration and compensated metabolic acidosis
D Acute renal failureE Renal tubular acidosis
2 What is the likely diagnosis Choose ONE answer ONLY from the followingA Hirschsprung disease ndash long segmentB Cystic fibrosis with meconium ileusC Microvillus inclusion diseaseD Cowrsquos milk protein intoleranceE Lactose intolerance
3 What is the investigation of choice Choose ONE answer ONLY from the followingA Rectal biopsy with staining for acetylcholine receptorsB Immunoreactive trypsinC Gastrointestinal endoscopy and biopsyD Stool microscopy and cultureE Stool reducing substances
Case 2A 4-year-old boy presents with a 3 d history of jaundice and a florid rash He has had orange urine and there is no change in his stool colour His family originate from Kosovo and have lived in the UK for the last 8 years He has never left the UK There is no history of blood transfusion or sex-ual abuse The grandmother was recently diagnosed with hepatitis B
On examination he is well apyrexial and mildly jaundiced with cervical and axillary lymphadenopathy He has an exten-sive papular rash over the face extremities and trunk (Figure 2) There is 3 cm hepatomegaly with no splenomegaly or ascites Examination is otherwise normal
Figure 1 abdominal X-ray of baby
Paediatrics and child health 184 202 copy 2008 elsevier ltd all rights reserved
self-assessment
Initial investigations are as follows
haemoglobin 110 gdl (113ndash135)
White blood cell count 108 times 109litre (50ndash150)
Platelet count 278 times 109litre (150ndash400)
inr 10 (08ndash12)
aPt ratio 10 (08ndash13)
sodium 140 mmollitre (135ndash145)
Potassium 42 mmollitre (35ndash50)
Urea 56 mmollitre (25ndash75)
creatinine 65 μmollitre (45ndash120)
total bilirubin 66 μmollitre (0ndash15)
conjugated bilirubin 23 μmollitre (0ndash10)
alanine aminotransferase (alt) 2033 iUlitre (0ndash35)
alkaline phosphatase 987 iUlitre (71ndash234)
Gamma-glutamyl transferase (GGt) 870 iUlitre (0ndash51)
1 What is the name of this rash Choose ONE answer ONLY from the followingA Erythema multiformeB Erythema migransC GianottiminusCrosti syndromeD EczemaE Dermatitis herpetiformis
2 What is the most likely diagnosis Choose ONE Answer ONLY from the followingA Autoimmune hepatitisB Hepatitis BC Hepatitis DD Wilson diseaseE Alpha-1 antitrypsin deficiency
3 What is the best means of management Choose ONE answer ONLY from the followingA Isolation until the jaundice disappearsB ImmunosuppressionC Copper chelating agents and genetic counsellingD Patient and family education with consideration of
antiviral agentsE Liver transplantation
Case 3A 10-month-old boy presents with 3 weeks of vomiting and constipation ndash he is passing hard stools every 2ndash3 days He has fallen from the 9th to below the 04th centile in the last 6 weeks He passed meconium within the first 24 h of life On examina-tion he looks pale and there are some dysmorphic features ndash a short nose long philtrum and wide mouth He has normal heart sounds with a grade 3 ejection systolic murmur loudest at the upper right sternal edge Examination is otherwise normal
Initial investigations are as follows
haemoglobin 91 gdl (113ndash141)
total white blood cell count 124 times 109litre (60ndash170)
Platelet count 407 times 109litre (150ndash400)
sodium 144 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 78 mmollitre (25ndash75)
creatinine 78 μmollitre (45ndash120)
albumin 52 glitre (35ndash50)
corrected calcium 384 mmollitre (238ndash263)
Phosphate 167 mmollitre (099ndash157)
1 What is the most likely diagnosis Choose ONE answer ONLY from the followingA HyperparathyroidismB Acute leukaemiaC Williams syndromeD Hypervitaminosis DE Familial hypocalciuric hypercalcaemia
2 Which investigation would be most useful in establishing the diagnosis Choose ONE answer ONLY from the followingA Intact parathyroid hormone assayB Blood filmC Fluorescent in-situ hybridization for 7q1123 deletionD 25-hydroxyvitamin D assayE Urine calciumcreatinine ratio
3 Which of the following treatments would not be suitable for this patient Choose ONE answer ONLY from the followingA Low calcium dietB Normal saline infusionC FurosemideD CorticosteroidsE Bisphosphonates
Case 4A 10-week-old girl presents with a 2-day history of poor feed-ing Her mother has been concerned about weakness since birth She only has a flicker of movement in the arms none in the legs and has a weak cry She has been passing urine and opening her bowels normally She was born at full term by normal delivery and did not require any resuscitation at birth Normal fetal movements were felt antenatally and there was no polyhydramnios She is the first child of non- consanguineous parents and there is no significant family his-tory On examination she is alert and fixing and following appropriately She has a weak cry and a weak suck There is reduced central and peripheral tone with marked head lag
Figure 2 rash found on examination
Paediatrics and child health 184 203 copy 2008 elsevier ltd all rights reserved
self-assessment
Muscle power is grade 3 out of 5 in the arms and legs There is no muscle or tongue fasciculation and she has absent reflexes throughout The remainder of the examination is normal
Electromyogram shows irregular polyphasic motor unit potentials with marked instability consistent with a dener-vating and re-innervating process (Figure 3)
1 Which of the following additional investigations may be helpful Choose ONE answer ONLY from the followingA Nerve conduction studiesB Creatine kinase assayC Muscle biopsyD SMN1 gene analysisE All of the above
2 What is the most likely cause of this childrsquos symptoms Choose ONE answer ONLY from the followingA Congenital myotonic dystrophyB Duchenne muscular dystrophyC PraderminusWilli syndromeD Spinal muscular atrophyE Mitochondrial myopathy
3 What is the mode of inheritance of this disease Choose ONE answer ONLY from the followingA X-linked recessiveB Autosomal recessiveC Autosomal dominantD MitochondrialE Sporadic
Case 5A 13-year-old girl presents with a 3-week history of fever up to 40degC night sweats and headache She has a reduced appetite with some weight loss She has no other specific symptoms She was on holiday in China 7 months ago On examination she looks well and has a temperature of 387degC There is no lymphadenopathy and no rashes Examination is entirely normal
Results of investigations are as follows
haemoglobin 126 gdl (120ndash160)
total white blood cell count 132 times 109litre (43ndash108)
neutrophil count 115 times 109litre (25ndash75)
Platelet count 244 times 109litre (150ndash400)
Blood film neutrophilia with left shift
erythrocyte sedimentation rate 63 mmh (1ndash20)
c-reactive protein 219 mglitre (0ndash5)
Blood culture Streptococcus intermedius
from anaerobic bottle only
csf culture negative
Magnetic resonance imaging (MRI) of the brain shows acute frontal sinusitis with a large intracranial frontal extra-dural empyema (Figure 4)
1 Which of the following would be appropriate management Choose ONE answer ONLY from the followingA A 12-week course of intravenous antibioticsB Drainage of the frontal sinus followed by 2 weeks of
intravenous antibioticsC Drainage of the empyema followed by 2 weeks of
intravenous antibioticsD Drainage of the empyema and the frontal sinus
followed by 2 weeks of oral antibiotics
1151
1152
1153
1154
1155
1156
1157
1158
1159
1200
50ms 1mV
Figure 3 electromyogram recording from the patient Figure 4 Parasagittal section from mri scan of patient
Paediatrics and child health 184 204 copy 2008 elsevier ltd all rights reserved
self-assessment
E Drainage of the empyema and the frontal sinus followed by 8 weeks of intravenous antibiotics
2 Streptococcus intermedius is a potential pathogen in which of the following infections Choose ONE answer ONLY from the followingA Liver abscessB Urinary tract infectionC MeningitisD Thoracic empyemaE Pneumonia
3 Which of the following statements regarding lsquopyrexia of unknown originrsquo in children is false Choose ONE answer ONLY from the followingA Malignancy is the underlying pathology in 5ndash15 of
casesB An aetiology will be found in over 90 of casesC The most common cause is infectionD A rheumatological cause is found in 10ndash20 of casesE Familial Mediterranean fever can occur in children of
non-Mediterranean ethnicity
Answers
Case 11 AThe anion gap is a useful tool to differentiate the causes of a metabolic acidosis It is calculated by the equation
Anion gap = [Na K ] [Cl HCO ]3+ + minus minus+ minus +
It represents the effect of unmeasured anions on the plasma pH and is normally 10ndash18 mmollitre
2 CMicrovillus inclusion disease is a severe autosomal recessive enteropathy that is typically apparent within hours or days after birth It is the second most common cause of protracted diarrhoea in the newborn after infectious causes It is characterized by severe yellow watery diarrhoea and malabsorption due to hypoplasia andor atrophy of the villi of the small intestine secondary to an inherited defect in the brush border membrane This results in severe dehydration malnutrition and metabolic acidosis due to bicarbonate loss from the gut
3 CDiagnosis of microvillus inclusion disease is made on small bowel biopsy Electron microscopy findings are of intracellular brush border inclusions and densely packed apical cytoplasmic vesicular bodies indicating microvillous atrophy There is no cure Treatment is supportive with total parenteral nutrition and consideration of small bowel transplantation
Further reAding
Goulet O ruemmele f causes and management of intestinal failure
in children Gastroenterology 2006 130(suppl 1) s16ndash28
rhoads Jm Vogler rc lacey sr et al microvillus inclusion disease
In vitro jejunal electrolyte transport Gastroenterology 1991
100 811ndash817
Case 21 CGianottindashCrosti syndrome is a distinct self-limiting rash commonly associated with viral infections in children between 2 and 6 years of age It presents as multiple pink to redminusbrown papules or papulovesicles which may be pruritic and can become confluent Gianotti and Crosti initially described the exanthema as associated with hepatitis B virus and they termed it papular acrodermatitis of childhood It can occur in several viral diseases eg hepatitis A B and C coxsackie viruses and cytomegalovirus
2 BHepatitis is a syndrome characterized by inflammation or injury of liver cells which may develop into cell necrosis and subsequently fibrosis andor cirrhosis Biochemically there are raised liver enzymes The degree of transaminase elevation does not correlate with the severity of the disease process Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of viral hepatitis
3 DHepatitis B infection is transmitted via blood sexually or vertically Infection may be acute or chronic Diagnostic markers are the presence of surface antigen (HBsAg) and HBV DNA The presence of e antigen (HBeAg) indicates high infectivity Infected newborns have a 95 risk of becoming carriers this risk decreases with infection acquired later in childhood Approximately 15ndash25 of HBV carriers will die from cirrhosis or hepatocellular carcinoma Extrahepatic findings are more common in older children and include membranous glomerulonephritis and GianottiminusCrosti syndrome Fulminant hepatic failure occurs in severe cases resulting in persistent jaundice encephalopathy and coagulopathy Management includes counselling family members monitoring for ongoing liver disease and consideration of antiviral therapy
Further reAding
Brandt O abeck d Gianotti r Burgdorf W Gianotti crosti
syndrome J Am Acad Dermatol 2006 54 136ndash145
slowik mK Jhaveri r hepatitis B and c viruses in infants and
young children Semin Pediatr Infect Dis 2005 16 296ndash305
Case 31 CHypercalcaemia is uncommon in infancy The most common symptoms in this age group are irritability vomiting and constipation It may be a manifestation of Williams syndrome vitamin D or calcium excess as well as disorders associated with reduced bone formation such as hypophosphatasia or increased bone resorption such as malignancy Occasionally
Paediatrics and child health 184 205 copy 2008 elsevier ltd all rights reserved
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-
SympoSium neonatology
A systematic approach to blood gas analysis
1 Collect the relevant information
bull type of gas ndash capillary or arterial
bull Current respiratory support ndash document level
bull transcutaneous Co2 and Sao2 levels
bull Clarify no significant clinical events before sampling
2 pH accept a range between 730 and 745 in newborn
babies this is lower than in older children is there an
alkalosis (pH gt 745) or an acidosis (lt 730)
3 Co2 aim for a range between 45 and 65 kpa a paCo2 level
more than 65 kpa suggests inadequate alveolar ventilation
while less than 45 kpa suggests hyperventilation Correlate
values with non-invasive measures
4 o2 Can only be assessed from arterial gases aim for pao2
between 60 and 80 kpa Correlate results with pulse
oximetry levels
5 HCo3 and base excess normal HCo3 level is between 20 and
24 mmollitre and bases excess +3 to minus3
6 anion gap look at the anion gap and lactate to help identify
the cause of an acidosis normal lactate levels should be less
than 2 mmollitre
7 Respiratory or metabolic compensation look at the pH and
assess whether it is appropriate for the Co2 level or is there
evidence of compensation
8 interpret use both the clinical history and blood gas
findings to help you identify the primary problem aim your
management at treating the underlying cause
9 Reassess if clinical management changes have been made
repeat the blood gas after an appropriate time interval to
ensure improvement
Table 2
provides a highly accurate and reliable method for measuring PaCO2 through the skin it can however be technically difficult may cause tissue damage and is of limited reliability when peripheral perfusion is reduced25 Continuous end-tidal CO2 measurements correlate well with arterial CO2 values in patients with normal ventilation and perfusion however in babies with lung disease alveolar collapse small tidal volumes and rapid respiratory rates can make these measurements unreliable26 Despite its limitations transcutaneous monitoring provides the best method for CO2 trend monitoring in the neonatal intensive care unit (NICU)25
Oxygen saturation levels can be continuously measured non-invasively using pulse oximetry While oximetry is easy to perform and accurate on occasion SaO2 levels obtained may be unreliable when tissue perfusion is poor or with movement artefact SaO2 monitoring is highly sensitive at detecting hypoxia but is limited in detecting hyperoxia as at levels more than 90 small changes in SaO2 may result in unacceptably large increases in PaO227 It is therefore essential that SaO2 alarm limits are set for all neonates receiving respiratory support to detect hypoxia and prevent hyperoxia1627
Continuous non-invasive monitoring provides invaluable information when managing complex infants in the NICU but it does not replace the need for regular blood gas analysis
paeDiatRiCS anD CHilD HealtH 184 17
ReFeRenCeS
1 Kellum Ja Determinants of blood pH in health and disease
Crit Care 2000 4 6ndash14
2 Quigley R Baum m neonatal acid base balance and disturbances
Semin Perinatol 2004 28 97ndash102
3 Brouillette Rt Waxman DH evaluation of the newbornrsquos blood gas
status Clin Chem 1997 43 215ndash221
4 Chan JC acid-base disorders and the kidney Adv Pediatr 1983 30
401ndash471
5 Siggaard-andersen o the pH-log pCo2 blood acidndashbase nomogram
revised Scand J Lab Invest 1962 14 598ndash604
6 Saetta m mortola Jp interaction of hypoxic and hypercapnic stimuli
on breathing pattern in the newborn rat J Appl Physiol 1987 62
506ndash512
7 Baum m Quigley R postnatal renal development in Seldin DW
giebisch g eds the kidney physiology and pathophysiology new
york lippincott Williams and Wilkins 2000 p 703ndash726
8 ortiz la Quan a Weinberg a et al effect of prenatal
dexamethasone on rat renal development Kidney Int 2001 59
1663ndash1669
9 gabow pa Kaehny WD Fennessey pV goodman Si gross pa
Schrier RW Diagnostic importance of an increased serum anion gap
N Engl J Med 1980 303 854ndash858
10 lorenz Jm Kleinman li markarian K oliver m Fernandez J Serum
anion gap in the differential diagnosis of metabolic acidosis in
critically ill newborns J Pediatr 1999 135 751ndash755
11 Deshpande Sa platt mp association between blood lactate and
acid-base status and mortality in ventilated babies Arch Dis Child
1997 76 F15ndash20
12 Stewart pa modern quantitative acid-base chemistry Can J Physiol
Pharmacol 1983 61 1444ndash1461
13 Dakshinamurti S pathophysiologic mechanisms of persistent
pulmonary hypertension of the newborn Pediatr Pulmonol 2005
39 492ndash503
14 mourani pm ivy DD gao D abman SH pulmonary vascular
effects of inhaled nitric oxide and oxygen tension in
bronchopulmonary dysplasia Am J Respir Crit Care Med 2004
170 1006ndash1013
15 Deulofeut R Critz a adams-Chapman i Sola a avoiding hyperoxia
in infants le 1250 g is associated with improved short- and long-
term outcomes J Perinatol 2006 26 700ndash705
16 Chow lC Wright KW Sola a Can changes in clinical practice
decrease the incidence of severe retinopathy of prematurity in very
low birth weight infants Pediatrics 2003 111 339ndash345
17 Boylan gB young K panerai RB Rennie Jm evans DH Dynamic
cerebral autoregulation in sick newborn infants Pediatr Res 2000
48 12ndash17
18 Kaiser JR gauss CH pont mm Williams DK Hypercapnia during
the first 3 days of life is associated with severe intraventricular
hemorrhage in very low birth weight infants J Perinatol 2006 26
279ndash285
19 Fabres J Carlo Wa phillips V Howard g ambalavanan n Both
extremes of arterial carbon dioxide pressure and the magnitude of
fluctuations in arterial carbon dioxide pressure are associated with
severe intraventricular hemorrhage in preterm infants Pediatrics
2007 119 299ndash305
20 thome uH Carroll W Wu tJ et al outcome of extremely preterm
infants randomized at birth to different paCo2 targets during the
first seven days of life Biol Neonate 2006 90 218ndash225
6 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
21 Carlo Wa Stark aR Wright ll et al minimal ventilation to prevent
bronchopulmonary dysplasia in extremely-low-birth-weight infants
J Pediatr 2002 141 370ndash374
22 okumura a Hayakawa F Kato t et al Hypocarbia in preterm
infants with periventricular leukomalacia the relation between
hypocarbia and mechanical ventilation Pediatrics 2001 107
469ndash475
23 peters o Ryan S matthew l Cheng K lunn J Randomised
controlled trial of acetate in preterm neonates receiving parenteral
nutrition Arch Dis Child 1997 77 F12ndash15
24 yildizda D yapiciolu H yilmaz Hl Sertdemir y Correlation of
simultaneously obtained capillary venous and arterial blood gases
of patients in a paediatric intensive care unit Arch Dis Child 2004
89 176ndash180
25 aliwalas ll noble l nesbitt K et al agreement of carbon
dioxide levels measured by arterial transcutaneous and end tidal
methods in preterm infants 28 weeks gestation J Perinatol 2005
25 26ndash29
26 Hagerty JJ Kleinman me Zurakowski D et al accuracy of a new
low-flow sidestream capnography technology in newborns a pilot
study J Perinatol 2002 22 219ndash225
paeDiatRiCS anD CHilD HealtH 184 17
27 poets CF Wilken m Seidenberg J Southall Dp von der Hardt H
Reliability of a pulse oximeter in the detection of hyperoxemia
J Pediatr 1993 122 87ndash90
Practice points
bull a stable extracellular pH is important for optimal cellular
functioning
bull abnormalities in acidndashbase balance are regulated by buffer
systems and the respiratory and renal tract
bull maintaining a stable pH is challenging for newborn babies
due to their high rates of acid production and immature
regulatory mechanisms
bull arterial or capillary blood gases provide an effective way to
monitor acidndashbase balance in newborns
bull Blood gases should be analysed in a structured manner
assessing pH and then respiratory and metabolic components
bull the treatment of acidndashbase abnormalities should be directed
at the underlying problem not merely at correcting pH
7 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Recognition and management of neonatal seizuresmalcolm levene
AbstractSeizures are the most common major manifestation of central nervous
system dysfunction in the newborn there are many causes but perina-
tal asphyxia and haemorrhagicinfarction lesions account for about 75
there is now considerable evidence that frequent but short seizures in
the neonate affect subsequent neurodevelopmental outcome Studies
using eeg or modified continuous tracing of eeg activity (aeeg or CFm)
have shown that there is often electroconvulsive dissociation this re-
fers to poor correlation between electrical seizures and clinical seizures
Commonly used anticonvulsants appear to increase electroconvulsive
dissociation effective management of neonatal seizures has proved very
disappointing and less than 50 of seizures are abolished by first-line
anticonvulsant medication (phenobarbitone or phenytoin) Drugs such
as midazolam and lidocaine may further reduce seizures but require
more evaluation the challenge is to assess new and more effective anti-
convulsants which are themselves associated with little neurotoxicity
Keywords antiepileptic drugs eeg neonatal seizures neurodegeneration
Convulsions are the most common major neurological sign seen in newborn infants and their incidence estimated from large population studies is 26 per 1000 live births1 Premature infants are over four times more likely to have convulsions than full-term infants12 Neonatal status epilepticus (continuous seizure activity lasting 30 min or more) diagnosed clinically is rare and accounts for only 5 of infants with seizures1 although this is now recognized more frequently as the result of continuous EEG monitoring3
Neonatal convulsions are described as presenting in a num-ber of different ways and various seizure types can be seen in the same baby over a number of hours The frequencies of the various patterns of seizure activity are given in Table 1 In very premature babies and to a lesser extent in term infants minor movement abnormalities may be difficult to identify as subtle seizures These include lip smacking tongue thrusting mouth-ing pedalling type movements of the lower limbs or swimming movements of the arms Apnoea can be a common manifesta-tion of subtle seizures The signs can be protean and vary from baby to baby or even in the same baby Virtually any stereotypic
Malcolm Levene MD FMedSc FRCPCH FRCH is Professor and Head of
Department of Paediatrics and Child Health at University of Leeds Leeds
and Honorary Neonatologist at Leeds General Infirmary Leeds UK
paeDiatRiCS anD CHilD HealtH 184 178
movement may be a manifestation of a seizure disorder in the newborn
Aetiology
The more carefully the fitting baby is investigated the more likely it is that a cause for the seizures will be found A number of recent papers have described the aetiology of neonatal con-vulsions after extensive investigations14 Tekgul et al4 recently studied a consecutive group of full-term infants with evidence of neonatal convulsions (recognized both clinically and on EEG) and reported their outcome Table 2 summarizes these data as well as risk of moderate or severe disability for each causative factor Perinatal asphyxia is the commonest cause for convul-sions in term infants with haemorrhagic or ischaemic lesions also being common
Overall the prognosis for the group of term babies with con-vulsions was good 72 had a favourable outcome Where asphyxia (hypoxicndashischaemic insult) is the cause of neonatal convulsions the outcome is poor in 50 The prognosis for neonatal convulsions when they were due to arterial or cere-brovenous infarction or intracranial haemorrhage was generally good Individually inborn errors are a very rare cause of neo-natal convulsions but in view of the treatable nature of some of these it is essential that these be considered and investigated appropriately5
Patterns of seizure activity in the newborn
Movement pattern Frequency ()
Clonic 50
tonic 20
Subtle 10ndash35 depending on maturity
myoclonic 5
Table 1
Cause incidence and outcome of neonatal convulsions in term infants14
Aetiological factor Incidence () Poor outcome ()
asphyxia 38ndash40 50
Cerebral arteriovenous
infarction
20 0
intracranial haemorrhage 12ndash20 13
Congenital cerebral anomaly 5ndash10 100
Hypoglycaemiahypocalcaemia 3ndash19
infection 3ndash20
inborn error of metabolism 1
unknown cause 10ndash13 0
Refers to moderate and severe neurodevelopmental abnormalitynumbers too small to make meaningful predictions
Table 2
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Controversies in the clinical management of neonatal seizures
In recent years we have learnt much more about the neurobi-ology of seizures and their effect on the developing brain The neonatal brain is in a neurophysiologically hyperexcitable state compared to the more mature brain and therefore is more prone to seizure activity This is due largely to a relative excess of GABA neuroreceptors GABA receptors are usually inhibitory but in the immature brain they have a paradoxically excitatory effect This changes at about term in primates and with progressive develop-ment they adopt a neuroinhibitory role6
The propensity to seizures in the neonatal brain makes resolv-ing the balance of risks between continuing seizure activity on the one hand against potentially adverse effects of therapy on the other a very important equation Added to this is the problem of accurately diagnosing neonatal seizures and whether commonly used anticonvulsants are successful in controlling them
These conundrums can be posed as a series of challenging questions which are discussed below
Do neonatal convulsions cause brain injuryConvulsions are a sign of neurological compromise and may indi-cate significant underlying structural brain damage or biochemi-cal disturbance which may cause further brain damage in its own right There has been considerable debate about the scale of the disability that convulsions cause the immature brain over and above that due to the underlying cause Most of our knowledge comes from studies in rodents and these have provided some tentative answers to this question
Seizures in the mature brain lead to neuronal necrosis but studies in very young rat pups whose brain development is somewhat similar to full-term infants have shown that a series of five brief seizures on five successive days does not cause struc-tural neuronal damage but does produce morphological changes in hippocampal neurones and worryingly deficits in the rat learning and visual spatial memory function in adolescent and adult life7 A single prolonged neonatal convulsion in similarly immature rats does not produce any functional effects8 Others have shown that following priming of the neonatal rat brain by short seizures as described above a further insult comprising induction of status epilepticus in the same rats at an older age causes neuronal necrosis9 This has been referred to as the lsquotwo hit hypothesisrsquo10
A more specific question is does seizure activity in an already significantly compromised brain cause additional neuropathol-ogy Wirrell et al11 studied a series of immature rat pups with the induction of an hypoxicndashischaemic (asphyxial) insult fol-lowed by either chemically-induced fits or a control sham pro-cedure In the more severely asphyxiated animals the degree of brain damage was increased significantly in those that had the additional burden of induced seizures
In summary these studies show that the immature brain is more resistant to short frequent post-seizure damage than the mature brain but despite resulting in no loss of neuronal numbers the function of the brain is permanently affected in later life In the asphyxiated brain seizures appear to have an additional adverse effect on brain damage Furthermore the immature brain that has been lsquoprimedrsquo by early seizures is more
paeDiatRiCS anD CHilD HealtH 184 179
vulnerable to status epilepticus later in life It would appear from these data that frequent seizures in the human infant should be stopped and this begs the question as to whether currently used anticonvulsants effectively control neonatal seizures
Can we rely on clinical versus EEG diagnosis of neonatal convulsionsTraditionally the diagnosis of neonatal convulsions has been made by observation and description of the frequency of abnor-mal movements EEG has been technically difficult in the hostile electrical activity of a neonatal intensive care environment and considerable expertise is required for analysis of the trace It is usually not practical to undertake traditional EEG recordings at the time the baby shows abnormal movements More recently various technological developments have allowed more direct investigation of neuronal electrical activity by either video-EEG or compressed recording of the amplitude integrated EEG (aEEG or CFM)
Rennie et al3 at Kingrsquos College Hospital London have under-taken extensive evaluation of video-EEG and have found that this technique detects many convulsions not recognized by a single channel aEEG or CFM trace Of 19 infants with evidence of convulsions on EEG only four were recognized on CFM but this may have been due to the observersrsquo lack of experi-ence with this technique In other centres that have developed appropriate expertise aEEG or CFM has proved more sensitive to the detection of seizures Video-EEG studies have also shown that many movements interpreted by experienced clinicians to be seizures are not associated with abnormal cortical activity Conversely many electrical seizures are not associated with abnormal movements This is referred to as electroconvulsive dissociation
In summary clinical observation alone to detect the fitting baby is unreliable in that it may either over-detect seizure activ-ity which is not present on EEG or under-detect clinical seizures in infants with EEG-proven convulsions The decision as to which babies to treat with antiepileptic drugs therefore becomes somewhat arbitrary
Do anticonvulsants stop neonatal seizuresAlthough neonatal seizures are common there are few random-ized controlled trials assessing the benefits of antiepileptic drugs (AEDs) in the treatment of this condition Phenobarbitone is the most widely used first-line AED and in an Australasian study 95 of neonatologists and paediatric neurologists used this drug as first-line management12 The most commonly used loading dosage is 20 mgkg but regimens of up to 40 mgkg have been recommended (Table 3)13 Four trials have evaluated the effect of phenobarbitone in abolishing neonatal seizures Two of these studies used EEG to monitor response to the drug1415 and one compared phenobarbitone with phenytoin15 In the latter study seizures were completely controlled in only 43 of babies and in the group where phenytoin was the first drug used com-plete seizure control was achieved in 45 This study switched babies from their first AED to the other if complete control was not obtained on EEG monitoring after exposure to first-line therapy In babies who had been given phenobarbitone as first-line therapy seizure control was only achieved in 57 after phenytoin was added In those given phenytoin first complete
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Dosage regimens for first- second- and third-line anticonvulsants in the neonatal period
Loading dose Second loading dose if first
unsuccessfulMaintenance dose
phenobarbitone 20 mgkg by slow iv injection 10 mgkg iv 25ndash5 mgkg od
phenytoin 20 mgkg iv over 20 min not recommended
midazolam 150ndash200 μgkg iv infusion 1 μgkgmin iv infusion increasing to 5 μgkgmin
until favourable response
lidocaine 2 mgkg iv over 10 min 6 mgkgh for 6 h iv then 4 mgkgh for 12 h then
2 mgkgh for 12 h
lorazepam 005ndash01 mgkg by slow iv injection
Diazepam 03ndash04 mgkg iv over 3ndash5 min
lidocaine should not be used if the infant has previously been treated with phenytoin
Table 3
seizure control was achieved with the adding of phenobarbitone in 62
Boylan et al14 assessed the efficacy of phenobarbitone (20ndash40 mgkg iv over 20 min) in 14 babies monitored by video-EEG in only four was there complete abolition of seizures and in the other 10 electroconvulsive seizure activity increased whereas clinical evidence of seizures reduced This has been termed elec-troclinical dissociation and anticonvulsant drug use in the new-born appears to increase this feature They also showed that the babies least likely to respond to the first-line AED are those with the most abnormal background EEG
Two studies have evaluated the use of phenobarbitone in babies who had sustained significant asphyxial insult at birth Hall et al13 compared high-dose phenobarbitone (mean 39 mgkg) versus standard dose (27 mgkg) and reported fewer convul-sions and a significant reduction of severe disability or death in the high dose group (RR 030 CI 010ndash093) A recent study from India16 of babies with hypoxicndashischaemic encephalopathy ran-domized 25 babies to phenobarbitone (20 mgkg loading dose) and compared them with 20 control babies Only 2 of 25 (4) in the phenobarbitone group developed convulsions compared with 8 of 20 (40) in the control group (p = 001) Because of the specific enrolment criteria (asphyxial insult) neither of these studies is strictly comparable to the studies by Painter et al15 and Boylan et al14 whose intention was to assess the efficacy of first-line anticonvulsant therapy on convulsions of any cause diagnosed either clinically or by EEG
Other anticonvulsants used as second- and third-line drugs have been subject to few studies in the newborn Midazolam is administered as a bolus followed by continuous infusion A recent study17 has shown that in 10 of 13 neonates given intravenous midazolam for status epilepticus control of electri-cal seizures was achieved within the first hour of treatment having been previously shown to be refractory to phenobarbi-tone treatment Some of these babies required a second bolus infusion of midazolam to obtain control of all electrographic seizures
In some parts of Europe lidocaine is used as a third-line anti-convulsant Malingre et al18 evaluated 20 infants refractory to
paeDiatRiCS anD CHilD HealtH 184 180
both phenobarbitone and midazolam and who were then given lidocaine by continuous infusion Lidocaine was effective in abolishing electroconvulsive seizures diagnosed by aEEG in 76 of the treatment courses studied No babies developed cardiac arrhythmias a previously reported complication of lidocaine in older patients As a result of pharmacokinetic studies the dosage regimen has been modified (see Table 3)
In summary phenobarbitone is effective in seizure control in less than 50 of babies and even when combined with phe-nytoin the efficacy of these drugs together remains poor More worrying is the observation that phenobarbitone tends to reduce clinically evident seizures thereby giving the clinician a false sense of security whilst having little or no effect on the num-bers of electroconvulsive disorders This has been summarized appropriately as lsquoafter all these years we still love what doesnrsquot workrsquo19 Both midazolam and lidocaine infusions appear to be effective in abolishing severe seizures in some infants resistant to phenobarbitone Lidocaine should not be given to babies previ-ously exposed to phenytoin for fear of a synergistic adverse effect on cardiac rhythm
Do antiepileptic drugs cause brain damageA riskndashbenefit analysis is needed to evaluate the efficacy of anticonvulsants in stopping neonatal seizures which is poor with standard anticonvulsants as discussed above against the risk of administering the anticonvulsant drugs themselves Phenobarbitone has been reported to have adverse effects on the developing brain including inhibition of brain growth20 neuronal toxicity21 and adverse behavioural and cognitive effects into adult life when administered to young animals22 Phenytoin shows unpredictable plasma levels and potential cardiotoxicity
Recent studies have shown an effect of AED exposure on the developing brain by causing neurodegeneration23 Phenytoin administration to immature rat pups at doses which produce serum levels similar to those achieved in human neonates was associated with widespread neuronal death as a result of apop-tosis (programmed cell death) Phenobarbitone had a similar effect when a dosage regimen similar to 40 mgkg was used and
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
this effect was maximal in the more immature brain Diazepam and clonazepam also resulted in a similar effect Midazolam and lidocaine were not tested in this study The combination of phenobarbitone or phenytoin with diazepam had a particularly profound effect on neurodegeneration
In summary recent data suggest that the commonly used AEDs for neonatal convulsions may in themselves cause neuro-degeneration due to apoptosis with lasting effects on develop-ment Many babies with neonatal convulsions are treated with at least two AEDs and this may produce more severe adverse effects than the seizures themselves
Practical management of neonatal seizures
Assimilation of these data and formulation of a rational policy is difficult when faced with a fitting neonate on an intensive care unit and pressure on the medical staff to lsquodo somethingrsquo but it is important to accept that sometimes doing nothing is preferable to using potentially dangerous drugs in a situation which does not warrant such intervention Many babies who have normal interseizure neurological clinical findings and whose seizures are relatively brief and infrequent probably do not need anticon-vulsant medication A normal or near-normal background EEG trace should reassure the clinician that anticonvulsants can be withheld
Some causes of neonatal convulsions are treatable such as meningitis hypoglycaemia hypocalcaemia and inborn errors of metabolism and each baby should be rapidly and carefully investigated for cause of the convulsions
In some babies clinical assessment of seizures is difficult ie when the baby is very sick small or paralyzed Sometimes it may be difficult to assess the significance of certain movement pat-terns Under these circumstances an EEG may prove to be very helpful In many units EEG is not available out of hours and a simple aEEG or CFM is strongly advised Modern instruments are very simple to apply and prolonged or frequent seizures should be identified with only moderate training The printout can be faxed to a more senior doctor if there is doubt as to what is shown on the trace
The balance of knowledge now is that frequent seizures cause additional damage to the developing brain and that treatment to abolish the seizures is warranted Unfortunately there is little evidence that the majority of seizures can be effectively termi-nated by current standard therapy Furthermore it appears that the more abnormal the background EEG the more difficult it is to control the seizures Nevertheless a written protocol for the management of neonatal convulsions is required on each unit Phenobarbitone and phenytoin remain the mainstay of treat-ment although their effectiveness is disappointing There is little to suggest that midazolam is more effective than lidocaine as third-line therapy but lidocaine is precluded if phenytoin has been previously used
In view of the anxiety as to the neurodegenerative effects on the immature brain of most anticonvulsants used in the neonatal period (particularly when multiple drugs are used) it is prefer-able to use only one drug to maximum dosage before introduc-ing a second In addition the duration of anticonvulsants should be minimized and the drugs stopped at the earliest opportu-nity It is my practice to stop anticonvulsants prior to discharge
paeDiatRiCS anD CHilD HealtH 184 18
from hospital if the baby is neurologically normal on clinical examination
REFEREnCES
1 Ronen gm penney S andrews W the epidemiology of clinical
neonatal seizures in newfoundland a population-based study
J Pediatr 1999 134 71ndash75
2 lanska mJ lanska DJ Baumann RJ et al a population-based study
of neonatal seizures in Fayette County Kentucky Neurology 1995
45 724ndash732
3 Rennie Jm Chorley g Boylan gB et al non-expert use of the
cerebral function monitor for neonatal seizure detection Arch Dis
Child Fetal Neonatal Ed 2004 89 F37ndashF40
4 tekgul H gauvreau K Soul J et al the current etoliologic profile
and neurodevelopmental outcome of seizures in term newborn
infants Pediatrics 2006 117 1270ndash1280
5 Surtees R Wolf n treatable neonatal epilepsy Arch Dis Child 2007
92 659ndash661
6 Ben-ari y Holmes gl effects of seizures on developmental
processes in the immature brain Lancet Neurol 2006 5 1055ndash
1063
7 Holmes gl gairsa Jl Chevassus-au-louis n et al Consequences of
neonatal seizures in the rat morphological and behavioral effects
Ann Neurol 1998 44 845ndash857
8 Stafstrom Ce Chronopoulos a thurber S et al age-dependent
cognitive and behavioural deficits following kainic-acid inducing
seizures Epilepsia 1993 34 420ndash432
9 Schmid R tandon p Stafstrom Ce et al effects of neonatal seizures
on subsequent seizure-induced brain injury Neurology 1999 53
1754ndash1761
10 Hoffmann aF Zhao Q Holmes gl Cognitive impairment following
status epilepticus and recurrent seizures during early development
support for the ldquotwo-hit hypothesisrdquo Epilepsy Behav 2004 5
873ndash877
11 Wirrell eC armstrong ea osman lD et al prolonged seizures
exacerbate perinatal hypoxic-ischemic brain damage Pediatr Res
2001 50 445ndash454
12 Carmo KB Barr p Drug treatment of neonatal seizures by
neonatologists and paediatric neurologists J Paediatr Child Health
2005 41 313ndash316
13 Hall Rt Hall FK Daily DK High-dose phenobarbital therapy in term
newborn infants with severe perinatal asphyxia a randomized
prospective study with three-year follow-up J Pediatr 1998 132
345ndash348
14 Boylan gB Rennie Jm pressler Rm et al phenobarbitone neonatal
seizures and video-eeg Arch Dis Child Fetal Neonatal Ed 2002 86
F165ndash170
15 painter mJ Scher mS Stein aD et al phenobarbital compared with
phenytoin for the treatment of neonatal seizures N Engl J Med
1999 341 485ndash489
16 Singh D Kumar p narang a a randomized controlled trial of
phenobarbital in neonates with hypoxic ischemic encephalopathy
J Matern Fetal Neonatal Med 2005 18 391ndash395
17 Castro Conde JR Borges H Domenech martinez e et al midazolam
in neonatal seizures with no response to phenobarbital Neurology
2005 64 876ndash879
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
18 malingre mm Van Rooij lgm Rademaker Cma et al Development
of an optimal lidocaine infusion strategy for neonatal seizures Eur
J Pediatr 2006 165 598ndash604
19 Sankar R painter mJ neonatal seizures after all these years we still
love what doesnrsquot work Neurology 2005 64 776ndash777
20 Diaz J Schain J Bailey Bg phenobarbital-induced brain growth
retardation in artificially reared rat pups Biol Neonate 1977 32 77ndash82
21 mattson RH phenobarbital toxicity in levy RH Dreifuss Fe
mattson RH et al eds antiepipeptic Drugs 3rd edn new york
Raven 1985 p 341ndash355
22 mikati ma Holmes gl Chronopoulos a et al phenobarbital
modifies seizure-related brain injury in the developing brain Ann
Neurol 1994 36 425ndash453
23 Bittigau p Sifringer m genz K et al antiepileptic drugs and
apoptotic neurodegeneration in the developing brain Proc Natl
Acad Sci U S A 2002 99 15089ndash15094
paeDiatRiCS anD CHilD HealtH 184 182
Practice points
bull the clinician needs to be aware that almost any repetitive
stereotype movement pattern can be a manifestation of
neonatal seizures
bull eeg is important in defining neonatal seizures
bull Frequent short-lived seizures have been shown to cause long-
term neurodevelopmental problems
bull Conventional anticonvulsant medication is ineffective in
abolishing neonatal seizures in greater than 50 of cases
bull there is evidence that exposure of the neonatal brain to
multiple anticonvulsants causes neuronal death
bull Future research is needed to evaluate more effective
anticonvulsants for treating this condition
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
Emotional support for families of sick neonatesMarina nicolaou
cristine Glazebrook
AbstractParents of sick neonates experience high levels of stress anxiety and
depression Most interventions with families of sick infants have focused
on fostering the motherndashinfant relationship through the provision of
information about infant developmental needs or through increased
motherndashinfant contact Many of these studies have reported improved
maternal well-being though there are some concerns about the scope
and practicality of large-scale interventions The few studies to have
prioritized emotional support for parents of sick neonates have pro-
duced encouraging results even interventions requiring relatively few re-
sources such as telephone support parent-to-parent support and group
support have been associated with reduced psychological morbidity for
parents The needs of parents can change throughout their infantrsquos hos-
pitalization and not all want or benefit from the provision of additional
support Thus neonatal intensive care units should aim to provide a
varied flexible and sustainable programme of support options Further
research should focus on the needs of fathers
Keywords mental health neonatal intensive care parents
The admission of an infant to neonatal care is acknowledged to be a source of considerable distress for families This review aims to explore evidence for the psychological impact on families of having an infant in neonatal intensive care and to identify evi-dence for the effectiveness of interventions to promote parental well-being It will conclude with recommendations for strategies to support parents of vulnerable infants and suggestions for fur-ther research
Psychological impact of neonatal care for parents
The majority of research examining the effect on parents of having a sick neonate has focused on families of premature or low birthweight infants Such research has found that parents with a sick neonate exhibit high levels of stress compared to normative samples and to parents of healthy full-term infants1 Singer et al2 examined the stress experienced by mothers of high-risk very low birthweight (VLBW) low-risk VLBW and term
Marina Nicolaou MPhil is a Teaching Assistant at the School of
Community Health Sciences University of Nottingham Nottingham UK
Cristine Glazebrook PhD is a Professor of Health Psychology at the School
of Community Health Sciences University of Nottingham Nottingham UK
PaeDiaTrics anD cHilD HealTH 184 196
infants Several self-report measures were used including the Brief Symptom Inventory the Parenting Stress Index (PSI) the Impact on Family Scale and the Family Inventory of Life Events and Changes (FILE) Mothers of VLBW infants had more psycho-logical distress at 1 month compared to mothers of term infants Mothers of high-risk VLBW infants also reported high psycho-logical distress at 2 years and high levels of parenting stress at 3 years Mothers have also been found to have higher stress levels compared to fathers Shaw et al3 examined the prevalence of acute stress disorder (ASD) in 40 parents whose infants were in the neonatal intensive care unit (NICU) Nearly half of the moth-ers (44) met the criteria for ASD although none of the fathers did Furthermore the severity of the symptoms (measured by the number of concurrent symptoms) was greater for the moth-ers than for the fathers3 The reasons behind this difference have been widely speculated with some believing that it is due to the mothersrsquo greater psychological involvement with the infant as evidenced by their general greater vulnerability to postpartum psychological disorder It could also reflect gender differences in coping style
Having an infant who requires intensive medical care repre-sents a significant emotional burden for families Not only is there extreme anxiety surrounding the infantrsquos health and distress for the childrsquos suffering there is also the unfamiliar and intimidating environment of the NICU to adjust to Hopper in her review of the literature identified sources of stress for parents of sick neo-nates as falling into three areas4 Situational factors included the severity of the infantrsquos illness and how parents adapted to the life crisis of having a sick infant Personal factors involved parental emotions about their roles and the instrumental and informa-tional support which were available to them The third area was classified as environmental sources of stress and included the environment of the NICU and the relationship between parents and members of staff This relationship has been examined by several studies in the nursing literature nurses are seen as ide-ally placed to provide the necessary support and information to parents with sick neonates However whilst some studies have shown that supportive and helpful hospital staff can have a posi-tive effect on parents other studies have highlighted the prob-lems and difficulties which can manifest It has been shown that parents and nurses often have very different ideas about issues eg the necessary skills and competencies needed in an NICU or the characteristics that make a lsquogood motherrsquo
Research has shown that there may be a relationship between high levels of parental stress and an increased likelihood of depression5 Postpartum depression is a psychiatric illness which appears in 10ndash15 of postpartum women Its reported preva-lence rates however have ranged from less than 10 up to 306 depending on the instruments used the population exam-ined and the timing of the research Several factors have been found to be associated with postpartum depression including poor social support and infant-related stressors6 Evidence indi-cates that postnatal depression may be underreported and this is of concern since the mental and psychological health of the mother can affect her relationship with her infant and thus the infantrsquos cognitive and emotional development5 Depressed moth-ers appear to look touch and talk to their infants less frequently and also appear to show fewer positive and more negative faces7 The vocalizations of mothers suffering with depression have also
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
been found to be less effective at promoting cognitive growth and learning in infants8
If researchers are interested in finding ways of providing sup-port for families of sick neonates then they must listen to what such families perceive their needs to be in order to avoid increas-ing anxiety and distress Furthermore the provision of appropri-ate support be it emotional informational or social will enhance parental coping abilities increase self-esteem and reduce anxiety It should be noted though that the research conducted around these issues has often taken lsquosupport needsrsquo as being synony-mous with lsquoinformation needsrsquo Such studies have examined the type the amount and quality of information that parents receive and perceive themselves as needing but have not explored in equal depth the perceived emotional support needs of families who have a sick infant In addition the needs of parents may change throughout their infantrsquos illness Ward examined the per-ceived needs of 52 parents of infants in an NICU9 Parents rated the needs of their hospitalized infant as most important along with the need to be reassured Interestingly they ranked their support needs as least important This research was conducted during the first week of the infantsrsquo hospitalization however which would explain the preoccupation of the parents with the infantrsquos health These results demonstrate that if researchers want to find ways of providing emotional support to parents of sick neonates they must be prepared not only to listen to parents but also to be flexible enough to satisfy the parentsrsquo changing needs and expectations
Interventions aimed at supporting parents
Most interventions that been evaluated in controlled studies have focused on supporting the motherndashinfant relationship and provid-ing information on infant development Many of these interven-tions have included the aim of improving the parental emotional state and thus psychological outcomes such as stress or anxi-ety have been assessed However few studies appear to include fathers This means that strategies implemented to provide emo-tional support to families of sick neonates are often derived from interventions tailored for mothers even though fathers may have different emotional needs
A wide range of interventions with mothers and infants has been evaluated in the NICU Increasing motherndashinfant contact through kangaroo care has been found to reduce maternal anxiety1011 and educational programmes delivered to fami-lies in the NICU have also been associated with reduced emo-tional difficulties in parents12ndash14 Kaaresen and colleagues implemented an intervention which consisted of eight sessions before discharge and four home visits all by trained nurses The sample included 71 premature infants in the intervention group 69 premature infants in the control group and 74 infants in the full-term control group The randomized controlled trial found that the intervention reduced parenting stress in both mothers and fathers of premature infants compared to controls to a level equivalent to parents in the term control group13 At 6 months corrected age mothers of preterm infants who had not received the intervention had total PSI scores which were 17 points higher than the mothers of infants born at term (an effect size of 057) A similar study evaluated the efficacy of an educationalndashbehavioural programmendashCreating Opportunities for
PaeDiaTrics anD cHilD HealTH 184 19
Parent Empowerment (COPE) ndash through a randomized controlled trial with 260 families of premature infants14 COPE was a four-phase educationalndashbehavioural programme which began as early as 2ndash4 d after mothers had given birth and continued until 1 week after discharge from the NICU The programme consisted of audiotaped and written infant behaviour information along with photographs which focused on common behaviours and characteristics of premature infants It also included various par-ent activities in the form of a four-phase workbook which aimed to assist mothers in the implementation of the experimental infor-mation COPE was found significantly to reduce maternal stress in the NICU as well as maternal anxiety and depressive symptoms after hospitalization In contrast a cluster randomized trial of a parenting intervention delivered to mothers of very premature infants from soon after birth showed no benefits for parenting stress1 The authors hypothesized that the intervention had not been of sufficient intensity particularly in the weeks surrounding discharge Neonatal care presents a significant barrier to parent-ing in the early weeks following a very preterm birth and so inter-ventions which focus on the developmental needs of infants and the parentndashchild relationship should particularly aim to support parents as they take on the parenting role There was also concern that the intervention had failed to reach those most at risk
Since large-scale projects can be costly to implement and may often fail to reach the families in most need it may be wiser to focus on intervention programmes which are more practical and easier to implement within a neonatal care setting Research has shown that even interventions which are based on one-off meet-ings with parents of sick neonates can be effective Jotzo and Poets examined the effect of an intervention programme aimed at reducing the severity of traumatic responses as a result of giv-ing birth prematurely15 Their programme consisted of a one-off intervention meeting along with additional psychological help throughout the hospitalization of the infant The meeting cov-ered a variety of issues including a reconstruction of the events shortly before and after the infantrsquos birth relaxation techniques discussion of coping strategies available resources and social support and support during emotional outbursts The measures used included the Impact of Event Scale (IES) and the Peritrau-matic Dissociative Experience Questionnaire At discharge the mothers who received the intervention were found to have a significantly lower traumatic impact as a result of premature birth Furthermore fewer mothers in the intervention group showed symptoms of clinically significant psychological trauma at discharge compared to mothers in the control group (36 vs 76)15 The lsquoParents Circle Programrsquo is another intervention with a similar structure16 This consisted of a 90 min session for parents with the aim of enhancing the developing relationship between parents and infants and to offer parents support A total of 104 parents (59 mothers and 45 fathers) and 44 members of hospital staff were asked to evaluate the programme and their results were analysed using content analysis Families reported gaining perspective on their situation feeling supported becom-ing aware of cues and optimizing interactions and becoming aware of available resources Parents and staff alike felt that participating in the intervention helped parents overcome the difficulties associated with the early time of their infantrsquos hos-pitalization Additional studies have also found positive results with fairly minimal interventions including discussion groups
7 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
in the NICU music during kangaroo care and pairing mothers of sick neonates with trained mothers who had been through similar experiences
Parent support programmes
Parent support programmes (PSPs) which are based in NICUs can provide parents with the opportunity to talk to parents who have been in similar situations and also to discuss their emo-tions with professionals who can help them cope with their situa-tion111718 The parent-to-parent support programme for mothers of preterm infants evaluated by Preyde and Ardal included edu-cational parental support group meetings and individual par-ent-to-parent support (primarily telephone support)19 Measures used included the Parental Stressor Scale NICU the State and the Trait Anxiety Inventories and the Beck Depression Inven-tory After 4 months of participation mothers in the intervention group reported lower levels of stress state anxiety and depres-sion compared to control group mothers The authors speculated however that the participants who were able to meet face to face with other parents were those who benefited the most Hurst conducted a comprehensive survey of an NICU-based PSP This PSP was provided in a variety of formats including a weekly parent support group hospital visitation and 24-h telephone sup-port20 Of the 477 participants 303 families used the PSP dur-ing a 2-year evaluation period with 78 using only one form of support and 18 using two forms Of a sub-sample of 48 parents asked to complete an evaluation of the PSP 92 stated that they would recommend such a programme to other parents Furthermore the majority of parents felt that it made them feel supported and helped them deal with their emotions20 This is an indication that such programmes can be very successful in sup-porting parents throughout their infantrsquos hospitalization It also shows that it can be beneficial to give parents several options and formats when it comes to such support services It is impor-tant to consider though that both the Hurst and the Preyde and Ardal studies found that some participants did not find the sup-port programmes helpful even reporting that they had caused them increased stress and anxiety Therefore it should not be assumed that support programmes will suit every individual and will provide the required support for all parents1920 NICUs need to be flexible enough to provide parents with a range of forms of support to choose from
The increased understanding of the strains that parents of sick neonates have to deal with has also led to efforts to improve customary practices in NICUs Family-centred care focuses on infants and their needs and attempts to redefine the relationship between parents and caregivers These practices strive to provide parents with support during their infantrsquos illness by focusing on freely sharing information and on the collaboration between parents and hospital staff Family-centred care has been found to be associated with several beneficial outcomes including improved parental satisfaction increased parental comfort staff satisfaction and decreased parental stress18 Research is already examining these practices and questioning how these can be improved further Such research reflects the increasing effort focused on lsquohumanizingrsquo the environment in NICUs in order to make parents feel more comfortable about spending time with their infants
PaeDiaTrics anD cHilD HealTH 184 19
Conclusion
Surprisingly few interventions have prioritized the provision of emotional support for parents of sick neonates or accounted for the changing needs and wishes of parents over the course of their infantrsquos care Large-scale supportive education-based inter-ventions have been shown to be effective in reducing parental distress However the feasibility and sustainability of such pro-grammes should also be considered Programmes which require significant additional resources can be expensive and there are also issues of training and quality control Interventions which require significant input from parents may also place additional burdens on families making them potentially less accessible to those most at risk Arguably the aim should be to explore ways of providing acceptable and effective informational support which could be complemented by emotional support from health professionals and from other parents in the unit Increasingly studies are exploring the use of computers and multimedia as an engaging flexible and cost-effective method of targeting indi-vidual needs and providing support and information Such com-puter-based and interactive multimedia interventions have been found to be successful with a range of patient groups and could therefore be examined as a complementary method of providing informational support to families with sick neonates
REfEREnCEs
1 Glazebrook c Marlow n israel c et al randomised trial of a
parenting intervention during neonatal intensive care Arch Dis Child
Fetal Neonatal Ed 2007 92 F438ndash443
2 singer lT salvator a Guo s collin M lilien l Baley J Maternal
psychological distress and parenting stress after the birth of a very
low-birth-weight infant JAMA 1999 281 799ndash805
3 shaw rJ Deblois T ikuta l Ginzburg K Fleisher B Koopman c
acute stress disorder among parents of infants in the neonatal
intensive care nursery Psychosomatics 2006 47 206ndash212
4 Hopper a sources of stress for parents of a sick neonate a
literature review Pediatr Nurs 2000 30 29ndash32
5 Davis l edwards H Mohay H wollin J The impact of very
premature birth on the psychological health of mothers Early Hum
Dev 2003 73 61ndash70
6 Bernazzani O saucier J-F David H Borgeat F Psychosocial
predictors of depressive symptomatology level in postpartum
women J Affect Disord 1997 46 39ndash49
7 Field T infants of depressed mothers Infant Behav Dev 1995 18
1ndash13
8 Kaplan Ps Bachorowski J-a Zarlengo-strouse P child-directed
speech produced by mothers with symptoms of depression fails
to promote associative learning in 4-month-old infants Child Dev
1999 70 560ndash570
9 ward K Perceived needs of parents of critically ill infants in
a neonatal intensive care unit (nicU) Pediatr Nurs 2001 27
281ndash286
10 lai Hl chen cJ Peng Tc et al randomized controlled trial of music
during kangaroo care on maternal state anxiety and preterm infantsrsquo
responses Int J Nurs Stud 2006 43 139ndash146
8 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
11 Tallandini Ma scalembra c Kangaroo mother care and mother-
premature infant dyadic interaction Infant Ment Health J 2006 27
251ndash275
12 Ohgi s Fukuda M akiyama T Gima H effect of an early intervention
programme on low birthweight infants with cerebral injuries
J Paediatr Child Health 2004 40 689ndash695
13 Kaaresen Pi ronning Ja Ulvund se Dahl lB a randomized
controlled trial of the effectiveness of an early-intervention program
in reducing parenting stress after preterm birth Pediatrics 2006
118 e9ndash19
14 Melnyk BM Feinstein nF alpert-Gillis l et al reducing premature
infantsrsquo length of stay and improving parentsrsquo mental health
outcomes with the creating opportunities for parent empowerment
(cOPe) neonatal intensive care unit program a randomized
controlled trial Pediatrics 2006 118 e1414ndash1427
15 Jotzo M Poets cF Helping parents cope with the trauma of
premature birth an evaluation of a trauma-preventive psychological
intervention Pediatrics 2005 115 915ndash919
16 Pearson J andersen K evaluation of a program to promote positive
parenting in the neonatal intensive care unit Neonatal Netw 2001
20 43ndash48
17 roman l lindsay J Boger r et al Parent-to-parent support
initiated in the neonatal intensive care unit Res Nurs Health 1995
18 385ndash394
18 Meyer ec coll cTG lester BM Boukydis cFZ McDonough sM Oh w
Family-based intervention improves maternal psychological well-
being and feeding interaction of preterm infants Pediatrics 1994
93 241ndash246
PaeDiaTrics anD cHilD HealTH 184 19
19 Preyde M ardal F effectiveness of a parent ldquobuddyrdquo program for
mothers of very preterm infants in a neonatal intensive care unit
CMAJ 2003 168 969ndash973
20 Hurst i One size does not fit all Parentsrsquo evaluations of a support
program in a newborn intensive care nursery J Perinat Neonatal
Nurs 2006 20 252ndash261
Practice points
bull Parents of sick neonates experience significant distress and
exhibit higher levels of stress anxiety and depression than
parents of healthy infants
bull educational support emotional support and increased
motherndashinfant contact have been shown to promote maternal
well-being
bull emotional support for fathers has been largely neglected in
the research literature
bull Parents benefit from a choice of supportive facilities which
could include face-to-face sessions with health professionals
telephone support hospital visitation parent-to-parent
support and unit-based group support meetings
bull Parentsrsquo support needs can change during their infantrsquos
hospitalization and not all parents want or benefit from the
provision of additional information and emotional support in
the neonatal unit
9 copy 2008 elsevier ltd all rights reserved
Personal Practice
When should enteral feeds be started in preterm infantsnicholas D embleton
AbstractPaediatricians are regularly faced with the question of when best to start
enteral feeds in preterm infants this is important as longer term out-
come may be compromised by sub-optimal nutrition in early life clinical
factors that may affect the decision to start and the risk and benefits
are discussed
Keywords breast milk feeding nutrition parenteral nutrition
Key points in the history
Alice is lsquonutritionally vulnerablersquo and whilst this may not be immediately apparent it will affect her long term outcome Her energy stores are extremely limited and consist primarily of pro-tein She has less than 5 fat and little energy associated with stored glycogen She is losing about 1 gkgd protein equivalent so she needs at least that and a minimum of 50ndash60 kcalkg of energy just to maintain the status quo let alone grow
Her weight is on the 25th centile Review of any antenatal his-tory may reveal whether fetal growth was normal Fetal growth retardation can occur with a weight greater than 10th centile The presence of antenatal absent or reversed end diastolic flow in the umbilical artery indicates poor gut blood flow This increases the risk of necrotizing enterocolitis (NEC) and might suggest a more cautious approach to starting feeds1
She has no important cardiovascular problems but if she were hypotensive gut blood flow may be low There is no umbilical
Nicholas D Embleton BSC (Hons) MBBS (Hons) MD FRCPCH is Consultant in
Neonatal Medicine at Newcastle Neonatal Service Royal Victoria
Infirmary Newcastle upon Tyne NE1 4LP UK
Should you start feeds at a day of age
alice was born following spontaneous labour at 30 weeksrsquo
gestation she weighed 1300 g and is now 18 h old she was
briefly ventilated and then extubated to continuous positive
airway pressure 12 h ago in 35 oxygen she has had caffeine
citrate but still has intermittent episodes of self-correcting
apnoea she was commenced on iv 10 dextrose but this was
replaced by a parenteral amino acid solution (referred to as
lsquotPnrsquo) along with intralipid at 0900 this morning serum glucose
is 11 mmoll and blood pressure is 42 systolic
PaeDiatrics anD cHilD HealtH 184 20
arterial catheter in situ but there is no good evidence that this should delay the decision to start feeds Her glucose is high but this is quite common in a baby like this Could this be a sign of sepsis Caffeine does not affect the incidence of NEC2 The great-est risk factor for NEC in this case is prematurity
What else might be found on examination
Up until 24 h ago she was swallowing large amounts of amniotic fluid What will have changed since then
General examination should confirm peripheral perfusion lsquogestaltrsquo view (does she look lsquowellrsquo) and cardiovascular status lsquoBowel soundsrsquo are not usually helpful
The most important variable likely to affect gut perfusion is the arterial duct Precordial lsquoheaversquo and a loud murmur are sug-gestive but it is possible to have a significant ductal shunt in a baby with a normal examination Cardiac ultrasound will con-firm this diagnosis It might be better to treat a large shunt first with indometacin and to delay starting feeds for a further 24 h
It is not possible to assess gut perfusion clinically but normal perfusion elsewhere (adequate urine output usually indicates adequate renal perfusion) would be reassuring Most preterm babies have a few abdominal lsquoloopsrsquo visible but a distended abdomen with many palpable loops suggests ileus This might be secondary to sepsis or poor gut blood flow Preterm babies do not pass much meconium in the first 24ndash48 h
Balance of risks between starting and withholding feeds
Alice requires 35ndash4 gkgd of protein and 120 kcalkgd to grow3 This will initially be provided parenterally Delaying feeds increases the risk of gut villous atrophy and prolongs the need for lsquototal parenteral nutrition (TPN)rsquo TPN requires intravenous access and so increases the risk of sepsis and when prolonged use is required combined with the lack of enteral feeding may result in hepatic impairment
Delaying feeds may allow a gut that has been chronically under-perfused to re-establish more normal perfusion although normal gut endocrine function digestive enzyme upregulation and motility require a source of intraluminal nutrients1 A recent study suggested benefit from delaying the introduction of feeds4 but methodologi-cal problems exist5 Although a Cochrane meta-analysis suggested no benefit only two studies were included6 A large UK-based trial is examining the effect of early or late feeding in preterm infants who were born growth retarded following identification of antena-tal absent or reversed end diastolic flow in the umbilical artery7
When starting feeds what volume should be used
There are no good data to guide this decision We start with 24 mlkg (1 mlkgh) and then increase by this amount each day Most babies achieve full enteral feeds (ge150 mlkgd) by a week of age Feeding guidelines improve the outcome8 Measure-ment or assessment of gastric aspirates is not consistently useful in predicting subsequent feeding intolerance or development of NEC Aspirate volumes equivalent to or sometimes greater than the amount given in the preceding 1ndash2 h are usually normal Most aspirates have a greenish colour Thick bloody or intensely bile-stained aspirates require detailed assessment
0 copy 2008 elsevier ltd all rights reserved
Personal Practice
What else affects decisions and outcome
Feeding success is affected by sepsis and NEC Scrupulous atten-tion should be paid to hand washing and intravenous access and blood sampling should be minimized There is no good evidence to support the routine use of pro-kinetic agents or H2 blockers
The most important clinical intervention affecting the occur-rence of NEC is the use of breast milk9 All efforts should be directed at persuading parents of the benefits and supporting the process Some clinicians delay starting feeds for a further 24 h whilst expressed breast milk becomes available Donor breast milk might be equally efficacious10
RefeRenceS
1 Dorling J Kempley s leaf a Feeding growth restricted preterm
infants with abnormal antenatal Doppler results Arch Dis Child Fetal
Neonatal Ed 2005 90 F359ndash363
2 schmidt B roberts rs Davis P et al caffeine therapy for apnea of
prematurity N Engl J Med 2006 354 2112ndash2121
PaeDiatrics anD cHilD HealtH 184 20
3 embleton nD Pang n cooke rJ Postnatal malnutrition and growth
retardation an inevitable consequence of current recommendations
in preterm infants Pediatrics 2001 107 270ndash273
4 Berseth cl Bisquera Ja Paje VU Prolonging small feeding volumes
early in life decreases the incidence of necrotizing enterocolitis in
very low birth weight infants Pediatrics 2003 111 529ndash534
5 Menon G Boyle eM embleton nD et al introduction of enteral
feeds in preterm infants Pediatrics 2004 114 327ndash328
6 Kennedy Ka tyson Je chamnanvanikij s early versus delayed
initiation of progressive enteral feedings for parenterally fed low
birth weight or preterm infants Cochrane Database Syst Rev 2000
cD001970
7 wwwnpeuoxacukadept
8 Patole sK de Klerk n impact of standardised feeding regimens on
incidence of neonatal necrotising enterocolitis a systematic review
and meta-analysis of observational studies Arch Dis Child Fetal
Neonatal Ed 2005 90 F147ndash151
9 lucas a cole tJ Breast milk and neonatal necrotising enterocolitis
Lancet 1990 336 1519ndash1523
10 Boyd ca Quigley Ma Brocklehurst P Donor breast milk versus
infant formula for preterm infants systematic review and meta-
analysis Arch Dis Child Fetal Neonatal Ed 2007 92 F169ndash175
1 copy 2008 elsevier ltd all rights reserved
self-assessment
Case 1A term male infant born to consanguineous parents is assessed at 24 h of age due to poor feeding profuse yellow watery diar-rhoea and irritability He weighed 32 kg at birth and delivery was uneventful There was no polyhydramnios He has been breastfed since birth On examination he is pale with a non-tender but distended abdomen and reduced bowel sounds His weight is 275 kg and he looks dehydrated Examination is otherwise normal
Initial investigations (normal values in parentheses) showed
sodium 149 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 65 mmollitre (25ndash75)
creatinine 147 μmollitre (40ndash110)
chloride 119 mmollitre (95ndash105)
haemoglobin 172 gdl (140ndash200)
White blood cell count 80 times 109litre (100ndash260)
Platelet count 302 times 109litre (150ndash400)
arterial blood gas
ph 720 (730ndash745)
PcO2 23 kPa (46ndash60)
Bicarbonate 68 mmollitre (220ndash260)
Base excess minus186 mmollitre (minus20 to +20)
lactate 59 mmollitre (06ndash24)
An abdominal X-ray shows distended bowel loops with no intramural thickening or pneumoperitoneum (Figure 1)
He was given nil by mouth and received intravenous fluids and antibiotics His dehydration improved but the metabolic acidosis and diarrhoea persisted despite receiving no enteral feeds and the commencement of total parenteral nutrition Blood and stool cultures were negative
1 Which of the following best describes these results Choose ONE answer ONLY from the followingA Hypernatraemia hyperchloraemic metabolic acidosis
with increased anion gapB Hypernatraemia hyperchloraemic metabolic acidosis
with normal anion gap
Manish Sadarangani BM BCh MA MRCPCH is Clinical Research Fellow
at the Department of Paediatrics University of Oxford Centre for
Clinical Vaccinology and Tropical Medicine Churchill Hospital
Oxford OX3 7LJ UK
Shabna Rajapaksa MB BChir MA MRCPCH is Specialist Registrar in
Paediatrics at the Paediatric Intensive Care Unit John Radcliffe
Hospital Oxford OX3 9DU UK
Nicholas Mann MD FRCP FRCPCH DCH is Consultant Paediatrician at the
Department of Paediatrics Royal Berkshire Hospital Reading RG1
5AN UK
self-assessment
C Hypernatraemic dehydration and compensated metabolic acidosis
D Acute renal failureE Renal tubular acidosis
2 What is the likely diagnosis Choose ONE answer ONLY from the followingA Hirschsprung disease ndash long segmentB Cystic fibrosis with meconium ileusC Microvillus inclusion diseaseD Cowrsquos milk protein intoleranceE Lactose intolerance
3 What is the investigation of choice Choose ONE answer ONLY from the followingA Rectal biopsy with staining for acetylcholine receptorsB Immunoreactive trypsinC Gastrointestinal endoscopy and biopsyD Stool microscopy and cultureE Stool reducing substances
Case 2A 4-year-old boy presents with a 3 d history of jaundice and a florid rash He has had orange urine and there is no change in his stool colour His family originate from Kosovo and have lived in the UK for the last 8 years He has never left the UK There is no history of blood transfusion or sex-ual abuse The grandmother was recently diagnosed with hepatitis B
On examination he is well apyrexial and mildly jaundiced with cervical and axillary lymphadenopathy He has an exten-sive papular rash over the face extremities and trunk (Figure 2) There is 3 cm hepatomegaly with no splenomegaly or ascites Examination is otherwise normal
Figure 1 abdominal X-ray of baby
Paediatrics and child health 184 202 copy 2008 elsevier ltd all rights reserved
self-assessment
Initial investigations are as follows
haemoglobin 110 gdl (113ndash135)
White blood cell count 108 times 109litre (50ndash150)
Platelet count 278 times 109litre (150ndash400)
inr 10 (08ndash12)
aPt ratio 10 (08ndash13)
sodium 140 mmollitre (135ndash145)
Potassium 42 mmollitre (35ndash50)
Urea 56 mmollitre (25ndash75)
creatinine 65 μmollitre (45ndash120)
total bilirubin 66 μmollitre (0ndash15)
conjugated bilirubin 23 μmollitre (0ndash10)
alanine aminotransferase (alt) 2033 iUlitre (0ndash35)
alkaline phosphatase 987 iUlitre (71ndash234)
Gamma-glutamyl transferase (GGt) 870 iUlitre (0ndash51)
1 What is the name of this rash Choose ONE answer ONLY from the followingA Erythema multiformeB Erythema migransC GianottiminusCrosti syndromeD EczemaE Dermatitis herpetiformis
2 What is the most likely diagnosis Choose ONE Answer ONLY from the followingA Autoimmune hepatitisB Hepatitis BC Hepatitis DD Wilson diseaseE Alpha-1 antitrypsin deficiency
3 What is the best means of management Choose ONE answer ONLY from the followingA Isolation until the jaundice disappearsB ImmunosuppressionC Copper chelating agents and genetic counsellingD Patient and family education with consideration of
antiviral agentsE Liver transplantation
Case 3A 10-month-old boy presents with 3 weeks of vomiting and constipation ndash he is passing hard stools every 2ndash3 days He has fallen from the 9th to below the 04th centile in the last 6 weeks He passed meconium within the first 24 h of life On examina-tion he looks pale and there are some dysmorphic features ndash a short nose long philtrum and wide mouth He has normal heart sounds with a grade 3 ejection systolic murmur loudest at the upper right sternal edge Examination is otherwise normal
Initial investigations are as follows
haemoglobin 91 gdl (113ndash141)
total white blood cell count 124 times 109litre (60ndash170)
Platelet count 407 times 109litre (150ndash400)
sodium 144 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 78 mmollitre (25ndash75)
creatinine 78 μmollitre (45ndash120)
albumin 52 glitre (35ndash50)
corrected calcium 384 mmollitre (238ndash263)
Phosphate 167 mmollitre (099ndash157)
1 What is the most likely diagnosis Choose ONE answer ONLY from the followingA HyperparathyroidismB Acute leukaemiaC Williams syndromeD Hypervitaminosis DE Familial hypocalciuric hypercalcaemia
2 Which investigation would be most useful in establishing the diagnosis Choose ONE answer ONLY from the followingA Intact parathyroid hormone assayB Blood filmC Fluorescent in-situ hybridization for 7q1123 deletionD 25-hydroxyvitamin D assayE Urine calciumcreatinine ratio
3 Which of the following treatments would not be suitable for this patient Choose ONE answer ONLY from the followingA Low calcium dietB Normal saline infusionC FurosemideD CorticosteroidsE Bisphosphonates
Case 4A 10-week-old girl presents with a 2-day history of poor feed-ing Her mother has been concerned about weakness since birth She only has a flicker of movement in the arms none in the legs and has a weak cry She has been passing urine and opening her bowels normally She was born at full term by normal delivery and did not require any resuscitation at birth Normal fetal movements were felt antenatally and there was no polyhydramnios She is the first child of non- consanguineous parents and there is no significant family his-tory On examination she is alert and fixing and following appropriately She has a weak cry and a weak suck There is reduced central and peripheral tone with marked head lag
Figure 2 rash found on examination
Paediatrics and child health 184 203 copy 2008 elsevier ltd all rights reserved
self-assessment
Muscle power is grade 3 out of 5 in the arms and legs There is no muscle or tongue fasciculation and she has absent reflexes throughout The remainder of the examination is normal
Electromyogram shows irregular polyphasic motor unit potentials with marked instability consistent with a dener-vating and re-innervating process (Figure 3)
1 Which of the following additional investigations may be helpful Choose ONE answer ONLY from the followingA Nerve conduction studiesB Creatine kinase assayC Muscle biopsyD SMN1 gene analysisE All of the above
2 What is the most likely cause of this childrsquos symptoms Choose ONE answer ONLY from the followingA Congenital myotonic dystrophyB Duchenne muscular dystrophyC PraderminusWilli syndromeD Spinal muscular atrophyE Mitochondrial myopathy
3 What is the mode of inheritance of this disease Choose ONE answer ONLY from the followingA X-linked recessiveB Autosomal recessiveC Autosomal dominantD MitochondrialE Sporadic
Case 5A 13-year-old girl presents with a 3-week history of fever up to 40degC night sweats and headache She has a reduced appetite with some weight loss She has no other specific symptoms She was on holiday in China 7 months ago On examination she looks well and has a temperature of 387degC There is no lymphadenopathy and no rashes Examination is entirely normal
Results of investigations are as follows
haemoglobin 126 gdl (120ndash160)
total white blood cell count 132 times 109litre (43ndash108)
neutrophil count 115 times 109litre (25ndash75)
Platelet count 244 times 109litre (150ndash400)
Blood film neutrophilia with left shift
erythrocyte sedimentation rate 63 mmh (1ndash20)
c-reactive protein 219 mglitre (0ndash5)
Blood culture Streptococcus intermedius
from anaerobic bottle only
csf culture negative
Magnetic resonance imaging (MRI) of the brain shows acute frontal sinusitis with a large intracranial frontal extra-dural empyema (Figure 4)
1 Which of the following would be appropriate management Choose ONE answer ONLY from the followingA A 12-week course of intravenous antibioticsB Drainage of the frontal sinus followed by 2 weeks of
intravenous antibioticsC Drainage of the empyema followed by 2 weeks of
intravenous antibioticsD Drainage of the empyema and the frontal sinus
followed by 2 weeks of oral antibiotics
1151
1152
1153
1154
1155
1156
1157
1158
1159
1200
50ms 1mV
Figure 3 electromyogram recording from the patient Figure 4 Parasagittal section from mri scan of patient
Paediatrics and child health 184 204 copy 2008 elsevier ltd all rights reserved
self-assessment
E Drainage of the empyema and the frontal sinus followed by 8 weeks of intravenous antibiotics
2 Streptococcus intermedius is a potential pathogen in which of the following infections Choose ONE answer ONLY from the followingA Liver abscessB Urinary tract infectionC MeningitisD Thoracic empyemaE Pneumonia
3 Which of the following statements regarding lsquopyrexia of unknown originrsquo in children is false Choose ONE answer ONLY from the followingA Malignancy is the underlying pathology in 5ndash15 of
casesB An aetiology will be found in over 90 of casesC The most common cause is infectionD A rheumatological cause is found in 10ndash20 of casesE Familial Mediterranean fever can occur in children of
non-Mediterranean ethnicity
Answers
Case 11 AThe anion gap is a useful tool to differentiate the causes of a metabolic acidosis It is calculated by the equation
Anion gap = [Na K ] [Cl HCO ]3+ + minus minus+ minus +
It represents the effect of unmeasured anions on the plasma pH and is normally 10ndash18 mmollitre
2 CMicrovillus inclusion disease is a severe autosomal recessive enteropathy that is typically apparent within hours or days after birth It is the second most common cause of protracted diarrhoea in the newborn after infectious causes It is characterized by severe yellow watery diarrhoea and malabsorption due to hypoplasia andor atrophy of the villi of the small intestine secondary to an inherited defect in the brush border membrane This results in severe dehydration malnutrition and metabolic acidosis due to bicarbonate loss from the gut
3 CDiagnosis of microvillus inclusion disease is made on small bowel biopsy Electron microscopy findings are of intracellular brush border inclusions and densely packed apical cytoplasmic vesicular bodies indicating microvillous atrophy There is no cure Treatment is supportive with total parenteral nutrition and consideration of small bowel transplantation
Further reAding
Goulet O ruemmele f causes and management of intestinal failure
in children Gastroenterology 2006 130(suppl 1) s16ndash28
rhoads Jm Vogler rc lacey sr et al microvillus inclusion disease
In vitro jejunal electrolyte transport Gastroenterology 1991
100 811ndash817
Case 21 CGianottindashCrosti syndrome is a distinct self-limiting rash commonly associated with viral infections in children between 2 and 6 years of age It presents as multiple pink to redminusbrown papules or papulovesicles which may be pruritic and can become confluent Gianotti and Crosti initially described the exanthema as associated with hepatitis B virus and they termed it papular acrodermatitis of childhood It can occur in several viral diseases eg hepatitis A B and C coxsackie viruses and cytomegalovirus
2 BHepatitis is a syndrome characterized by inflammation or injury of liver cells which may develop into cell necrosis and subsequently fibrosis andor cirrhosis Biochemically there are raised liver enzymes The degree of transaminase elevation does not correlate with the severity of the disease process Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of viral hepatitis
3 DHepatitis B infection is transmitted via blood sexually or vertically Infection may be acute or chronic Diagnostic markers are the presence of surface antigen (HBsAg) and HBV DNA The presence of e antigen (HBeAg) indicates high infectivity Infected newborns have a 95 risk of becoming carriers this risk decreases with infection acquired later in childhood Approximately 15ndash25 of HBV carriers will die from cirrhosis or hepatocellular carcinoma Extrahepatic findings are more common in older children and include membranous glomerulonephritis and GianottiminusCrosti syndrome Fulminant hepatic failure occurs in severe cases resulting in persistent jaundice encephalopathy and coagulopathy Management includes counselling family members monitoring for ongoing liver disease and consideration of antiviral therapy
Further reAding
Brandt O abeck d Gianotti r Burgdorf W Gianotti crosti
syndrome J Am Acad Dermatol 2006 54 136ndash145
slowik mK Jhaveri r hepatitis B and c viruses in infants and
young children Semin Pediatr Infect Dis 2005 16 296ndash305
Case 31 CHypercalcaemia is uncommon in infancy The most common symptoms in this age group are irritability vomiting and constipation It may be a manifestation of Williams syndrome vitamin D or calcium excess as well as disorders associated with reduced bone formation such as hypophosphatasia or increased bone resorption such as malignancy Occasionally
Paediatrics and child health 184 205 copy 2008 elsevier ltd all rights reserved
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-
SympoSium neonatology
21 Carlo Wa Stark aR Wright ll et al minimal ventilation to prevent
bronchopulmonary dysplasia in extremely-low-birth-weight infants
J Pediatr 2002 141 370ndash374
22 okumura a Hayakawa F Kato t et al Hypocarbia in preterm
infants with periventricular leukomalacia the relation between
hypocarbia and mechanical ventilation Pediatrics 2001 107
469ndash475
23 peters o Ryan S matthew l Cheng K lunn J Randomised
controlled trial of acetate in preterm neonates receiving parenteral
nutrition Arch Dis Child 1997 77 F12ndash15
24 yildizda D yapiciolu H yilmaz Hl Sertdemir y Correlation of
simultaneously obtained capillary venous and arterial blood gases
of patients in a paediatric intensive care unit Arch Dis Child 2004
89 176ndash180
25 aliwalas ll noble l nesbitt K et al agreement of carbon
dioxide levels measured by arterial transcutaneous and end tidal
methods in preterm infants 28 weeks gestation J Perinatol 2005
25 26ndash29
26 Hagerty JJ Kleinman me Zurakowski D et al accuracy of a new
low-flow sidestream capnography technology in newborns a pilot
study J Perinatol 2002 22 219ndash225
paeDiatRiCS anD CHilD HealtH 184 17
27 poets CF Wilken m Seidenberg J Southall Dp von der Hardt H
Reliability of a pulse oximeter in the detection of hyperoxemia
J Pediatr 1993 122 87ndash90
Practice points
bull a stable extracellular pH is important for optimal cellular
functioning
bull abnormalities in acidndashbase balance are regulated by buffer
systems and the respiratory and renal tract
bull maintaining a stable pH is challenging for newborn babies
due to their high rates of acid production and immature
regulatory mechanisms
bull arterial or capillary blood gases provide an effective way to
monitor acidndashbase balance in newborns
bull Blood gases should be analysed in a structured manner
assessing pH and then respiratory and metabolic components
bull the treatment of acidndashbase abnormalities should be directed
at the underlying problem not merely at correcting pH
7 copy 2007 elsevier ltd all rights reserved
SympoSium neonatology
Recognition and management of neonatal seizuresmalcolm levene
AbstractSeizures are the most common major manifestation of central nervous
system dysfunction in the newborn there are many causes but perina-
tal asphyxia and haemorrhagicinfarction lesions account for about 75
there is now considerable evidence that frequent but short seizures in
the neonate affect subsequent neurodevelopmental outcome Studies
using eeg or modified continuous tracing of eeg activity (aeeg or CFm)
have shown that there is often electroconvulsive dissociation this re-
fers to poor correlation between electrical seizures and clinical seizures
Commonly used anticonvulsants appear to increase electroconvulsive
dissociation effective management of neonatal seizures has proved very
disappointing and less than 50 of seizures are abolished by first-line
anticonvulsant medication (phenobarbitone or phenytoin) Drugs such
as midazolam and lidocaine may further reduce seizures but require
more evaluation the challenge is to assess new and more effective anti-
convulsants which are themselves associated with little neurotoxicity
Keywords antiepileptic drugs eeg neonatal seizures neurodegeneration
Convulsions are the most common major neurological sign seen in newborn infants and their incidence estimated from large population studies is 26 per 1000 live births1 Premature infants are over four times more likely to have convulsions than full-term infants12 Neonatal status epilepticus (continuous seizure activity lasting 30 min or more) diagnosed clinically is rare and accounts for only 5 of infants with seizures1 although this is now recognized more frequently as the result of continuous EEG monitoring3
Neonatal convulsions are described as presenting in a num-ber of different ways and various seizure types can be seen in the same baby over a number of hours The frequencies of the various patterns of seizure activity are given in Table 1 In very premature babies and to a lesser extent in term infants minor movement abnormalities may be difficult to identify as subtle seizures These include lip smacking tongue thrusting mouth-ing pedalling type movements of the lower limbs or swimming movements of the arms Apnoea can be a common manifesta-tion of subtle seizures The signs can be protean and vary from baby to baby or even in the same baby Virtually any stereotypic
Malcolm Levene MD FMedSc FRCPCH FRCH is Professor and Head of
Department of Paediatrics and Child Health at University of Leeds Leeds
and Honorary Neonatologist at Leeds General Infirmary Leeds UK
paeDiatRiCS anD CHilD HealtH 184 178
movement may be a manifestation of a seizure disorder in the newborn
Aetiology
The more carefully the fitting baby is investigated the more likely it is that a cause for the seizures will be found A number of recent papers have described the aetiology of neonatal con-vulsions after extensive investigations14 Tekgul et al4 recently studied a consecutive group of full-term infants with evidence of neonatal convulsions (recognized both clinically and on EEG) and reported their outcome Table 2 summarizes these data as well as risk of moderate or severe disability for each causative factor Perinatal asphyxia is the commonest cause for convul-sions in term infants with haemorrhagic or ischaemic lesions also being common
Overall the prognosis for the group of term babies with con-vulsions was good 72 had a favourable outcome Where asphyxia (hypoxicndashischaemic insult) is the cause of neonatal convulsions the outcome is poor in 50 The prognosis for neonatal convulsions when they were due to arterial or cere-brovenous infarction or intracranial haemorrhage was generally good Individually inborn errors are a very rare cause of neo-natal convulsions but in view of the treatable nature of some of these it is essential that these be considered and investigated appropriately5
Patterns of seizure activity in the newborn
Movement pattern Frequency ()
Clonic 50
tonic 20
Subtle 10ndash35 depending on maturity
myoclonic 5
Table 1
Cause incidence and outcome of neonatal convulsions in term infants14
Aetiological factor Incidence () Poor outcome ()
asphyxia 38ndash40 50
Cerebral arteriovenous
infarction
20 0
intracranial haemorrhage 12ndash20 13
Congenital cerebral anomaly 5ndash10 100
Hypoglycaemiahypocalcaemia 3ndash19
infection 3ndash20
inborn error of metabolism 1
unknown cause 10ndash13 0
Refers to moderate and severe neurodevelopmental abnormalitynumbers too small to make meaningful predictions
Table 2
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Controversies in the clinical management of neonatal seizures
In recent years we have learnt much more about the neurobi-ology of seizures and their effect on the developing brain The neonatal brain is in a neurophysiologically hyperexcitable state compared to the more mature brain and therefore is more prone to seizure activity This is due largely to a relative excess of GABA neuroreceptors GABA receptors are usually inhibitory but in the immature brain they have a paradoxically excitatory effect This changes at about term in primates and with progressive develop-ment they adopt a neuroinhibitory role6
The propensity to seizures in the neonatal brain makes resolv-ing the balance of risks between continuing seizure activity on the one hand against potentially adverse effects of therapy on the other a very important equation Added to this is the problem of accurately diagnosing neonatal seizures and whether commonly used anticonvulsants are successful in controlling them
These conundrums can be posed as a series of challenging questions which are discussed below
Do neonatal convulsions cause brain injuryConvulsions are a sign of neurological compromise and may indi-cate significant underlying structural brain damage or biochemi-cal disturbance which may cause further brain damage in its own right There has been considerable debate about the scale of the disability that convulsions cause the immature brain over and above that due to the underlying cause Most of our knowledge comes from studies in rodents and these have provided some tentative answers to this question
Seizures in the mature brain lead to neuronal necrosis but studies in very young rat pups whose brain development is somewhat similar to full-term infants have shown that a series of five brief seizures on five successive days does not cause struc-tural neuronal damage but does produce morphological changes in hippocampal neurones and worryingly deficits in the rat learning and visual spatial memory function in adolescent and adult life7 A single prolonged neonatal convulsion in similarly immature rats does not produce any functional effects8 Others have shown that following priming of the neonatal rat brain by short seizures as described above a further insult comprising induction of status epilepticus in the same rats at an older age causes neuronal necrosis9 This has been referred to as the lsquotwo hit hypothesisrsquo10
A more specific question is does seizure activity in an already significantly compromised brain cause additional neuropathol-ogy Wirrell et al11 studied a series of immature rat pups with the induction of an hypoxicndashischaemic (asphyxial) insult fol-lowed by either chemically-induced fits or a control sham pro-cedure In the more severely asphyxiated animals the degree of brain damage was increased significantly in those that had the additional burden of induced seizures
In summary these studies show that the immature brain is more resistant to short frequent post-seizure damage than the mature brain but despite resulting in no loss of neuronal numbers the function of the brain is permanently affected in later life In the asphyxiated brain seizures appear to have an additional adverse effect on brain damage Furthermore the immature brain that has been lsquoprimedrsquo by early seizures is more
paeDiatRiCS anD CHilD HealtH 184 179
vulnerable to status epilepticus later in life It would appear from these data that frequent seizures in the human infant should be stopped and this begs the question as to whether currently used anticonvulsants effectively control neonatal seizures
Can we rely on clinical versus EEG diagnosis of neonatal convulsionsTraditionally the diagnosis of neonatal convulsions has been made by observation and description of the frequency of abnor-mal movements EEG has been technically difficult in the hostile electrical activity of a neonatal intensive care environment and considerable expertise is required for analysis of the trace It is usually not practical to undertake traditional EEG recordings at the time the baby shows abnormal movements More recently various technological developments have allowed more direct investigation of neuronal electrical activity by either video-EEG or compressed recording of the amplitude integrated EEG (aEEG or CFM)
Rennie et al3 at Kingrsquos College Hospital London have under-taken extensive evaluation of video-EEG and have found that this technique detects many convulsions not recognized by a single channel aEEG or CFM trace Of 19 infants with evidence of convulsions on EEG only four were recognized on CFM but this may have been due to the observersrsquo lack of experi-ence with this technique In other centres that have developed appropriate expertise aEEG or CFM has proved more sensitive to the detection of seizures Video-EEG studies have also shown that many movements interpreted by experienced clinicians to be seizures are not associated with abnormal cortical activity Conversely many electrical seizures are not associated with abnormal movements This is referred to as electroconvulsive dissociation
In summary clinical observation alone to detect the fitting baby is unreliable in that it may either over-detect seizure activ-ity which is not present on EEG or under-detect clinical seizures in infants with EEG-proven convulsions The decision as to which babies to treat with antiepileptic drugs therefore becomes somewhat arbitrary
Do anticonvulsants stop neonatal seizuresAlthough neonatal seizures are common there are few random-ized controlled trials assessing the benefits of antiepileptic drugs (AEDs) in the treatment of this condition Phenobarbitone is the most widely used first-line AED and in an Australasian study 95 of neonatologists and paediatric neurologists used this drug as first-line management12 The most commonly used loading dosage is 20 mgkg but regimens of up to 40 mgkg have been recommended (Table 3)13 Four trials have evaluated the effect of phenobarbitone in abolishing neonatal seizures Two of these studies used EEG to monitor response to the drug1415 and one compared phenobarbitone with phenytoin15 In the latter study seizures were completely controlled in only 43 of babies and in the group where phenytoin was the first drug used com-plete seizure control was achieved in 45 This study switched babies from their first AED to the other if complete control was not obtained on EEG monitoring after exposure to first-line therapy In babies who had been given phenobarbitone as first-line therapy seizure control was only achieved in 57 after phenytoin was added In those given phenytoin first complete
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Dosage regimens for first- second- and third-line anticonvulsants in the neonatal period
Loading dose Second loading dose if first
unsuccessfulMaintenance dose
phenobarbitone 20 mgkg by slow iv injection 10 mgkg iv 25ndash5 mgkg od
phenytoin 20 mgkg iv over 20 min not recommended
midazolam 150ndash200 μgkg iv infusion 1 μgkgmin iv infusion increasing to 5 μgkgmin
until favourable response
lidocaine 2 mgkg iv over 10 min 6 mgkgh for 6 h iv then 4 mgkgh for 12 h then
2 mgkgh for 12 h
lorazepam 005ndash01 mgkg by slow iv injection
Diazepam 03ndash04 mgkg iv over 3ndash5 min
lidocaine should not be used if the infant has previously been treated with phenytoin
Table 3
seizure control was achieved with the adding of phenobarbitone in 62
Boylan et al14 assessed the efficacy of phenobarbitone (20ndash40 mgkg iv over 20 min) in 14 babies monitored by video-EEG in only four was there complete abolition of seizures and in the other 10 electroconvulsive seizure activity increased whereas clinical evidence of seizures reduced This has been termed elec-troclinical dissociation and anticonvulsant drug use in the new-born appears to increase this feature They also showed that the babies least likely to respond to the first-line AED are those with the most abnormal background EEG
Two studies have evaluated the use of phenobarbitone in babies who had sustained significant asphyxial insult at birth Hall et al13 compared high-dose phenobarbitone (mean 39 mgkg) versus standard dose (27 mgkg) and reported fewer convul-sions and a significant reduction of severe disability or death in the high dose group (RR 030 CI 010ndash093) A recent study from India16 of babies with hypoxicndashischaemic encephalopathy ran-domized 25 babies to phenobarbitone (20 mgkg loading dose) and compared them with 20 control babies Only 2 of 25 (4) in the phenobarbitone group developed convulsions compared with 8 of 20 (40) in the control group (p = 001) Because of the specific enrolment criteria (asphyxial insult) neither of these studies is strictly comparable to the studies by Painter et al15 and Boylan et al14 whose intention was to assess the efficacy of first-line anticonvulsant therapy on convulsions of any cause diagnosed either clinically or by EEG
Other anticonvulsants used as second- and third-line drugs have been subject to few studies in the newborn Midazolam is administered as a bolus followed by continuous infusion A recent study17 has shown that in 10 of 13 neonates given intravenous midazolam for status epilepticus control of electri-cal seizures was achieved within the first hour of treatment having been previously shown to be refractory to phenobarbi-tone treatment Some of these babies required a second bolus infusion of midazolam to obtain control of all electrographic seizures
In some parts of Europe lidocaine is used as a third-line anti-convulsant Malingre et al18 evaluated 20 infants refractory to
paeDiatRiCS anD CHilD HealtH 184 180
both phenobarbitone and midazolam and who were then given lidocaine by continuous infusion Lidocaine was effective in abolishing electroconvulsive seizures diagnosed by aEEG in 76 of the treatment courses studied No babies developed cardiac arrhythmias a previously reported complication of lidocaine in older patients As a result of pharmacokinetic studies the dosage regimen has been modified (see Table 3)
In summary phenobarbitone is effective in seizure control in less than 50 of babies and even when combined with phe-nytoin the efficacy of these drugs together remains poor More worrying is the observation that phenobarbitone tends to reduce clinically evident seizures thereby giving the clinician a false sense of security whilst having little or no effect on the num-bers of electroconvulsive disorders This has been summarized appropriately as lsquoafter all these years we still love what doesnrsquot workrsquo19 Both midazolam and lidocaine infusions appear to be effective in abolishing severe seizures in some infants resistant to phenobarbitone Lidocaine should not be given to babies previ-ously exposed to phenytoin for fear of a synergistic adverse effect on cardiac rhythm
Do antiepileptic drugs cause brain damageA riskndashbenefit analysis is needed to evaluate the efficacy of anticonvulsants in stopping neonatal seizures which is poor with standard anticonvulsants as discussed above against the risk of administering the anticonvulsant drugs themselves Phenobarbitone has been reported to have adverse effects on the developing brain including inhibition of brain growth20 neuronal toxicity21 and adverse behavioural and cognitive effects into adult life when administered to young animals22 Phenytoin shows unpredictable plasma levels and potential cardiotoxicity
Recent studies have shown an effect of AED exposure on the developing brain by causing neurodegeneration23 Phenytoin administration to immature rat pups at doses which produce serum levels similar to those achieved in human neonates was associated with widespread neuronal death as a result of apop-tosis (programmed cell death) Phenobarbitone had a similar effect when a dosage regimen similar to 40 mgkg was used and
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
this effect was maximal in the more immature brain Diazepam and clonazepam also resulted in a similar effect Midazolam and lidocaine were not tested in this study The combination of phenobarbitone or phenytoin with diazepam had a particularly profound effect on neurodegeneration
In summary recent data suggest that the commonly used AEDs for neonatal convulsions may in themselves cause neuro-degeneration due to apoptosis with lasting effects on develop-ment Many babies with neonatal convulsions are treated with at least two AEDs and this may produce more severe adverse effects than the seizures themselves
Practical management of neonatal seizures
Assimilation of these data and formulation of a rational policy is difficult when faced with a fitting neonate on an intensive care unit and pressure on the medical staff to lsquodo somethingrsquo but it is important to accept that sometimes doing nothing is preferable to using potentially dangerous drugs in a situation which does not warrant such intervention Many babies who have normal interseizure neurological clinical findings and whose seizures are relatively brief and infrequent probably do not need anticon-vulsant medication A normal or near-normal background EEG trace should reassure the clinician that anticonvulsants can be withheld
Some causes of neonatal convulsions are treatable such as meningitis hypoglycaemia hypocalcaemia and inborn errors of metabolism and each baby should be rapidly and carefully investigated for cause of the convulsions
In some babies clinical assessment of seizures is difficult ie when the baby is very sick small or paralyzed Sometimes it may be difficult to assess the significance of certain movement pat-terns Under these circumstances an EEG may prove to be very helpful In many units EEG is not available out of hours and a simple aEEG or CFM is strongly advised Modern instruments are very simple to apply and prolonged or frequent seizures should be identified with only moderate training The printout can be faxed to a more senior doctor if there is doubt as to what is shown on the trace
The balance of knowledge now is that frequent seizures cause additional damage to the developing brain and that treatment to abolish the seizures is warranted Unfortunately there is little evidence that the majority of seizures can be effectively termi-nated by current standard therapy Furthermore it appears that the more abnormal the background EEG the more difficult it is to control the seizures Nevertheless a written protocol for the management of neonatal convulsions is required on each unit Phenobarbitone and phenytoin remain the mainstay of treat-ment although their effectiveness is disappointing There is little to suggest that midazolam is more effective than lidocaine as third-line therapy but lidocaine is precluded if phenytoin has been previously used
In view of the anxiety as to the neurodegenerative effects on the immature brain of most anticonvulsants used in the neonatal period (particularly when multiple drugs are used) it is prefer-able to use only one drug to maximum dosage before introduc-ing a second In addition the duration of anticonvulsants should be minimized and the drugs stopped at the earliest opportu-nity It is my practice to stop anticonvulsants prior to discharge
paeDiatRiCS anD CHilD HealtH 184 18
from hospital if the baby is neurologically normal on clinical examination
REFEREnCES
1 Ronen gm penney S andrews W the epidemiology of clinical
neonatal seizures in newfoundland a population-based study
J Pediatr 1999 134 71ndash75
2 lanska mJ lanska DJ Baumann RJ et al a population-based study
of neonatal seizures in Fayette County Kentucky Neurology 1995
45 724ndash732
3 Rennie Jm Chorley g Boylan gB et al non-expert use of the
cerebral function monitor for neonatal seizure detection Arch Dis
Child Fetal Neonatal Ed 2004 89 F37ndashF40
4 tekgul H gauvreau K Soul J et al the current etoliologic profile
and neurodevelopmental outcome of seizures in term newborn
infants Pediatrics 2006 117 1270ndash1280
5 Surtees R Wolf n treatable neonatal epilepsy Arch Dis Child 2007
92 659ndash661
6 Ben-ari y Holmes gl effects of seizures on developmental
processes in the immature brain Lancet Neurol 2006 5 1055ndash
1063
7 Holmes gl gairsa Jl Chevassus-au-louis n et al Consequences of
neonatal seizures in the rat morphological and behavioral effects
Ann Neurol 1998 44 845ndash857
8 Stafstrom Ce Chronopoulos a thurber S et al age-dependent
cognitive and behavioural deficits following kainic-acid inducing
seizures Epilepsia 1993 34 420ndash432
9 Schmid R tandon p Stafstrom Ce et al effects of neonatal seizures
on subsequent seizure-induced brain injury Neurology 1999 53
1754ndash1761
10 Hoffmann aF Zhao Q Holmes gl Cognitive impairment following
status epilepticus and recurrent seizures during early development
support for the ldquotwo-hit hypothesisrdquo Epilepsy Behav 2004 5
873ndash877
11 Wirrell eC armstrong ea osman lD et al prolonged seizures
exacerbate perinatal hypoxic-ischemic brain damage Pediatr Res
2001 50 445ndash454
12 Carmo KB Barr p Drug treatment of neonatal seizures by
neonatologists and paediatric neurologists J Paediatr Child Health
2005 41 313ndash316
13 Hall Rt Hall FK Daily DK High-dose phenobarbital therapy in term
newborn infants with severe perinatal asphyxia a randomized
prospective study with three-year follow-up J Pediatr 1998 132
345ndash348
14 Boylan gB Rennie Jm pressler Rm et al phenobarbitone neonatal
seizures and video-eeg Arch Dis Child Fetal Neonatal Ed 2002 86
F165ndash170
15 painter mJ Scher mS Stein aD et al phenobarbital compared with
phenytoin for the treatment of neonatal seizures N Engl J Med
1999 341 485ndash489
16 Singh D Kumar p narang a a randomized controlled trial of
phenobarbital in neonates with hypoxic ischemic encephalopathy
J Matern Fetal Neonatal Med 2005 18 391ndash395
17 Castro Conde JR Borges H Domenech martinez e et al midazolam
in neonatal seizures with no response to phenobarbital Neurology
2005 64 876ndash879
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
18 malingre mm Van Rooij lgm Rademaker Cma et al Development
of an optimal lidocaine infusion strategy for neonatal seizures Eur
J Pediatr 2006 165 598ndash604
19 Sankar R painter mJ neonatal seizures after all these years we still
love what doesnrsquot work Neurology 2005 64 776ndash777
20 Diaz J Schain J Bailey Bg phenobarbital-induced brain growth
retardation in artificially reared rat pups Biol Neonate 1977 32 77ndash82
21 mattson RH phenobarbital toxicity in levy RH Dreifuss Fe
mattson RH et al eds antiepipeptic Drugs 3rd edn new york
Raven 1985 p 341ndash355
22 mikati ma Holmes gl Chronopoulos a et al phenobarbital
modifies seizure-related brain injury in the developing brain Ann
Neurol 1994 36 425ndash453
23 Bittigau p Sifringer m genz K et al antiepileptic drugs and
apoptotic neurodegeneration in the developing brain Proc Natl
Acad Sci U S A 2002 99 15089ndash15094
paeDiatRiCS anD CHilD HealtH 184 182
Practice points
bull the clinician needs to be aware that almost any repetitive
stereotype movement pattern can be a manifestation of
neonatal seizures
bull eeg is important in defining neonatal seizures
bull Frequent short-lived seizures have been shown to cause long-
term neurodevelopmental problems
bull Conventional anticonvulsant medication is ineffective in
abolishing neonatal seizures in greater than 50 of cases
bull there is evidence that exposure of the neonatal brain to
multiple anticonvulsants causes neuronal death
bull Future research is needed to evaluate more effective
anticonvulsants for treating this condition
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
Emotional support for families of sick neonatesMarina nicolaou
cristine Glazebrook
AbstractParents of sick neonates experience high levels of stress anxiety and
depression Most interventions with families of sick infants have focused
on fostering the motherndashinfant relationship through the provision of
information about infant developmental needs or through increased
motherndashinfant contact Many of these studies have reported improved
maternal well-being though there are some concerns about the scope
and practicality of large-scale interventions The few studies to have
prioritized emotional support for parents of sick neonates have pro-
duced encouraging results even interventions requiring relatively few re-
sources such as telephone support parent-to-parent support and group
support have been associated with reduced psychological morbidity for
parents The needs of parents can change throughout their infantrsquos hos-
pitalization and not all want or benefit from the provision of additional
support Thus neonatal intensive care units should aim to provide a
varied flexible and sustainable programme of support options Further
research should focus on the needs of fathers
Keywords mental health neonatal intensive care parents
The admission of an infant to neonatal care is acknowledged to be a source of considerable distress for families This review aims to explore evidence for the psychological impact on families of having an infant in neonatal intensive care and to identify evi-dence for the effectiveness of interventions to promote parental well-being It will conclude with recommendations for strategies to support parents of vulnerable infants and suggestions for fur-ther research
Psychological impact of neonatal care for parents
The majority of research examining the effect on parents of having a sick neonate has focused on families of premature or low birthweight infants Such research has found that parents with a sick neonate exhibit high levels of stress compared to normative samples and to parents of healthy full-term infants1 Singer et al2 examined the stress experienced by mothers of high-risk very low birthweight (VLBW) low-risk VLBW and term
Marina Nicolaou MPhil is a Teaching Assistant at the School of
Community Health Sciences University of Nottingham Nottingham UK
Cristine Glazebrook PhD is a Professor of Health Psychology at the School
of Community Health Sciences University of Nottingham Nottingham UK
PaeDiaTrics anD cHilD HealTH 184 196
infants Several self-report measures were used including the Brief Symptom Inventory the Parenting Stress Index (PSI) the Impact on Family Scale and the Family Inventory of Life Events and Changes (FILE) Mothers of VLBW infants had more psycho-logical distress at 1 month compared to mothers of term infants Mothers of high-risk VLBW infants also reported high psycho-logical distress at 2 years and high levels of parenting stress at 3 years Mothers have also been found to have higher stress levels compared to fathers Shaw et al3 examined the prevalence of acute stress disorder (ASD) in 40 parents whose infants were in the neonatal intensive care unit (NICU) Nearly half of the moth-ers (44) met the criteria for ASD although none of the fathers did Furthermore the severity of the symptoms (measured by the number of concurrent symptoms) was greater for the moth-ers than for the fathers3 The reasons behind this difference have been widely speculated with some believing that it is due to the mothersrsquo greater psychological involvement with the infant as evidenced by their general greater vulnerability to postpartum psychological disorder It could also reflect gender differences in coping style
Having an infant who requires intensive medical care repre-sents a significant emotional burden for families Not only is there extreme anxiety surrounding the infantrsquos health and distress for the childrsquos suffering there is also the unfamiliar and intimidating environment of the NICU to adjust to Hopper in her review of the literature identified sources of stress for parents of sick neo-nates as falling into three areas4 Situational factors included the severity of the infantrsquos illness and how parents adapted to the life crisis of having a sick infant Personal factors involved parental emotions about their roles and the instrumental and informa-tional support which were available to them The third area was classified as environmental sources of stress and included the environment of the NICU and the relationship between parents and members of staff This relationship has been examined by several studies in the nursing literature nurses are seen as ide-ally placed to provide the necessary support and information to parents with sick neonates However whilst some studies have shown that supportive and helpful hospital staff can have a posi-tive effect on parents other studies have highlighted the prob-lems and difficulties which can manifest It has been shown that parents and nurses often have very different ideas about issues eg the necessary skills and competencies needed in an NICU or the characteristics that make a lsquogood motherrsquo
Research has shown that there may be a relationship between high levels of parental stress and an increased likelihood of depression5 Postpartum depression is a psychiatric illness which appears in 10ndash15 of postpartum women Its reported preva-lence rates however have ranged from less than 10 up to 306 depending on the instruments used the population exam-ined and the timing of the research Several factors have been found to be associated with postpartum depression including poor social support and infant-related stressors6 Evidence indi-cates that postnatal depression may be underreported and this is of concern since the mental and psychological health of the mother can affect her relationship with her infant and thus the infantrsquos cognitive and emotional development5 Depressed moth-ers appear to look touch and talk to their infants less frequently and also appear to show fewer positive and more negative faces7 The vocalizations of mothers suffering with depression have also
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
been found to be less effective at promoting cognitive growth and learning in infants8
If researchers are interested in finding ways of providing sup-port for families of sick neonates then they must listen to what such families perceive their needs to be in order to avoid increas-ing anxiety and distress Furthermore the provision of appropri-ate support be it emotional informational or social will enhance parental coping abilities increase self-esteem and reduce anxiety It should be noted though that the research conducted around these issues has often taken lsquosupport needsrsquo as being synony-mous with lsquoinformation needsrsquo Such studies have examined the type the amount and quality of information that parents receive and perceive themselves as needing but have not explored in equal depth the perceived emotional support needs of families who have a sick infant In addition the needs of parents may change throughout their infantrsquos illness Ward examined the per-ceived needs of 52 parents of infants in an NICU9 Parents rated the needs of their hospitalized infant as most important along with the need to be reassured Interestingly they ranked their support needs as least important This research was conducted during the first week of the infantsrsquo hospitalization however which would explain the preoccupation of the parents with the infantrsquos health These results demonstrate that if researchers want to find ways of providing emotional support to parents of sick neonates they must be prepared not only to listen to parents but also to be flexible enough to satisfy the parentsrsquo changing needs and expectations
Interventions aimed at supporting parents
Most interventions that been evaluated in controlled studies have focused on supporting the motherndashinfant relationship and provid-ing information on infant development Many of these interven-tions have included the aim of improving the parental emotional state and thus psychological outcomes such as stress or anxi-ety have been assessed However few studies appear to include fathers This means that strategies implemented to provide emo-tional support to families of sick neonates are often derived from interventions tailored for mothers even though fathers may have different emotional needs
A wide range of interventions with mothers and infants has been evaluated in the NICU Increasing motherndashinfant contact through kangaroo care has been found to reduce maternal anxiety1011 and educational programmes delivered to fami-lies in the NICU have also been associated with reduced emo-tional difficulties in parents12ndash14 Kaaresen and colleagues implemented an intervention which consisted of eight sessions before discharge and four home visits all by trained nurses The sample included 71 premature infants in the intervention group 69 premature infants in the control group and 74 infants in the full-term control group The randomized controlled trial found that the intervention reduced parenting stress in both mothers and fathers of premature infants compared to controls to a level equivalent to parents in the term control group13 At 6 months corrected age mothers of preterm infants who had not received the intervention had total PSI scores which were 17 points higher than the mothers of infants born at term (an effect size of 057) A similar study evaluated the efficacy of an educationalndashbehavioural programmendashCreating Opportunities for
PaeDiaTrics anD cHilD HealTH 184 19
Parent Empowerment (COPE) ndash through a randomized controlled trial with 260 families of premature infants14 COPE was a four-phase educationalndashbehavioural programme which began as early as 2ndash4 d after mothers had given birth and continued until 1 week after discharge from the NICU The programme consisted of audiotaped and written infant behaviour information along with photographs which focused on common behaviours and characteristics of premature infants It also included various par-ent activities in the form of a four-phase workbook which aimed to assist mothers in the implementation of the experimental infor-mation COPE was found significantly to reduce maternal stress in the NICU as well as maternal anxiety and depressive symptoms after hospitalization In contrast a cluster randomized trial of a parenting intervention delivered to mothers of very premature infants from soon after birth showed no benefits for parenting stress1 The authors hypothesized that the intervention had not been of sufficient intensity particularly in the weeks surrounding discharge Neonatal care presents a significant barrier to parent-ing in the early weeks following a very preterm birth and so inter-ventions which focus on the developmental needs of infants and the parentndashchild relationship should particularly aim to support parents as they take on the parenting role There was also concern that the intervention had failed to reach those most at risk
Since large-scale projects can be costly to implement and may often fail to reach the families in most need it may be wiser to focus on intervention programmes which are more practical and easier to implement within a neonatal care setting Research has shown that even interventions which are based on one-off meet-ings with parents of sick neonates can be effective Jotzo and Poets examined the effect of an intervention programme aimed at reducing the severity of traumatic responses as a result of giv-ing birth prematurely15 Their programme consisted of a one-off intervention meeting along with additional psychological help throughout the hospitalization of the infant The meeting cov-ered a variety of issues including a reconstruction of the events shortly before and after the infantrsquos birth relaxation techniques discussion of coping strategies available resources and social support and support during emotional outbursts The measures used included the Impact of Event Scale (IES) and the Peritrau-matic Dissociative Experience Questionnaire At discharge the mothers who received the intervention were found to have a significantly lower traumatic impact as a result of premature birth Furthermore fewer mothers in the intervention group showed symptoms of clinically significant psychological trauma at discharge compared to mothers in the control group (36 vs 76)15 The lsquoParents Circle Programrsquo is another intervention with a similar structure16 This consisted of a 90 min session for parents with the aim of enhancing the developing relationship between parents and infants and to offer parents support A total of 104 parents (59 mothers and 45 fathers) and 44 members of hospital staff were asked to evaluate the programme and their results were analysed using content analysis Families reported gaining perspective on their situation feeling supported becom-ing aware of cues and optimizing interactions and becoming aware of available resources Parents and staff alike felt that participating in the intervention helped parents overcome the difficulties associated with the early time of their infantrsquos hos-pitalization Additional studies have also found positive results with fairly minimal interventions including discussion groups
7 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
in the NICU music during kangaroo care and pairing mothers of sick neonates with trained mothers who had been through similar experiences
Parent support programmes
Parent support programmes (PSPs) which are based in NICUs can provide parents with the opportunity to talk to parents who have been in similar situations and also to discuss their emo-tions with professionals who can help them cope with their situa-tion111718 The parent-to-parent support programme for mothers of preterm infants evaluated by Preyde and Ardal included edu-cational parental support group meetings and individual par-ent-to-parent support (primarily telephone support)19 Measures used included the Parental Stressor Scale NICU the State and the Trait Anxiety Inventories and the Beck Depression Inven-tory After 4 months of participation mothers in the intervention group reported lower levels of stress state anxiety and depres-sion compared to control group mothers The authors speculated however that the participants who were able to meet face to face with other parents were those who benefited the most Hurst conducted a comprehensive survey of an NICU-based PSP This PSP was provided in a variety of formats including a weekly parent support group hospital visitation and 24-h telephone sup-port20 Of the 477 participants 303 families used the PSP dur-ing a 2-year evaluation period with 78 using only one form of support and 18 using two forms Of a sub-sample of 48 parents asked to complete an evaluation of the PSP 92 stated that they would recommend such a programme to other parents Furthermore the majority of parents felt that it made them feel supported and helped them deal with their emotions20 This is an indication that such programmes can be very successful in sup-porting parents throughout their infantrsquos hospitalization It also shows that it can be beneficial to give parents several options and formats when it comes to such support services It is impor-tant to consider though that both the Hurst and the Preyde and Ardal studies found that some participants did not find the sup-port programmes helpful even reporting that they had caused them increased stress and anxiety Therefore it should not be assumed that support programmes will suit every individual and will provide the required support for all parents1920 NICUs need to be flexible enough to provide parents with a range of forms of support to choose from
The increased understanding of the strains that parents of sick neonates have to deal with has also led to efforts to improve customary practices in NICUs Family-centred care focuses on infants and their needs and attempts to redefine the relationship between parents and caregivers These practices strive to provide parents with support during their infantrsquos illness by focusing on freely sharing information and on the collaboration between parents and hospital staff Family-centred care has been found to be associated with several beneficial outcomes including improved parental satisfaction increased parental comfort staff satisfaction and decreased parental stress18 Research is already examining these practices and questioning how these can be improved further Such research reflects the increasing effort focused on lsquohumanizingrsquo the environment in NICUs in order to make parents feel more comfortable about spending time with their infants
PaeDiaTrics anD cHilD HealTH 184 19
Conclusion
Surprisingly few interventions have prioritized the provision of emotional support for parents of sick neonates or accounted for the changing needs and wishes of parents over the course of their infantrsquos care Large-scale supportive education-based inter-ventions have been shown to be effective in reducing parental distress However the feasibility and sustainability of such pro-grammes should also be considered Programmes which require significant additional resources can be expensive and there are also issues of training and quality control Interventions which require significant input from parents may also place additional burdens on families making them potentially less accessible to those most at risk Arguably the aim should be to explore ways of providing acceptable and effective informational support which could be complemented by emotional support from health professionals and from other parents in the unit Increasingly studies are exploring the use of computers and multimedia as an engaging flexible and cost-effective method of targeting indi-vidual needs and providing support and information Such com-puter-based and interactive multimedia interventions have been found to be successful with a range of patient groups and could therefore be examined as a complementary method of providing informational support to families with sick neonates
REfEREnCEs
1 Glazebrook c Marlow n israel c et al randomised trial of a
parenting intervention during neonatal intensive care Arch Dis Child
Fetal Neonatal Ed 2007 92 F438ndash443
2 singer lT salvator a Guo s collin M lilien l Baley J Maternal
psychological distress and parenting stress after the birth of a very
low-birth-weight infant JAMA 1999 281 799ndash805
3 shaw rJ Deblois T ikuta l Ginzburg K Fleisher B Koopman c
acute stress disorder among parents of infants in the neonatal
intensive care nursery Psychosomatics 2006 47 206ndash212
4 Hopper a sources of stress for parents of a sick neonate a
literature review Pediatr Nurs 2000 30 29ndash32
5 Davis l edwards H Mohay H wollin J The impact of very
premature birth on the psychological health of mothers Early Hum
Dev 2003 73 61ndash70
6 Bernazzani O saucier J-F David H Borgeat F Psychosocial
predictors of depressive symptomatology level in postpartum
women J Affect Disord 1997 46 39ndash49
7 Field T infants of depressed mothers Infant Behav Dev 1995 18
1ndash13
8 Kaplan Ps Bachorowski J-a Zarlengo-strouse P child-directed
speech produced by mothers with symptoms of depression fails
to promote associative learning in 4-month-old infants Child Dev
1999 70 560ndash570
9 ward K Perceived needs of parents of critically ill infants in
a neonatal intensive care unit (nicU) Pediatr Nurs 2001 27
281ndash286
10 lai Hl chen cJ Peng Tc et al randomized controlled trial of music
during kangaroo care on maternal state anxiety and preterm infantsrsquo
responses Int J Nurs Stud 2006 43 139ndash146
8 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
11 Tallandini Ma scalembra c Kangaroo mother care and mother-
premature infant dyadic interaction Infant Ment Health J 2006 27
251ndash275
12 Ohgi s Fukuda M akiyama T Gima H effect of an early intervention
programme on low birthweight infants with cerebral injuries
J Paediatr Child Health 2004 40 689ndash695
13 Kaaresen Pi ronning Ja Ulvund se Dahl lB a randomized
controlled trial of the effectiveness of an early-intervention program
in reducing parenting stress after preterm birth Pediatrics 2006
118 e9ndash19
14 Melnyk BM Feinstein nF alpert-Gillis l et al reducing premature
infantsrsquo length of stay and improving parentsrsquo mental health
outcomes with the creating opportunities for parent empowerment
(cOPe) neonatal intensive care unit program a randomized
controlled trial Pediatrics 2006 118 e1414ndash1427
15 Jotzo M Poets cF Helping parents cope with the trauma of
premature birth an evaluation of a trauma-preventive psychological
intervention Pediatrics 2005 115 915ndash919
16 Pearson J andersen K evaluation of a program to promote positive
parenting in the neonatal intensive care unit Neonatal Netw 2001
20 43ndash48
17 roman l lindsay J Boger r et al Parent-to-parent support
initiated in the neonatal intensive care unit Res Nurs Health 1995
18 385ndash394
18 Meyer ec coll cTG lester BM Boukydis cFZ McDonough sM Oh w
Family-based intervention improves maternal psychological well-
being and feeding interaction of preterm infants Pediatrics 1994
93 241ndash246
PaeDiaTrics anD cHilD HealTH 184 19
19 Preyde M ardal F effectiveness of a parent ldquobuddyrdquo program for
mothers of very preterm infants in a neonatal intensive care unit
CMAJ 2003 168 969ndash973
20 Hurst i One size does not fit all Parentsrsquo evaluations of a support
program in a newborn intensive care nursery J Perinat Neonatal
Nurs 2006 20 252ndash261
Practice points
bull Parents of sick neonates experience significant distress and
exhibit higher levels of stress anxiety and depression than
parents of healthy infants
bull educational support emotional support and increased
motherndashinfant contact have been shown to promote maternal
well-being
bull emotional support for fathers has been largely neglected in
the research literature
bull Parents benefit from a choice of supportive facilities which
could include face-to-face sessions with health professionals
telephone support hospital visitation parent-to-parent
support and unit-based group support meetings
bull Parentsrsquo support needs can change during their infantrsquos
hospitalization and not all parents want or benefit from the
provision of additional information and emotional support in
the neonatal unit
9 copy 2008 elsevier ltd all rights reserved
Personal Practice
When should enteral feeds be started in preterm infantsnicholas D embleton
AbstractPaediatricians are regularly faced with the question of when best to start
enteral feeds in preterm infants this is important as longer term out-
come may be compromised by sub-optimal nutrition in early life clinical
factors that may affect the decision to start and the risk and benefits
are discussed
Keywords breast milk feeding nutrition parenteral nutrition
Key points in the history
Alice is lsquonutritionally vulnerablersquo and whilst this may not be immediately apparent it will affect her long term outcome Her energy stores are extremely limited and consist primarily of pro-tein She has less than 5 fat and little energy associated with stored glycogen She is losing about 1 gkgd protein equivalent so she needs at least that and a minimum of 50ndash60 kcalkg of energy just to maintain the status quo let alone grow
Her weight is on the 25th centile Review of any antenatal his-tory may reveal whether fetal growth was normal Fetal growth retardation can occur with a weight greater than 10th centile The presence of antenatal absent or reversed end diastolic flow in the umbilical artery indicates poor gut blood flow This increases the risk of necrotizing enterocolitis (NEC) and might suggest a more cautious approach to starting feeds1
She has no important cardiovascular problems but if she were hypotensive gut blood flow may be low There is no umbilical
Nicholas D Embleton BSC (Hons) MBBS (Hons) MD FRCPCH is Consultant in
Neonatal Medicine at Newcastle Neonatal Service Royal Victoria
Infirmary Newcastle upon Tyne NE1 4LP UK
Should you start feeds at a day of age
alice was born following spontaneous labour at 30 weeksrsquo
gestation she weighed 1300 g and is now 18 h old she was
briefly ventilated and then extubated to continuous positive
airway pressure 12 h ago in 35 oxygen she has had caffeine
citrate but still has intermittent episodes of self-correcting
apnoea she was commenced on iv 10 dextrose but this was
replaced by a parenteral amino acid solution (referred to as
lsquotPnrsquo) along with intralipid at 0900 this morning serum glucose
is 11 mmoll and blood pressure is 42 systolic
PaeDiatrics anD cHilD HealtH 184 20
arterial catheter in situ but there is no good evidence that this should delay the decision to start feeds Her glucose is high but this is quite common in a baby like this Could this be a sign of sepsis Caffeine does not affect the incidence of NEC2 The great-est risk factor for NEC in this case is prematurity
What else might be found on examination
Up until 24 h ago she was swallowing large amounts of amniotic fluid What will have changed since then
General examination should confirm peripheral perfusion lsquogestaltrsquo view (does she look lsquowellrsquo) and cardiovascular status lsquoBowel soundsrsquo are not usually helpful
The most important variable likely to affect gut perfusion is the arterial duct Precordial lsquoheaversquo and a loud murmur are sug-gestive but it is possible to have a significant ductal shunt in a baby with a normal examination Cardiac ultrasound will con-firm this diagnosis It might be better to treat a large shunt first with indometacin and to delay starting feeds for a further 24 h
It is not possible to assess gut perfusion clinically but normal perfusion elsewhere (adequate urine output usually indicates adequate renal perfusion) would be reassuring Most preterm babies have a few abdominal lsquoloopsrsquo visible but a distended abdomen with many palpable loops suggests ileus This might be secondary to sepsis or poor gut blood flow Preterm babies do not pass much meconium in the first 24ndash48 h
Balance of risks between starting and withholding feeds
Alice requires 35ndash4 gkgd of protein and 120 kcalkgd to grow3 This will initially be provided parenterally Delaying feeds increases the risk of gut villous atrophy and prolongs the need for lsquototal parenteral nutrition (TPN)rsquo TPN requires intravenous access and so increases the risk of sepsis and when prolonged use is required combined with the lack of enteral feeding may result in hepatic impairment
Delaying feeds may allow a gut that has been chronically under-perfused to re-establish more normal perfusion although normal gut endocrine function digestive enzyme upregulation and motility require a source of intraluminal nutrients1 A recent study suggested benefit from delaying the introduction of feeds4 but methodologi-cal problems exist5 Although a Cochrane meta-analysis suggested no benefit only two studies were included6 A large UK-based trial is examining the effect of early or late feeding in preterm infants who were born growth retarded following identification of antena-tal absent or reversed end diastolic flow in the umbilical artery7
When starting feeds what volume should be used
There are no good data to guide this decision We start with 24 mlkg (1 mlkgh) and then increase by this amount each day Most babies achieve full enteral feeds (ge150 mlkgd) by a week of age Feeding guidelines improve the outcome8 Measure-ment or assessment of gastric aspirates is not consistently useful in predicting subsequent feeding intolerance or development of NEC Aspirate volumes equivalent to or sometimes greater than the amount given in the preceding 1ndash2 h are usually normal Most aspirates have a greenish colour Thick bloody or intensely bile-stained aspirates require detailed assessment
0 copy 2008 elsevier ltd all rights reserved
Personal Practice
What else affects decisions and outcome
Feeding success is affected by sepsis and NEC Scrupulous atten-tion should be paid to hand washing and intravenous access and blood sampling should be minimized There is no good evidence to support the routine use of pro-kinetic agents or H2 blockers
The most important clinical intervention affecting the occur-rence of NEC is the use of breast milk9 All efforts should be directed at persuading parents of the benefits and supporting the process Some clinicians delay starting feeds for a further 24 h whilst expressed breast milk becomes available Donor breast milk might be equally efficacious10
RefeRenceS
1 Dorling J Kempley s leaf a Feeding growth restricted preterm
infants with abnormal antenatal Doppler results Arch Dis Child Fetal
Neonatal Ed 2005 90 F359ndash363
2 schmidt B roberts rs Davis P et al caffeine therapy for apnea of
prematurity N Engl J Med 2006 354 2112ndash2121
PaeDiatrics anD cHilD HealtH 184 20
3 embleton nD Pang n cooke rJ Postnatal malnutrition and growth
retardation an inevitable consequence of current recommendations
in preterm infants Pediatrics 2001 107 270ndash273
4 Berseth cl Bisquera Ja Paje VU Prolonging small feeding volumes
early in life decreases the incidence of necrotizing enterocolitis in
very low birth weight infants Pediatrics 2003 111 529ndash534
5 Menon G Boyle eM embleton nD et al introduction of enteral
feeds in preterm infants Pediatrics 2004 114 327ndash328
6 Kennedy Ka tyson Je chamnanvanikij s early versus delayed
initiation of progressive enteral feedings for parenterally fed low
birth weight or preterm infants Cochrane Database Syst Rev 2000
cD001970
7 wwwnpeuoxacukadept
8 Patole sK de Klerk n impact of standardised feeding regimens on
incidence of neonatal necrotising enterocolitis a systematic review
and meta-analysis of observational studies Arch Dis Child Fetal
Neonatal Ed 2005 90 F147ndash151
9 lucas a cole tJ Breast milk and neonatal necrotising enterocolitis
Lancet 1990 336 1519ndash1523
10 Boyd ca Quigley Ma Brocklehurst P Donor breast milk versus
infant formula for preterm infants systematic review and meta-
analysis Arch Dis Child Fetal Neonatal Ed 2007 92 F169ndash175
1 copy 2008 elsevier ltd all rights reserved
self-assessment
Case 1A term male infant born to consanguineous parents is assessed at 24 h of age due to poor feeding profuse yellow watery diar-rhoea and irritability He weighed 32 kg at birth and delivery was uneventful There was no polyhydramnios He has been breastfed since birth On examination he is pale with a non-tender but distended abdomen and reduced bowel sounds His weight is 275 kg and he looks dehydrated Examination is otherwise normal
Initial investigations (normal values in parentheses) showed
sodium 149 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 65 mmollitre (25ndash75)
creatinine 147 μmollitre (40ndash110)
chloride 119 mmollitre (95ndash105)
haemoglobin 172 gdl (140ndash200)
White blood cell count 80 times 109litre (100ndash260)
Platelet count 302 times 109litre (150ndash400)
arterial blood gas
ph 720 (730ndash745)
PcO2 23 kPa (46ndash60)
Bicarbonate 68 mmollitre (220ndash260)
Base excess minus186 mmollitre (minus20 to +20)
lactate 59 mmollitre (06ndash24)
An abdominal X-ray shows distended bowel loops with no intramural thickening or pneumoperitoneum (Figure 1)
He was given nil by mouth and received intravenous fluids and antibiotics His dehydration improved but the metabolic acidosis and diarrhoea persisted despite receiving no enteral feeds and the commencement of total parenteral nutrition Blood and stool cultures were negative
1 Which of the following best describes these results Choose ONE answer ONLY from the followingA Hypernatraemia hyperchloraemic metabolic acidosis
with increased anion gapB Hypernatraemia hyperchloraemic metabolic acidosis
with normal anion gap
Manish Sadarangani BM BCh MA MRCPCH is Clinical Research Fellow
at the Department of Paediatrics University of Oxford Centre for
Clinical Vaccinology and Tropical Medicine Churchill Hospital
Oxford OX3 7LJ UK
Shabna Rajapaksa MB BChir MA MRCPCH is Specialist Registrar in
Paediatrics at the Paediatric Intensive Care Unit John Radcliffe
Hospital Oxford OX3 9DU UK
Nicholas Mann MD FRCP FRCPCH DCH is Consultant Paediatrician at the
Department of Paediatrics Royal Berkshire Hospital Reading RG1
5AN UK
self-assessment
C Hypernatraemic dehydration and compensated metabolic acidosis
D Acute renal failureE Renal tubular acidosis
2 What is the likely diagnosis Choose ONE answer ONLY from the followingA Hirschsprung disease ndash long segmentB Cystic fibrosis with meconium ileusC Microvillus inclusion diseaseD Cowrsquos milk protein intoleranceE Lactose intolerance
3 What is the investigation of choice Choose ONE answer ONLY from the followingA Rectal biopsy with staining for acetylcholine receptorsB Immunoreactive trypsinC Gastrointestinal endoscopy and biopsyD Stool microscopy and cultureE Stool reducing substances
Case 2A 4-year-old boy presents with a 3 d history of jaundice and a florid rash He has had orange urine and there is no change in his stool colour His family originate from Kosovo and have lived in the UK for the last 8 years He has never left the UK There is no history of blood transfusion or sex-ual abuse The grandmother was recently diagnosed with hepatitis B
On examination he is well apyrexial and mildly jaundiced with cervical and axillary lymphadenopathy He has an exten-sive papular rash over the face extremities and trunk (Figure 2) There is 3 cm hepatomegaly with no splenomegaly or ascites Examination is otherwise normal
Figure 1 abdominal X-ray of baby
Paediatrics and child health 184 202 copy 2008 elsevier ltd all rights reserved
self-assessment
Initial investigations are as follows
haemoglobin 110 gdl (113ndash135)
White blood cell count 108 times 109litre (50ndash150)
Platelet count 278 times 109litre (150ndash400)
inr 10 (08ndash12)
aPt ratio 10 (08ndash13)
sodium 140 mmollitre (135ndash145)
Potassium 42 mmollitre (35ndash50)
Urea 56 mmollitre (25ndash75)
creatinine 65 μmollitre (45ndash120)
total bilirubin 66 μmollitre (0ndash15)
conjugated bilirubin 23 μmollitre (0ndash10)
alanine aminotransferase (alt) 2033 iUlitre (0ndash35)
alkaline phosphatase 987 iUlitre (71ndash234)
Gamma-glutamyl transferase (GGt) 870 iUlitre (0ndash51)
1 What is the name of this rash Choose ONE answer ONLY from the followingA Erythema multiformeB Erythema migransC GianottiminusCrosti syndromeD EczemaE Dermatitis herpetiformis
2 What is the most likely diagnosis Choose ONE Answer ONLY from the followingA Autoimmune hepatitisB Hepatitis BC Hepatitis DD Wilson diseaseE Alpha-1 antitrypsin deficiency
3 What is the best means of management Choose ONE answer ONLY from the followingA Isolation until the jaundice disappearsB ImmunosuppressionC Copper chelating agents and genetic counsellingD Patient and family education with consideration of
antiviral agentsE Liver transplantation
Case 3A 10-month-old boy presents with 3 weeks of vomiting and constipation ndash he is passing hard stools every 2ndash3 days He has fallen from the 9th to below the 04th centile in the last 6 weeks He passed meconium within the first 24 h of life On examina-tion he looks pale and there are some dysmorphic features ndash a short nose long philtrum and wide mouth He has normal heart sounds with a grade 3 ejection systolic murmur loudest at the upper right sternal edge Examination is otherwise normal
Initial investigations are as follows
haemoglobin 91 gdl (113ndash141)
total white blood cell count 124 times 109litre (60ndash170)
Platelet count 407 times 109litre (150ndash400)
sodium 144 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 78 mmollitre (25ndash75)
creatinine 78 μmollitre (45ndash120)
albumin 52 glitre (35ndash50)
corrected calcium 384 mmollitre (238ndash263)
Phosphate 167 mmollitre (099ndash157)
1 What is the most likely diagnosis Choose ONE answer ONLY from the followingA HyperparathyroidismB Acute leukaemiaC Williams syndromeD Hypervitaminosis DE Familial hypocalciuric hypercalcaemia
2 Which investigation would be most useful in establishing the diagnosis Choose ONE answer ONLY from the followingA Intact parathyroid hormone assayB Blood filmC Fluorescent in-situ hybridization for 7q1123 deletionD 25-hydroxyvitamin D assayE Urine calciumcreatinine ratio
3 Which of the following treatments would not be suitable for this patient Choose ONE answer ONLY from the followingA Low calcium dietB Normal saline infusionC FurosemideD CorticosteroidsE Bisphosphonates
Case 4A 10-week-old girl presents with a 2-day history of poor feed-ing Her mother has been concerned about weakness since birth She only has a flicker of movement in the arms none in the legs and has a weak cry She has been passing urine and opening her bowels normally She was born at full term by normal delivery and did not require any resuscitation at birth Normal fetal movements were felt antenatally and there was no polyhydramnios She is the first child of non- consanguineous parents and there is no significant family his-tory On examination she is alert and fixing and following appropriately She has a weak cry and a weak suck There is reduced central and peripheral tone with marked head lag
Figure 2 rash found on examination
Paediatrics and child health 184 203 copy 2008 elsevier ltd all rights reserved
self-assessment
Muscle power is grade 3 out of 5 in the arms and legs There is no muscle or tongue fasciculation and she has absent reflexes throughout The remainder of the examination is normal
Electromyogram shows irregular polyphasic motor unit potentials with marked instability consistent with a dener-vating and re-innervating process (Figure 3)
1 Which of the following additional investigations may be helpful Choose ONE answer ONLY from the followingA Nerve conduction studiesB Creatine kinase assayC Muscle biopsyD SMN1 gene analysisE All of the above
2 What is the most likely cause of this childrsquos symptoms Choose ONE answer ONLY from the followingA Congenital myotonic dystrophyB Duchenne muscular dystrophyC PraderminusWilli syndromeD Spinal muscular atrophyE Mitochondrial myopathy
3 What is the mode of inheritance of this disease Choose ONE answer ONLY from the followingA X-linked recessiveB Autosomal recessiveC Autosomal dominantD MitochondrialE Sporadic
Case 5A 13-year-old girl presents with a 3-week history of fever up to 40degC night sweats and headache She has a reduced appetite with some weight loss She has no other specific symptoms She was on holiday in China 7 months ago On examination she looks well and has a temperature of 387degC There is no lymphadenopathy and no rashes Examination is entirely normal
Results of investigations are as follows
haemoglobin 126 gdl (120ndash160)
total white blood cell count 132 times 109litre (43ndash108)
neutrophil count 115 times 109litre (25ndash75)
Platelet count 244 times 109litre (150ndash400)
Blood film neutrophilia with left shift
erythrocyte sedimentation rate 63 mmh (1ndash20)
c-reactive protein 219 mglitre (0ndash5)
Blood culture Streptococcus intermedius
from anaerobic bottle only
csf culture negative
Magnetic resonance imaging (MRI) of the brain shows acute frontal sinusitis with a large intracranial frontal extra-dural empyema (Figure 4)
1 Which of the following would be appropriate management Choose ONE answer ONLY from the followingA A 12-week course of intravenous antibioticsB Drainage of the frontal sinus followed by 2 weeks of
intravenous antibioticsC Drainage of the empyema followed by 2 weeks of
intravenous antibioticsD Drainage of the empyema and the frontal sinus
followed by 2 weeks of oral antibiotics
1151
1152
1153
1154
1155
1156
1157
1158
1159
1200
50ms 1mV
Figure 3 electromyogram recording from the patient Figure 4 Parasagittal section from mri scan of patient
Paediatrics and child health 184 204 copy 2008 elsevier ltd all rights reserved
self-assessment
E Drainage of the empyema and the frontal sinus followed by 8 weeks of intravenous antibiotics
2 Streptococcus intermedius is a potential pathogen in which of the following infections Choose ONE answer ONLY from the followingA Liver abscessB Urinary tract infectionC MeningitisD Thoracic empyemaE Pneumonia
3 Which of the following statements regarding lsquopyrexia of unknown originrsquo in children is false Choose ONE answer ONLY from the followingA Malignancy is the underlying pathology in 5ndash15 of
casesB An aetiology will be found in over 90 of casesC The most common cause is infectionD A rheumatological cause is found in 10ndash20 of casesE Familial Mediterranean fever can occur in children of
non-Mediterranean ethnicity
Answers
Case 11 AThe anion gap is a useful tool to differentiate the causes of a metabolic acidosis It is calculated by the equation
Anion gap = [Na K ] [Cl HCO ]3+ + minus minus+ minus +
It represents the effect of unmeasured anions on the plasma pH and is normally 10ndash18 mmollitre
2 CMicrovillus inclusion disease is a severe autosomal recessive enteropathy that is typically apparent within hours or days after birth It is the second most common cause of protracted diarrhoea in the newborn after infectious causes It is characterized by severe yellow watery diarrhoea and malabsorption due to hypoplasia andor atrophy of the villi of the small intestine secondary to an inherited defect in the brush border membrane This results in severe dehydration malnutrition and metabolic acidosis due to bicarbonate loss from the gut
3 CDiagnosis of microvillus inclusion disease is made on small bowel biopsy Electron microscopy findings are of intracellular brush border inclusions and densely packed apical cytoplasmic vesicular bodies indicating microvillous atrophy There is no cure Treatment is supportive with total parenteral nutrition and consideration of small bowel transplantation
Further reAding
Goulet O ruemmele f causes and management of intestinal failure
in children Gastroenterology 2006 130(suppl 1) s16ndash28
rhoads Jm Vogler rc lacey sr et al microvillus inclusion disease
In vitro jejunal electrolyte transport Gastroenterology 1991
100 811ndash817
Case 21 CGianottindashCrosti syndrome is a distinct self-limiting rash commonly associated with viral infections in children between 2 and 6 years of age It presents as multiple pink to redminusbrown papules or papulovesicles which may be pruritic and can become confluent Gianotti and Crosti initially described the exanthema as associated with hepatitis B virus and they termed it papular acrodermatitis of childhood It can occur in several viral diseases eg hepatitis A B and C coxsackie viruses and cytomegalovirus
2 BHepatitis is a syndrome characterized by inflammation or injury of liver cells which may develop into cell necrosis and subsequently fibrosis andor cirrhosis Biochemically there are raised liver enzymes The degree of transaminase elevation does not correlate with the severity of the disease process Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of viral hepatitis
3 DHepatitis B infection is transmitted via blood sexually or vertically Infection may be acute or chronic Diagnostic markers are the presence of surface antigen (HBsAg) and HBV DNA The presence of e antigen (HBeAg) indicates high infectivity Infected newborns have a 95 risk of becoming carriers this risk decreases with infection acquired later in childhood Approximately 15ndash25 of HBV carriers will die from cirrhosis or hepatocellular carcinoma Extrahepatic findings are more common in older children and include membranous glomerulonephritis and GianottiminusCrosti syndrome Fulminant hepatic failure occurs in severe cases resulting in persistent jaundice encephalopathy and coagulopathy Management includes counselling family members monitoring for ongoing liver disease and consideration of antiviral therapy
Further reAding
Brandt O abeck d Gianotti r Burgdorf W Gianotti crosti
syndrome J Am Acad Dermatol 2006 54 136ndash145
slowik mK Jhaveri r hepatitis B and c viruses in infants and
young children Semin Pediatr Infect Dis 2005 16 296ndash305
Case 31 CHypercalcaemia is uncommon in infancy The most common symptoms in this age group are irritability vomiting and constipation It may be a manifestation of Williams syndrome vitamin D or calcium excess as well as disorders associated with reduced bone formation such as hypophosphatasia or increased bone resorption such as malignancy Occasionally
Paediatrics and child health 184 205 copy 2008 elsevier ltd all rights reserved
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-
SympoSium neonatology
Recognition and management of neonatal seizuresmalcolm levene
AbstractSeizures are the most common major manifestation of central nervous
system dysfunction in the newborn there are many causes but perina-
tal asphyxia and haemorrhagicinfarction lesions account for about 75
there is now considerable evidence that frequent but short seizures in
the neonate affect subsequent neurodevelopmental outcome Studies
using eeg or modified continuous tracing of eeg activity (aeeg or CFm)
have shown that there is often electroconvulsive dissociation this re-
fers to poor correlation between electrical seizures and clinical seizures
Commonly used anticonvulsants appear to increase electroconvulsive
dissociation effective management of neonatal seizures has proved very
disappointing and less than 50 of seizures are abolished by first-line
anticonvulsant medication (phenobarbitone or phenytoin) Drugs such
as midazolam and lidocaine may further reduce seizures but require
more evaluation the challenge is to assess new and more effective anti-
convulsants which are themselves associated with little neurotoxicity
Keywords antiepileptic drugs eeg neonatal seizures neurodegeneration
Convulsions are the most common major neurological sign seen in newborn infants and their incidence estimated from large population studies is 26 per 1000 live births1 Premature infants are over four times more likely to have convulsions than full-term infants12 Neonatal status epilepticus (continuous seizure activity lasting 30 min or more) diagnosed clinically is rare and accounts for only 5 of infants with seizures1 although this is now recognized more frequently as the result of continuous EEG monitoring3
Neonatal convulsions are described as presenting in a num-ber of different ways and various seizure types can be seen in the same baby over a number of hours The frequencies of the various patterns of seizure activity are given in Table 1 In very premature babies and to a lesser extent in term infants minor movement abnormalities may be difficult to identify as subtle seizures These include lip smacking tongue thrusting mouth-ing pedalling type movements of the lower limbs or swimming movements of the arms Apnoea can be a common manifesta-tion of subtle seizures The signs can be protean and vary from baby to baby or even in the same baby Virtually any stereotypic
Malcolm Levene MD FMedSc FRCPCH FRCH is Professor and Head of
Department of Paediatrics and Child Health at University of Leeds Leeds
and Honorary Neonatologist at Leeds General Infirmary Leeds UK
paeDiatRiCS anD CHilD HealtH 184 178
movement may be a manifestation of a seizure disorder in the newborn
Aetiology
The more carefully the fitting baby is investigated the more likely it is that a cause for the seizures will be found A number of recent papers have described the aetiology of neonatal con-vulsions after extensive investigations14 Tekgul et al4 recently studied a consecutive group of full-term infants with evidence of neonatal convulsions (recognized both clinically and on EEG) and reported their outcome Table 2 summarizes these data as well as risk of moderate or severe disability for each causative factor Perinatal asphyxia is the commonest cause for convul-sions in term infants with haemorrhagic or ischaemic lesions also being common
Overall the prognosis for the group of term babies with con-vulsions was good 72 had a favourable outcome Where asphyxia (hypoxicndashischaemic insult) is the cause of neonatal convulsions the outcome is poor in 50 The prognosis for neonatal convulsions when they were due to arterial or cere-brovenous infarction or intracranial haemorrhage was generally good Individually inborn errors are a very rare cause of neo-natal convulsions but in view of the treatable nature of some of these it is essential that these be considered and investigated appropriately5
Patterns of seizure activity in the newborn
Movement pattern Frequency ()
Clonic 50
tonic 20
Subtle 10ndash35 depending on maturity
myoclonic 5
Table 1
Cause incidence and outcome of neonatal convulsions in term infants14
Aetiological factor Incidence () Poor outcome ()
asphyxia 38ndash40 50
Cerebral arteriovenous
infarction
20 0
intracranial haemorrhage 12ndash20 13
Congenital cerebral anomaly 5ndash10 100
Hypoglycaemiahypocalcaemia 3ndash19
infection 3ndash20
inborn error of metabolism 1
unknown cause 10ndash13 0
Refers to moderate and severe neurodevelopmental abnormalitynumbers too small to make meaningful predictions
Table 2
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Controversies in the clinical management of neonatal seizures
In recent years we have learnt much more about the neurobi-ology of seizures and their effect on the developing brain The neonatal brain is in a neurophysiologically hyperexcitable state compared to the more mature brain and therefore is more prone to seizure activity This is due largely to a relative excess of GABA neuroreceptors GABA receptors are usually inhibitory but in the immature brain they have a paradoxically excitatory effect This changes at about term in primates and with progressive develop-ment they adopt a neuroinhibitory role6
The propensity to seizures in the neonatal brain makes resolv-ing the balance of risks between continuing seizure activity on the one hand against potentially adverse effects of therapy on the other a very important equation Added to this is the problem of accurately diagnosing neonatal seizures and whether commonly used anticonvulsants are successful in controlling them
These conundrums can be posed as a series of challenging questions which are discussed below
Do neonatal convulsions cause brain injuryConvulsions are a sign of neurological compromise and may indi-cate significant underlying structural brain damage or biochemi-cal disturbance which may cause further brain damage in its own right There has been considerable debate about the scale of the disability that convulsions cause the immature brain over and above that due to the underlying cause Most of our knowledge comes from studies in rodents and these have provided some tentative answers to this question
Seizures in the mature brain lead to neuronal necrosis but studies in very young rat pups whose brain development is somewhat similar to full-term infants have shown that a series of five brief seizures on five successive days does not cause struc-tural neuronal damage but does produce morphological changes in hippocampal neurones and worryingly deficits in the rat learning and visual spatial memory function in adolescent and adult life7 A single prolonged neonatal convulsion in similarly immature rats does not produce any functional effects8 Others have shown that following priming of the neonatal rat brain by short seizures as described above a further insult comprising induction of status epilepticus in the same rats at an older age causes neuronal necrosis9 This has been referred to as the lsquotwo hit hypothesisrsquo10
A more specific question is does seizure activity in an already significantly compromised brain cause additional neuropathol-ogy Wirrell et al11 studied a series of immature rat pups with the induction of an hypoxicndashischaemic (asphyxial) insult fol-lowed by either chemically-induced fits or a control sham pro-cedure In the more severely asphyxiated animals the degree of brain damage was increased significantly in those that had the additional burden of induced seizures
In summary these studies show that the immature brain is more resistant to short frequent post-seizure damage than the mature brain but despite resulting in no loss of neuronal numbers the function of the brain is permanently affected in later life In the asphyxiated brain seizures appear to have an additional adverse effect on brain damage Furthermore the immature brain that has been lsquoprimedrsquo by early seizures is more
paeDiatRiCS anD CHilD HealtH 184 179
vulnerable to status epilepticus later in life It would appear from these data that frequent seizures in the human infant should be stopped and this begs the question as to whether currently used anticonvulsants effectively control neonatal seizures
Can we rely on clinical versus EEG diagnosis of neonatal convulsionsTraditionally the diagnosis of neonatal convulsions has been made by observation and description of the frequency of abnor-mal movements EEG has been technically difficult in the hostile electrical activity of a neonatal intensive care environment and considerable expertise is required for analysis of the trace It is usually not practical to undertake traditional EEG recordings at the time the baby shows abnormal movements More recently various technological developments have allowed more direct investigation of neuronal electrical activity by either video-EEG or compressed recording of the amplitude integrated EEG (aEEG or CFM)
Rennie et al3 at Kingrsquos College Hospital London have under-taken extensive evaluation of video-EEG and have found that this technique detects many convulsions not recognized by a single channel aEEG or CFM trace Of 19 infants with evidence of convulsions on EEG only four were recognized on CFM but this may have been due to the observersrsquo lack of experi-ence with this technique In other centres that have developed appropriate expertise aEEG or CFM has proved more sensitive to the detection of seizures Video-EEG studies have also shown that many movements interpreted by experienced clinicians to be seizures are not associated with abnormal cortical activity Conversely many electrical seizures are not associated with abnormal movements This is referred to as electroconvulsive dissociation
In summary clinical observation alone to detect the fitting baby is unreliable in that it may either over-detect seizure activ-ity which is not present on EEG or under-detect clinical seizures in infants with EEG-proven convulsions The decision as to which babies to treat with antiepileptic drugs therefore becomes somewhat arbitrary
Do anticonvulsants stop neonatal seizuresAlthough neonatal seizures are common there are few random-ized controlled trials assessing the benefits of antiepileptic drugs (AEDs) in the treatment of this condition Phenobarbitone is the most widely used first-line AED and in an Australasian study 95 of neonatologists and paediatric neurologists used this drug as first-line management12 The most commonly used loading dosage is 20 mgkg but regimens of up to 40 mgkg have been recommended (Table 3)13 Four trials have evaluated the effect of phenobarbitone in abolishing neonatal seizures Two of these studies used EEG to monitor response to the drug1415 and one compared phenobarbitone with phenytoin15 In the latter study seizures were completely controlled in only 43 of babies and in the group where phenytoin was the first drug used com-plete seizure control was achieved in 45 This study switched babies from their first AED to the other if complete control was not obtained on EEG monitoring after exposure to first-line therapy In babies who had been given phenobarbitone as first-line therapy seizure control was only achieved in 57 after phenytoin was added In those given phenytoin first complete
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Dosage regimens for first- second- and third-line anticonvulsants in the neonatal period
Loading dose Second loading dose if first
unsuccessfulMaintenance dose
phenobarbitone 20 mgkg by slow iv injection 10 mgkg iv 25ndash5 mgkg od
phenytoin 20 mgkg iv over 20 min not recommended
midazolam 150ndash200 μgkg iv infusion 1 μgkgmin iv infusion increasing to 5 μgkgmin
until favourable response
lidocaine 2 mgkg iv over 10 min 6 mgkgh for 6 h iv then 4 mgkgh for 12 h then
2 mgkgh for 12 h
lorazepam 005ndash01 mgkg by slow iv injection
Diazepam 03ndash04 mgkg iv over 3ndash5 min
lidocaine should not be used if the infant has previously been treated with phenytoin
Table 3
seizure control was achieved with the adding of phenobarbitone in 62
Boylan et al14 assessed the efficacy of phenobarbitone (20ndash40 mgkg iv over 20 min) in 14 babies monitored by video-EEG in only four was there complete abolition of seizures and in the other 10 electroconvulsive seizure activity increased whereas clinical evidence of seizures reduced This has been termed elec-troclinical dissociation and anticonvulsant drug use in the new-born appears to increase this feature They also showed that the babies least likely to respond to the first-line AED are those with the most abnormal background EEG
Two studies have evaluated the use of phenobarbitone in babies who had sustained significant asphyxial insult at birth Hall et al13 compared high-dose phenobarbitone (mean 39 mgkg) versus standard dose (27 mgkg) and reported fewer convul-sions and a significant reduction of severe disability or death in the high dose group (RR 030 CI 010ndash093) A recent study from India16 of babies with hypoxicndashischaemic encephalopathy ran-domized 25 babies to phenobarbitone (20 mgkg loading dose) and compared them with 20 control babies Only 2 of 25 (4) in the phenobarbitone group developed convulsions compared with 8 of 20 (40) in the control group (p = 001) Because of the specific enrolment criteria (asphyxial insult) neither of these studies is strictly comparable to the studies by Painter et al15 and Boylan et al14 whose intention was to assess the efficacy of first-line anticonvulsant therapy on convulsions of any cause diagnosed either clinically or by EEG
Other anticonvulsants used as second- and third-line drugs have been subject to few studies in the newborn Midazolam is administered as a bolus followed by continuous infusion A recent study17 has shown that in 10 of 13 neonates given intravenous midazolam for status epilepticus control of electri-cal seizures was achieved within the first hour of treatment having been previously shown to be refractory to phenobarbi-tone treatment Some of these babies required a second bolus infusion of midazolam to obtain control of all electrographic seizures
In some parts of Europe lidocaine is used as a third-line anti-convulsant Malingre et al18 evaluated 20 infants refractory to
paeDiatRiCS anD CHilD HealtH 184 180
both phenobarbitone and midazolam and who were then given lidocaine by continuous infusion Lidocaine was effective in abolishing electroconvulsive seizures diagnosed by aEEG in 76 of the treatment courses studied No babies developed cardiac arrhythmias a previously reported complication of lidocaine in older patients As a result of pharmacokinetic studies the dosage regimen has been modified (see Table 3)
In summary phenobarbitone is effective in seizure control in less than 50 of babies and even when combined with phe-nytoin the efficacy of these drugs together remains poor More worrying is the observation that phenobarbitone tends to reduce clinically evident seizures thereby giving the clinician a false sense of security whilst having little or no effect on the num-bers of electroconvulsive disorders This has been summarized appropriately as lsquoafter all these years we still love what doesnrsquot workrsquo19 Both midazolam and lidocaine infusions appear to be effective in abolishing severe seizures in some infants resistant to phenobarbitone Lidocaine should not be given to babies previ-ously exposed to phenytoin for fear of a synergistic adverse effect on cardiac rhythm
Do antiepileptic drugs cause brain damageA riskndashbenefit analysis is needed to evaluate the efficacy of anticonvulsants in stopping neonatal seizures which is poor with standard anticonvulsants as discussed above against the risk of administering the anticonvulsant drugs themselves Phenobarbitone has been reported to have adverse effects on the developing brain including inhibition of brain growth20 neuronal toxicity21 and adverse behavioural and cognitive effects into adult life when administered to young animals22 Phenytoin shows unpredictable plasma levels and potential cardiotoxicity
Recent studies have shown an effect of AED exposure on the developing brain by causing neurodegeneration23 Phenytoin administration to immature rat pups at doses which produce serum levels similar to those achieved in human neonates was associated with widespread neuronal death as a result of apop-tosis (programmed cell death) Phenobarbitone had a similar effect when a dosage regimen similar to 40 mgkg was used and
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
this effect was maximal in the more immature brain Diazepam and clonazepam also resulted in a similar effect Midazolam and lidocaine were not tested in this study The combination of phenobarbitone or phenytoin with diazepam had a particularly profound effect on neurodegeneration
In summary recent data suggest that the commonly used AEDs for neonatal convulsions may in themselves cause neuro-degeneration due to apoptosis with lasting effects on develop-ment Many babies with neonatal convulsions are treated with at least two AEDs and this may produce more severe adverse effects than the seizures themselves
Practical management of neonatal seizures
Assimilation of these data and formulation of a rational policy is difficult when faced with a fitting neonate on an intensive care unit and pressure on the medical staff to lsquodo somethingrsquo but it is important to accept that sometimes doing nothing is preferable to using potentially dangerous drugs in a situation which does not warrant such intervention Many babies who have normal interseizure neurological clinical findings and whose seizures are relatively brief and infrequent probably do not need anticon-vulsant medication A normal or near-normal background EEG trace should reassure the clinician that anticonvulsants can be withheld
Some causes of neonatal convulsions are treatable such as meningitis hypoglycaemia hypocalcaemia and inborn errors of metabolism and each baby should be rapidly and carefully investigated for cause of the convulsions
In some babies clinical assessment of seizures is difficult ie when the baby is very sick small or paralyzed Sometimes it may be difficult to assess the significance of certain movement pat-terns Under these circumstances an EEG may prove to be very helpful In many units EEG is not available out of hours and a simple aEEG or CFM is strongly advised Modern instruments are very simple to apply and prolonged or frequent seizures should be identified with only moderate training The printout can be faxed to a more senior doctor if there is doubt as to what is shown on the trace
The balance of knowledge now is that frequent seizures cause additional damage to the developing brain and that treatment to abolish the seizures is warranted Unfortunately there is little evidence that the majority of seizures can be effectively termi-nated by current standard therapy Furthermore it appears that the more abnormal the background EEG the more difficult it is to control the seizures Nevertheless a written protocol for the management of neonatal convulsions is required on each unit Phenobarbitone and phenytoin remain the mainstay of treat-ment although their effectiveness is disappointing There is little to suggest that midazolam is more effective than lidocaine as third-line therapy but lidocaine is precluded if phenytoin has been previously used
In view of the anxiety as to the neurodegenerative effects on the immature brain of most anticonvulsants used in the neonatal period (particularly when multiple drugs are used) it is prefer-able to use only one drug to maximum dosage before introduc-ing a second In addition the duration of anticonvulsants should be minimized and the drugs stopped at the earliest opportu-nity It is my practice to stop anticonvulsants prior to discharge
paeDiatRiCS anD CHilD HealtH 184 18
from hospital if the baby is neurologically normal on clinical examination
REFEREnCES
1 Ronen gm penney S andrews W the epidemiology of clinical
neonatal seizures in newfoundland a population-based study
J Pediatr 1999 134 71ndash75
2 lanska mJ lanska DJ Baumann RJ et al a population-based study
of neonatal seizures in Fayette County Kentucky Neurology 1995
45 724ndash732
3 Rennie Jm Chorley g Boylan gB et al non-expert use of the
cerebral function monitor for neonatal seizure detection Arch Dis
Child Fetal Neonatal Ed 2004 89 F37ndashF40
4 tekgul H gauvreau K Soul J et al the current etoliologic profile
and neurodevelopmental outcome of seizures in term newborn
infants Pediatrics 2006 117 1270ndash1280
5 Surtees R Wolf n treatable neonatal epilepsy Arch Dis Child 2007
92 659ndash661
6 Ben-ari y Holmes gl effects of seizures on developmental
processes in the immature brain Lancet Neurol 2006 5 1055ndash
1063
7 Holmes gl gairsa Jl Chevassus-au-louis n et al Consequences of
neonatal seizures in the rat morphological and behavioral effects
Ann Neurol 1998 44 845ndash857
8 Stafstrom Ce Chronopoulos a thurber S et al age-dependent
cognitive and behavioural deficits following kainic-acid inducing
seizures Epilepsia 1993 34 420ndash432
9 Schmid R tandon p Stafstrom Ce et al effects of neonatal seizures
on subsequent seizure-induced brain injury Neurology 1999 53
1754ndash1761
10 Hoffmann aF Zhao Q Holmes gl Cognitive impairment following
status epilepticus and recurrent seizures during early development
support for the ldquotwo-hit hypothesisrdquo Epilepsy Behav 2004 5
873ndash877
11 Wirrell eC armstrong ea osman lD et al prolonged seizures
exacerbate perinatal hypoxic-ischemic brain damage Pediatr Res
2001 50 445ndash454
12 Carmo KB Barr p Drug treatment of neonatal seizures by
neonatologists and paediatric neurologists J Paediatr Child Health
2005 41 313ndash316
13 Hall Rt Hall FK Daily DK High-dose phenobarbital therapy in term
newborn infants with severe perinatal asphyxia a randomized
prospective study with three-year follow-up J Pediatr 1998 132
345ndash348
14 Boylan gB Rennie Jm pressler Rm et al phenobarbitone neonatal
seizures and video-eeg Arch Dis Child Fetal Neonatal Ed 2002 86
F165ndash170
15 painter mJ Scher mS Stein aD et al phenobarbital compared with
phenytoin for the treatment of neonatal seizures N Engl J Med
1999 341 485ndash489
16 Singh D Kumar p narang a a randomized controlled trial of
phenobarbital in neonates with hypoxic ischemic encephalopathy
J Matern Fetal Neonatal Med 2005 18 391ndash395
17 Castro Conde JR Borges H Domenech martinez e et al midazolam
in neonatal seizures with no response to phenobarbital Neurology
2005 64 876ndash879
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
18 malingre mm Van Rooij lgm Rademaker Cma et al Development
of an optimal lidocaine infusion strategy for neonatal seizures Eur
J Pediatr 2006 165 598ndash604
19 Sankar R painter mJ neonatal seizures after all these years we still
love what doesnrsquot work Neurology 2005 64 776ndash777
20 Diaz J Schain J Bailey Bg phenobarbital-induced brain growth
retardation in artificially reared rat pups Biol Neonate 1977 32 77ndash82
21 mattson RH phenobarbital toxicity in levy RH Dreifuss Fe
mattson RH et al eds antiepipeptic Drugs 3rd edn new york
Raven 1985 p 341ndash355
22 mikati ma Holmes gl Chronopoulos a et al phenobarbital
modifies seizure-related brain injury in the developing brain Ann
Neurol 1994 36 425ndash453
23 Bittigau p Sifringer m genz K et al antiepileptic drugs and
apoptotic neurodegeneration in the developing brain Proc Natl
Acad Sci U S A 2002 99 15089ndash15094
paeDiatRiCS anD CHilD HealtH 184 182
Practice points
bull the clinician needs to be aware that almost any repetitive
stereotype movement pattern can be a manifestation of
neonatal seizures
bull eeg is important in defining neonatal seizures
bull Frequent short-lived seizures have been shown to cause long-
term neurodevelopmental problems
bull Conventional anticonvulsant medication is ineffective in
abolishing neonatal seizures in greater than 50 of cases
bull there is evidence that exposure of the neonatal brain to
multiple anticonvulsants causes neuronal death
bull Future research is needed to evaluate more effective
anticonvulsants for treating this condition
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
Emotional support for families of sick neonatesMarina nicolaou
cristine Glazebrook
AbstractParents of sick neonates experience high levels of stress anxiety and
depression Most interventions with families of sick infants have focused
on fostering the motherndashinfant relationship through the provision of
information about infant developmental needs or through increased
motherndashinfant contact Many of these studies have reported improved
maternal well-being though there are some concerns about the scope
and practicality of large-scale interventions The few studies to have
prioritized emotional support for parents of sick neonates have pro-
duced encouraging results even interventions requiring relatively few re-
sources such as telephone support parent-to-parent support and group
support have been associated with reduced psychological morbidity for
parents The needs of parents can change throughout their infantrsquos hos-
pitalization and not all want or benefit from the provision of additional
support Thus neonatal intensive care units should aim to provide a
varied flexible and sustainable programme of support options Further
research should focus on the needs of fathers
Keywords mental health neonatal intensive care parents
The admission of an infant to neonatal care is acknowledged to be a source of considerable distress for families This review aims to explore evidence for the psychological impact on families of having an infant in neonatal intensive care and to identify evi-dence for the effectiveness of interventions to promote parental well-being It will conclude with recommendations for strategies to support parents of vulnerable infants and suggestions for fur-ther research
Psychological impact of neonatal care for parents
The majority of research examining the effect on parents of having a sick neonate has focused on families of premature or low birthweight infants Such research has found that parents with a sick neonate exhibit high levels of stress compared to normative samples and to parents of healthy full-term infants1 Singer et al2 examined the stress experienced by mothers of high-risk very low birthweight (VLBW) low-risk VLBW and term
Marina Nicolaou MPhil is a Teaching Assistant at the School of
Community Health Sciences University of Nottingham Nottingham UK
Cristine Glazebrook PhD is a Professor of Health Psychology at the School
of Community Health Sciences University of Nottingham Nottingham UK
PaeDiaTrics anD cHilD HealTH 184 196
infants Several self-report measures were used including the Brief Symptom Inventory the Parenting Stress Index (PSI) the Impact on Family Scale and the Family Inventory of Life Events and Changes (FILE) Mothers of VLBW infants had more psycho-logical distress at 1 month compared to mothers of term infants Mothers of high-risk VLBW infants also reported high psycho-logical distress at 2 years and high levels of parenting stress at 3 years Mothers have also been found to have higher stress levels compared to fathers Shaw et al3 examined the prevalence of acute stress disorder (ASD) in 40 parents whose infants were in the neonatal intensive care unit (NICU) Nearly half of the moth-ers (44) met the criteria for ASD although none of the fathers did Furthermore the severity of the symptoms (measured by the number of concurrent symptoms) was greater for the moth-ers than for the fathers3 The reasons behind this difference have been widely speculated with some believing that it is due to the mothersrsquo greater psychological involvement with the infant as evidenced by their general greater vulnerability to postpartum psychological disorder It could also reflect gender differences in coping style
Having an infant who requires intensive medical care repre-sents a significant emotional burden for families Not only is there extreme anxiety surrounding the infantrsquos health and distress for the childrsquos suffering there is also the unfamiliar and intimidating environment of the NICU to adjust to Hopper in her review of the literature identified sources of stress for parents of sick neo-nates as falling into three areas4 Situational factors included the severity of the infantrsquos illness and how parents adapted to the life crisis of having a sick infant Personal factors involved parental emotions about their roles and the instrumental and informa-tional support which were available to them The third area was classified as environmental sources of stress and included the environment of the NICU and the relationship between parents and members of staff This relationship has been examined by several studies in the nursing literature nurses are seen as ide-ally placed to provide the necessary support and information to parents with sick neonates However whilst some studies have shown that supportive and helpful hospital staff can have a posi-tive effect on parents other studies have highlighted the prob-lems and difficulties which can manifest It has been shown that parents and nurses often have very different ideas about issues eg the necessary skills and competencies needed in an NICU or the characteristics that make a lsquogood motherrsquo
Research has shown that there may be a relationship between high levels of parental stress and an increased likelihood of depression5 Postpartum depression is a psychiatric illness which appears in 10ndash15 of postpartum women Its reported preva-lence rates however have ranged from less than 10 up to 306 depending on the instruments used the population exam-ined and the timing of the research Several factors have been found to be associated with postpartum depression including poor social support and infant-related stressors6 Evidence indi-cates that postnatal depression may be underreported and this is of concern since the mental and psychological health of the mother can affect her relationship with her infant and thus the infantrsquos cognitive and emotional development5 Depressed moth-ers appear to look touch and talk to their infants less frequently and also appear to show fewer positive and more negative faces7 The vocalizations of mothers suffering with depression have also
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
been found to be less effective at promoting cognitive growth and learning in infants8
If researchers are interested in finding ways of providing sup-port for families of sick neonates then they must listen to what such families perceive their needs to be in order to avoid increas-ing anxiety and distress Furthermore the provision of appropri-ate support be it emotional informational or social will enhance parental coping abilities increase self-esteem and reduce anxiety It should be noted though that the research conducted around these issues has often taken lsquosupport needsrsquo as being synony-mous with lsquoinformation needsrsquo Such studies have examined the type the amount and quality of information that parents receive and perceive themselves as needing but have not explored in equal depth the perceived emotional support needs of families who have a sick infant In addition the needs of parents may change throughout their infantrsquos illness Ward examined the per-ceived needs of 52 parents of infants in an NICU9 Parents rated the needs of their hospitalized infant as most important along with the need to be reassured Interestingly they ranked their support needs as least important This research was conducted during the first week of the infantsrsquo hospitalization however which would explain the preoccupation of the parents with the infantrsquos health These results demonstrate that if researchers want to find ways of providing emotional support to parents of sick neonates they must be prepared not only to listen to parents but also to be flexible enough to satisfy the parentsrsquo changing needs and expectations
Interventions aimed at supporting parents
Most interventions that been evaluated in controlled studies have focused on supporting the motherndashinfant relationship and provid-ing information on infant development Many of these interven-tions have included the aim of improving the parental emotional state and thus psychological outcomes such as stress or anxi-ety have been assessed However few studies appear to include fathers This means that strategies implemented to provide emo-tional support to families of sick neonates are often derived from interventions tailored for mothers even though fathers may have different emotional needs
A wide range of interventions with mothers and infants has been evaluated in the NICU Increasing motherndashinfant contact through kangaroo care has been found to reduce maternal anxiety1011 and educational programmes delivered to fami-lies in the NICU have also been associated with reduced emo-tional difficulties in parents12ndash14 Kaaresen and colleagues implemented an intervention which consisted of eight sessions before discharge and four home visits all by trained nurses The sample included 71 premature infants in the intervention group 69 premature infants in the control group and 74 infants in the full-term control group The randomized controlled trial found that the intervention reduced parenting stress in both mothers and fathers of premature infants compared to controls to a level equivalent to parents in the term control group13 At 6 months corrected age mothers of preterm infants who had not received the intervention had total PSI scores which were 17 points higher than the mothers of infants born at term (an effect size of 057) A similar study evaluated the efficacy of an educationalndashbehavioural programmendashCreating Opportunities for
PaeDiaTrics anD cHilD HealTH 184 19
Parent Empowerment (COPE) ndash through a randomized controlled trial with 260 families of premature infants14 COPE was a four-phase educationalndashbehavioural programme which began as early as 2ndash4 d after mothers had given birth and continued until 1 week after discharge from the NICU The programme consisted of audiotaped and written infant behaviour information along with photographs which focused on common behaviours and characteristics of premature infants It also included various par-ent activities in the form of a four-phase workbook which aimed to assist mothers in the implementation of the experimental infor-mation COPE was found significantly to reduce maternal stress in the NICU as well as maternal anxiety and depressive symptoms after hospitalization In contrast a cluster randomized trial of a parenting intervention delivered to mothers of very premature infants from soon after birth showed no benefits for parenting stress1 The authors hypothesized that the intervention had not been of sufficient intensity particularly in the weeks surrounding discharge Neonatal care presents a significant barrier to parent-ing in the early weeks following a very preterm birth and so inter-ventions which focus on the developmental needs of infants and the parentndashchild relationship should particularly aim to support parents as they take on the parenting role There was also concern that the intervention had failed to reach those most at risk
Since large-scale projects can be costly to implement and may often fail to reach the families in most need it may be wiser to focus on intervention programmes which are more practical and easier to implement within a neonatal care setting Research has shown that even interventions which are based on one-off meet-ings with parents of sick neonates can be effective Jotzo and Poets examined the effect of an intervention programme aimed at reducing the severity of traumatic responses as a result of giv-ing birth prematurely15 Their programme consisted of a one-off intervention meeting along with additional psychological help throughout the hospitalization of the infant The meeting cov-ered a variety of issues including a reconstruction of the events shortly before and after the infantrsquos birth relaxation techniques discussion of coping strategies available resources and social support and support during emotional outbursts The measures used included the Impact of Event Scale (IES) and the Peritrau-matic Dissociative Experience Questionnaire At discharge the mothers who received the intervention were found to have a significantly lower traumatic impact as a result of premature birth Furthermore fewer mothers in the intervention group showed symptoms of clinically significant psychological trauma at discharge compared to mothers in the control group (36 vs 76)15 The lsquoParents Circle Programrsquo is another intervention with a similar structure16 This consisted of a 90 min session for parents with the aim of enhancing the developing relationship between parents and infants and to offer parents support A total of 104 parents (59 mothers and 45 fathers) and 44 members of hospital staff were asked to evaluate the programme and their results were analysed using content analysis Families reported gaining perspective on their situation feeling supported becom-ing aware of cues and optimizing interactions and becoming aware of available resources Parents and staff alike felt that participating in the intervention helped parents overcome the difficulties associated with the early time of their infantrsquos hos-pitalization Additional studies have also found positive results with fairly minimal interventions including discussion groups
7 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
in the NICU music during kangaroo care and pairing mothers of sick neonates with trained mothers who had been through similar experiences
Parent support programmes
Parent support programmes (PSPs) which are based in NICUs can provide parents with the opportunity to talk to parents who have been in similar situations and also to discuss their emo-tions with professionals who can help them cope with their situa-tion111718 The parent-to-parent support programme for mothers of preterm infants evaluated by Preyde and Ardal included edu-cational parental support group meetings and individual par-ent-to-parent support (primarily telephone support)19 Measures used included the Parental Stressor Scale NICU the State and the Trait Anxiety Inventories and the Beck Depression Inven-tory After 4 months of participation mothers in the intervention group reported lower levels of stress state anxiety and depres-sion compared to control group mothers The authors speculated however that the participants who were able to meet face to face with other parents were those who benefited the most Hurst conducted a comprehensive survey of an NICU-based PSP This PSP was provided in a variety of formats including a weekly parent support group hospital visitation and 24-h telephone sup-port20 Of the 477 participants 303 families used the PSP dur-ing a 2-year evaluation period with 78 using only one form of support and 18 using two forms Of a sub-sample of 48 parents asked to complete an evaluation of the PSP 92 stated that they would recommend such a programme to other parents Furthermore the majority of parents felt that it made them feel supported and helped them deal with their emotions20 This is an indication that such programmes can be very successful in sup-porting parents throughout their infantrsquos hospitalization It also shows that it can be beneficial to give parents several options and formats when it comes to such support services It is impor-tant to consider though that both the Hurst and the Preyde and Ardal studies found that some participants did not find the sup-port programmes helpful even reporting that they had caused them increased stress and anxiety Therefore it should not be assumed that support programmes will suit every individual and will provide the required support for all parents1920 NICUs need to be flexible enough to provide parents with a range of forms of support to choose from
The increased understanding of the strains that parents of sick neonates have to deal with has also led to efforts to improve customary practices in NICUs Family-centred care focuses on infants and their needs and attempts to redefine the relationship between parents and caregivers These practices strive to provide parents with support during their infantrsquos illness by focusing on freely sharing information and on the collaboration between parents and hospital staff Family-centred care has been found to be associated with several beneficial outcomes including improved parental satisfaction increased parental comfort staff satisfaction and decreased parental stress18 Research is already examining these practices and questioning how these can be improved further Such research reflects the increasing effort focused on lsquohumanizingrsquo the environment in NICUs in order to make parents feel more comfortable about spending time with their infants
PaeDiaTrics anD cHilD HealTH 184 19
Conclusion
Surprisingly few interventions have prioritized the provision of emotional support for parents of sick neonates or accounted for the changing needs and wishes of parents over the course of their infantrsquos care Large-scale supportive education-based inter-ventions have been shown to be effective in reducing parental distress However the feasibility and sustainability of such pro-grammes should also be considered Programmes which require significant additional resources can be expensive and there are also issues of training and quality control Interventions which require significant input from parents may also place additional burdens on families making them potentially less accessible to those most at risk Arguably the aim should be to explore ways of providing acceptable and effective informational support which could be complemented by emotional support from health professionals and from other parents in the unit Increasingly studies are exploring the use of computers and multimedia as an engaging flexible and cost-effective method of targeting indi-vidual needs and providing support and information Such com-puter-based and interactive multimedia interventions have been found to be successful with a range of patient groups and could therefore be examined as a complementary method of providing informational support to families with sick neonates
REfEREnCEs
1 Glazebrook c Marlow n israel c et al randomised trial of a
parenting intervention during neonatal intensive care Arch Dis Child
Fetal Neonatal Ed 2007 92 F438ndash443
2 singer lT salvator a Guo s collin M lilien l Baley J Maternal
psychological distress and parenting stress after the birth of a very
low-birth-weight infant JAMA 1999 281 799ndash805
3 shaw rJ Deblois T ikuta l Ginzburg K Fleisher B Koopman c
acute stress disorder among parents of infants in the neonatal
intensive care nursery Psychosomatics 2006 47 206ndash212
4 Hopper a sources of stress for parents of a sick neonate a
literature review Pediatr Nurs 2000 30 29ndash32
5 Davis l edwards H Mohay H wollin J The impact of very
premature birth on the psychological health of mothers Early Hum
Dev 2003 73 61ndash70
6 Bernazzani O saucier J-F David H Borgeat F Psychosocial
predictors of depressive symptomatology level in postpartum
women J Affect Disord 1997 46 39ndash49
7 Field T infants of depressed mothers Infant Behav Dev 1995 18
1ndash13
8 Kaplan Ps Bachorowski J-a Zarlengo-strouse P child-directed
speech produced by mothers with symptoms of depression fails
to promote associative learning in 4-month-old infants Child Dev
1999 70 560ndash570
9 ward K Perceived needs of parents of critically ill infants in
a neonatal intensive care unit (nicU) Pediatr Nurs 2001 27
281ndash286
10 lai Hl chen cJ Peng Tc et al randomized controlled trial of music
during kangaroo care on maternal state anxiety and preterm infantsrsquo
responses Int J Nurs Stud 2006 43 139ndash146
8 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
11 Tallandini Ma scalembra c Kangaroo mother care and mother-
premature infant dyadic interaction Infant Ment Health J 2006 27
251ndash275
12 Ohgi s Fukuda M akiyama T Gima H effect of an early intervention
programme on low birthweight infants with cerebral injuries
J Paediatr Child Health 2004 40 689ndash695
13 Kaaresen Pi ronning Ja Ulvund se Dahl lB a randomized
controlled trial of the effectiveness of an early-intervention program
in reducing parenting stress after preterm birth Pediatrics 2006
118 e9ndash19
14 Melnyk BM Feinstein nF alpert-Gillis l et al reducing premature
infantsrsquo length of stay and improving parentsrsquo mental health
outcomes with the creating opportunities for parent empowerment
(cOPe) neonatal intensive care unit program a randomized
controlled trial Pediatrics 2006 118 e1414ndash1427
15 Jotzo M Poets cF Helping parents cope with the trauma of
premature birth an evaluation of a trauma-preventive psychological
intervention Pediatrics 2005 115 915ndash919
16 Pearson J andersen K evaluation of a program to promote positive
parenting in the neonatal intensive care unit Neonatal Netw 2001
20 43ndash48
17 roman l lindsay J Boger r et al Parent-to-parent support
initiated in the neonatal intensive care unit Res Nurs Health 1995
18 385ndash394
18 Meyer ec coll cTG lester BM Boukydis cFZ McDonough sM Oh w
Family-based intervention improves maternal psychological well-
being and feeding interaction of preterm infants Pediatrics 1994
93 241ndash246
PaeDiaTrics anD cHilD HealTH 184 19
19 Preyde M ardal F effectiveness of a parent ldquobuddyrdquo program for
mothers of very preterm infants in a neonatal intensive care unit
CMAJ 2003 168 969ndash973
20 Hurst i One size does not fit all Parentsrsquo evaluations of a support
program in a newborn intensive care nursery J Perinat Neonatal
Nurs 2006 20 252ndash261
Practice points
bull Parents of sick neonates experience significant distress and
exhibit higher levels of stress anxiety and depression than
parents of healthy infants
bull educational support emotional support and increased
motherndashinfant contact have been shown to promote maternal
well-being
bull emotional support for fathers has been largely neglected in
the research literature
bull Parents benefit from a choice of supportive facilities which
could include face-to-face sessions with health professionals
telephone support hospital visitation parent-to-parent
support and unit-based group support meetings
bull Parentsrsquo support needs can change during their infantrsquos
hospitalization and not all parents want or benefit from the
provision of additional information and emotional support in
the neonatal unit
9 copy 2008 elsevier ltd all rights reserved
Personal Practice
When should enteral feeds be started in preterm infantsnicholas D embleton
AbstractPaediatricians are regularly faced with the question of when best to start
enteral feeds in preterm infants this is important as longer term out-
come may be compromised by sub-optimal nutrition in early life clinical
factors that may affect the decision to start and the risk and benefits
are discussed
Keywords breast milk feeding nutrition parenteral nutrition
Key points in the history
Alice is lsquonutritionally vulnerablersquo and whilst this may not be immediately apparent it will affect her long term outcome Her energy stores are extremely limited and consist primarily of pro-tein She has less than 5 fat and little energy associated with stored glycogen She is losing about 1 gkgd protein equivalent so she needs at least that and a minimum of 50ndash60 kcalkg of energy just to maintain the status quo let alone grow
Her weight is on the 25th centile Review of any antenatal his-tory may reveal whether fetal growth was normal Fetal growth retardation can occur with a weight greater than 10th centile The presence of antenatal absent or reversed end diastolic flow in the umbilical artery indicates poor gut blood flow This increases the risk of necrotizing enterocolitis (NEC) and might suggest a more cautious approach to starting feeds1
She has no important cardiovascular problems but if she were hypotensive gut blood flow may be low There is no umbilical
Nicholas D Embleton BSC (Hons) MBBS (Hons) MD FRCPCH is Consultant in
Neonatal Medicine at Newcastle Neonatal Service Royal Victoria
Infirmary Newcastle upon Tyne NE1 4LP UK
Should you start feeds at a day of age
alice was born following spontaneous labour at 30 weeksrsquo
gestation she weighed 1300 g and is now 18 h old she was
briefly ventilated and then extubated to continuous positive
airway pressure 12 h ago in 35 oxygen she has had caffeine
citrate but still has intermittent episodes of self-correcting
apnoea she was commenced on iv 10 dextrose but this was
replaced by a parenteral amino acid solution (referred to as
lsquotPnrsquo) along with intralipid at 0900 this morning serum glucose
is 11 mmoll and blood pressure is 42 systolic
PaeDiatrics anD cHilD HealtH 184 20
arterial catheter in situ but there is no good evidence that this should delay the decision to start feeds Her glucose is high but this is quite common in a baby like this Could this be a sign of sepsis Caffeine does not affect the incidence of NEC2 The great-est risk factor for NEC in this case is prematurity
What else might be found on examination
Up until 24 h ago she was swallowing large amounts of amniotic fluid What will have changed since then
General examination should confirm peripheral perfusion lsquogestaltrsquo view (does she look lsquowellrsquo) and cardiovascular status lsquoBowel soundsrsquo are not usually helpful
The most important variable likely to affect gut perfusion is the arterial duct Precordial lsquoheaversquo and a loud murmur are sug-gestive but it is possible to have a significant ductal shunt in a baby with a normal examination Cardiac ultrasound will con-firm this diagnosis It might be better to treat a large shunt first with indometacin and to delay starting feeds for a further 24 h
It is not possible to assess gut perfusion clinically but normal perfusion elsewhere (adequate urine output usually indicates adequate renal perfusion) would be reassuring Most preterm babies have a few abdominal lsquoloopsrsquo visible but a distended abdomen with many palpable loops suggests ileus This might be secondary to sepsis or poor gut blood flow Preterm babies do not pass much meconium in the first 24ndash48 h
Balance of risks between starting and withholding feeds
Alice requires 35ndash4 gkgd of protein and 120 kcalkgd to grow3 This will initially be provided parenterally Delaying feeds increases the risk of gut villous atrophy and prolongs the need for lsquototal parenteral nutrition (TPN)rsquo TPN requires intravenous access and so increases the risk of sepsis and when prolonged use is required combined with the lack of enteral feeding may result in hepatic impairment
Delaying feeds may allow a gut that has been chronically under-perfused to re-establish more normal perfusion although normal gut endocrine function digestive enzyme upregulation and motility require a source of intraluminal nutrients1 A recent study suggested benefit from delaying the introduction of feeds4 but methodologi-cal problems exist5 Although a Cochrane meta-analysis suggested no benefit only two studies were included6 A large UK-based trial is examining the effect of early or late feeding in preterm infants who were born growth retarded following identification of antena-tal absent or reversed end diastolic flow in the umbilical artery7
When starting feeds what volume should be used
There are no good data to guide this decision We start with 24 mlkg (1 mlkgh) and then increase by this amount each day Most babies achieve full enteral feeds (ge150 mlkgd) by a week of age Feeding guidelines improve the outcome8 Measure-ment or assessment of gastric aspirates is not consistently useful in predicting subsequent feeding intolerance or development of NEC Aspirate volumes equivalent to or sometimes greater than the amount given in the preceding 1ndash2 h are usually normal Most aspirates have a greenish colour Thick bloody or intensely bile-stained aspirates require detailed assessment
0 copy 2008 elsevier ltd all rights reserved
Personal Practice
What else affects decisions and outcome
Feeding success is affected by sepsis and NEC Scrupulous atten-tion should be paid to hand washing and intravenous access and blood sampling should be minimized There is no good evidence to support the routine use of pro-kinetic agents or H2 blockers
The most important clinical intervention affecting the occur-rence of NEC is the use of breast milk9 All efforts should be directed at persuading parents of the benefits and supporting the process Some clinicians delay starting feeds for a further 24 h whilst expressed breast milk becomes available Donor breast milk might be equally efficacious10
RefeRenceS
1 Dorling J Kempley s leaf a Feeding growth restricted preterm
infants with abnormal antenatal Doppler results Arch Dis Child Fetal
Neonatal Ed 2005 90 F359ndash363
2 schmidt B roberts rs Davis P et al caffeine therapy for apnea of
prematurity N Engl J Med 2006 354 2112ndash2121
PaeDiatrics anD cHilD HealtH 184 20
3 embleton nD Pang n cooke rJ Postnatal malnutrition and growth
retardation an inevitable consequence of current recommendations
in preterm infants Pediatrics 2001 107 270ndash273
4 Berseth cl Bisquera Ja Paje VU Prolonging small feeding volumes
early in life decreases the incidence of necrotizing enterocolitis in
very low birth weight infants Pediatrics 2003 111 529ndash534
5 Menon G Boyle eM embleton nD et al introduction of enteral
feeds in preterm infants Pediatrics 2004 114 327ndash328
6 Kennedy Ka tyson Je chamnanvanikij s early versus delayed
initiation of progressive enteral feedings for parenterally fed low
birth weight or preterm infants Cochrane Database Syst Rev 2000
cD001970
7 wwwnpeuoxacukadept
8 Patole sK de Klerk n impact of standardised feeding regimens on
incidence of neonatal necrotising enterocolitis a systematic review
and meta-analysis of observational studies Arch Dis Child Fetal
Neonatal Ed 2005 90 F147ndash151
9 lucas a cole tJ Breast milk and neonatal necrotising enterocolitis
Lancet 1990 336 1519ndash1523
10 Boyd ca Quigley Ma Brocklehurst P Donor breast milk versus
infant formula for preterm infants systematic review and meta-
analysis Arch Dis Child Fetal Neonatal Ed 2007 92 F169ndash175
1 copy 2008 elsevier ltd all rights reserved
self-assessment
Case 1A term male infant born to consanguineous parents is assessed at 24 h of age due to poor feeding profuse yellow watery diar-rhoea and irritability He weighed 32 kg at birth and delivery was uneventful There was no polyhydramnios He has been breastfed since birth On examination he is pale with a non-tender but distended abdomen and reduced bowel sounds His weight is 275 kg and he looks dehydrated Examination is otherwise normal
Initial investigations (normal values in parentheses) showed
sodium 149 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 65 mmollitre (25ndash75)
creatinine 147 μmollitre (40ndash110)
chloride 119 mmollitre (95ndash105)
haemoglobin 172 gdl (140ndash200)
White blood cell count 80 times 109litre (100ndash260)
Platelet count 302 times 109litre (150ndash400)
arterial blood gas
ph 720 (730ndash745)
PcO2 23 kPa (46ndash60)
Bicarbonate 68 mmollitre (220ndash260)
Base excess minus186 mmollitre (minus20 to +20)
lactate 59 mmollitre (06ndash24)
An abdominal X-ray shows distended bowel loops with no intramural thickening or pneumoperitoneum (Figure 1)
He was given nil by mouth and received intravenous fluids and antibiotics His dehydration improved but the metabolic acidosis and diarrhoea persisted despite receiving no enteral feeds and the commencement of total parenteral nutrition Blood and stool cultures were negative
1 Which of the following best describes these results Choose ONE answer ONLY from the followingA Hypernatraemia hyperchloraemic metabolic acidosis
with increased anion gapB Hypernatraemia hyperchloraemic metabolic acidosis
with normal anion gap
Manish Sadarangani BM BCh MA MRCPCH is Clinical Research Fellow
at the Department of Paediatrics University of Oxford Centre for
Clinical Vaccinology and Tropical Medicine Churchill Hospital
Oxford OX3 7LJ UK
Shabna Rajapaksa MB BChir MA MRCPCH is Specialist Registrar in
Paediatrics at the Paediatric Intensive Care Unit John Radcliffe
Hospital Oxford OX3 9DU UK
Nicholas Mann MD FRCP FRCPCH DCH is Consultant Paediatrician at the
Department of Paediatrics Royal Berkshire Hospital Reading RG1
5AN UK
self-assessment
C Hypernatraemic dehydration and compensated metabolic acidosis
D Acute renal failureE Renal tubular acidosis
2 What is the likely diagnosis Choose ONE answer ONLY from the followingA Hirschsprung disease ndash long segmentB Cystic fibrosis with meconium ileusC Microvillus inclusion diseaseD Cowrsquos milk protein intoleranceE Lactose intolerance
3 What is the investigation of choice Choose ONE answer ONLY from the followingA Rectal biopsy with staining for acetylcholine receptorsB Immunoreactive trypsinC Gastrointestinal endoscopy and biopsyD Stool microscopy and cultureE Stool reducing substances
Case 2A 4-year-old boy presents with a 3 d history of jaundice and a florid rash He has had orange urine and there is no change in his stool colour His family originate from Kosovo and have lived in the UK for the last 8 years He has never left the UK There is no history of blood transfusion or sex-ual abuse The grandmother was recently diagnosed with hepatitis B
On examination he is well apyrexial and mildly jaundiced with cervical and axillary lymphadenopathy He has an exten-sive papular rash over the face extremities and trunk (Figure 2) There is 3 cm hepatomegaly with no splenomegaly or ascites Examination is otherwise normal
Figure 1 abdominal X-ray of baby
Paediatrics and child health 184 202 copy 2008 elsevier ltd all rights reserved
self-assessment
Initial investigations are as follows
haemoglobin 110 gdl (113ndash135)
White blood cell count 108 times 109litre (50ndash150)
Platelet count 278 times 109litre (150ndash400)
inr 10 (08ndash12)
aPt ratio 10 (08ndash13)
sodium 140 mmollitre (135ndash145)
Potassium 42 mmollitre (35ndash50)
Urea 56 mmollitre (25ndash75)
creatinine 65 μmollitre (45ndash120)
total bilirubin 66 μmollitre (0ndash15)
conjugated bilirubin 23 μmollitre (0ndash10)
alanine aminotransferase (alt) 2033 iUlitre (0ndash35)
alkaline phosphatase 987 iUlitre (71ndash234)
Gamma-glutamyl transferase (GGt) 870 iUlitre (0ndash51)
1 What is the name of this rash Choose ONE answer ONLY from the followingA Erythema multiformeB Erythema migransC GianottiminusCrosti syndromeD EczemaE Dermatitis herpetiformis
2 What is the most likely diagnosis Choose ONE Answer ONLY from the followingA Autoimmune hepatitisB Hepatitis BC Hepatitis DD Wilson diseaseE Alpha-1 antitrypsin deficiency
3 What is the best means of management Choose ONE answer ONLY from the followingA Isolation until the jaundice disappearsB ImmunosuppressionC Copper chelating agents and genetic counsellingD Patient and family education with consideration of
antiviral agentsE Liver transplantation
Case 3A 10-month-old boy presents with 3 weeks of vomiting and constipation ndash he is passing hard stools every 2ndash3 days He has fallen from the 9th to below the 04th centile in the last 6 weeks He passed meconium within the first 24 h of life On examina-tion he looks pale and there are some dysmorphic features ndash a short nose long philtrum and wide mouth He has normal heart sounds with a grade 3 ejection systolic murmur loudest at the upper right sternal edge Examination is otherwise normal
Initial investigations are as follows
haemoglobin 91 gdl (113ndash141)
total white blood cell count 124 times 109litre (60ndash170)
Platelet count 407 times 109litre (150ndash400)
sodium 144 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 78 mmollitre (25ndash75)
creatinine 78 μmollitre (45ndash120)
albumin 52 glitre (35ndash50)
corrected calcium 384 mmollitre (238ndash263)
Phosphate 167 mmollitre (099ndash157)
1 What is the most likely diagnosis Choose ONE answer ONLY from the followingA HyperparathyroidismB Acute leukaemiaC Williams syndromeD Hypervitaminosis DE Familial hypocalciuric hypercalcaemia
2 Which investigation would be most useful in establishing the diagnosis Choose ONE answer ONLY from the followingA Intact parathyroid hormone assayB Blood filmC Fluorescent in-situ hybridization for 7q1123 deletionD 25-hydroxyvitamin D assayE Urine calciumcreatinine ratio
3 Which of the following treatments would not be suitable for this patient Choose ONE answer ONLY from the followingA Low calcium dietB Normal saline infusionC FurosemideD CorticosteroidsE Bisphosphonates
Case 4A 10-week-old girl presents with a 2-day history of poor feed-ing Her mother has been concerned about weakness since birth She only has a flicker of movement in the arms none in the legs and has a weak cry She has been passing urine and opening her bowels normally She was born at full term by normal delivery and did not require any resuscitation at birth Normal fetal movements were felt antenatally and there was no polyhydramnios She is the first child of non- consanguineous parents and there is no significant family his-tory On examination she is alert and fixing and following appropriately She has a weak cry and a weak suck There is reduced central and peripheral tone with marked head lag
Figure 2 rash found on examination
Paediatrics and child health 184 203 copy 2008 elsevier ltd all rights reserved
self-assessment
Muscle power is grade 3 out of 5 in the arms and legs There is no muscle or tongue fasciculation and she has absent reflexes throughout The remainder of the examination is normal
Electromyogram shows irregular polyphasic motor unit potentials with marked instability consistent with a dener-vating and re-innervating process (Figure 3)
1 Which of the following additional investigations may be helpful Choose ONE answer ONLY from the followingA Nerve conduction studiesB Creatine kinase assayC Muscle biopsyD SMN1 gene analysisE All of the above
2 What is the most likely cause of this childrsquos symptoms Choose ONE answer ONLY from the followingA Congenital myotonic dystrophyB Duchenne muscular dystrophyC PraderminusWilli syndromeD Spinal muscular atrophyE Mitochondrial myopathy
3 What is the mode of inheritance of this disease Choose ONE answer ONLY from the followingA X-linked recessiveB Autosomal recessiveC Autosomal dominantD MitochondrialE Sporadic
Case 5A 13-year-old girl presents with a 3-week history of fever up to 40degC night sweats and headache She has a reduced appetite with some weight loss She has no other specific symptoms She was on holiday in China 7 months ago On examination she looks well and has a temperature of 387degC There is no lymphadenopathy and no rashes Examination is entirely normal
Results of investigations are as follows
haemoglobin 126 gdl (120ndash160)
total white blood cell count 132 times 109litre (43ndash108)
neutrophil count 115 times 109litre (25ndash75)
Platelet count 244 times 109litre (150ndash400)
Blood film neutrophilia with left shift
erythrocyte sedimentation rate 63 mmh (1ndash20)
c-reactive protein 219 mglitre (0ndash5)
Blood culture Streptococcus intermedius
from anaerobic bottle only
csf culture negative
Magnetic resonance imaging (MRI) of the brain shows acute frontal sinusitis with a large intracranial frontal extra-dural empyema (Figure 4)
1 Which of the following would be appropriate management Choose ONE answer ONLY from the followingA A 12-week course of intravenous antibioticsB Drainage of the frontal sinus followed by 2 weeks of
intravenous antibioticsC Drainage of the empyema followed by 2 weeks of
intravenous antibioticsD Drainage of the empyema and the frontal sinus
followed by 2 weeks of oral antibiotics
1151
1152
1153
1154
1155
1156
1157
1158
1159
1200
50ms 1mV
Figure 3 electromyogram recording from the patient Figure 4 Parasagittal section from mri scan of patient
Paediatrics and child health 184 204 copy 2008 elsevier ltd all rights reserved
self-assessment
E Drainage of the empyema and the frontal sinus followed by 8 weeks of intravenous antibiotics
2 Streptococcus intermedius is a potential pathogen in which of the following infections Choose ONE answer ONLY from the followingA Liver abscessB Urinary tract infectionC MeningitisD Thoracic empyemaE Pneumonia
3 Which of the following statements regarding lsquopyrexia of unknown originrsquo in children is false Choose ONE answer ONLY from the followingA Malignancy is the underlying pathology in 5ndash15 of
casesB An aetiology will be found in over 90 of casesC The most common cause is infectionD A rheumatological cause is found in 10ndash20 of casesE Familial Mediterranean fever can occur in children of
non-Mediterranean ethnicity
Answers
Case 11 AThe anion gap is a useful tool to differentiate the causes of a metabolic acidosis It is calculated by the equation
Anion gap = [Na K ] [Cl HCO ]3+ + minus minus+ minus +
It represents the effect of unmeasured anions on the plasma pH and is normally 10ndash18 mmollitre
2 CMicrovillus inclusion disease is a severe autosomal recessive enteropathy that is typically apparent within hours or days after birth It is the second most common cause of protracted diarrhoea in the newborn after infectious causes It is characterized by severe yellow watery diarrhoea and malabsorption due to hypoplasia andor atrophy of the villi of the small intestine secondary to an inherited defect in the brush border membrane This results in severe dehydration malnutrition and metabolic acidosis due to bicarbonate loss from the gut
3 CDiagnosis of microvillus inclusion disease is made on small bowel biopsy Electron microscopy findings are of intracellular brush border inclusions and densely packed apical cytoplasmic vesicular bodies indicating microvillous atrophy There is no cure Treatment is supportive with total parenteral nutrition and consideration of small bowel transplantation
Further reAding
Goulet O ruemmele f causes and management of intestinal failure
in children Gastroenterology 2006 130(suppl 1) s16ndash28
rhoads Jm Vogler rc lacey sr et al microvillus inclusion disease
In vitro jejunal electrolyte transport Gastroenterology 1991
100 811ndash817
Case 21 CGianottindashCrosti syndrome is a distinct self-limiting rash commonly associated with viral infections in children between 2 and 6 years of age It presents as multiple pink to redminusbrown papules or papulovesicles which may be pruritic and can become confluent Gianotti and Crosti initially described the exanthema as associated with hepatitis B virus and they termed it papular acrodermatitis of childhood It can occur in several viral diseases eg hepatitis A B and C coxsackie viruses and cytomegalovirus
2 BHepatitis is a syndrome characterized by inflammation or injury of liver cells which may develop into cell necrosis and subsequently fibrosis andor cirrhosis Biochemically there are raised liver enzymes The degree of transaminase elevation does not correlate with the severity of the disease process Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of viral hepatitis
3 DHepatitis B infection is transmitted via blood sexually or vertically Infection may be acute or chronic Diagnostic markers are the presence of surface antigen (HBsAg) and HBV DNA The presence of e antigen (HBeAg) indicates high infectivity Infected newborns have a 95 risk of becoming carriers this risk decreases with infection acquired later in childhood Approximately 15ndash25 of HBV carriers will die from cirrhosis or hepatocellular carcinoma Extrahepatic findings are more common in older children and include membranous glomerulonephritis and GianottiminusCrosti syndrome Fulminant hepatic failure occurs in severe cases resulting in persistent jaundice encephalopathy and coagulopathy Management includes counselling family members monitoring for ongoing liver disease and consideration of antiviral therapy
Further reAding
Brandt O abeck d Gianotti r Burgdorf W Gianotti crosti
syndrome J Am Acad Dermatol 2006 54 136ndash145
slowik mK Jhaveri r hepatitis B and c viruses in infants and
young children Semin Pediatr Infect Dis 2005 16 296ndash305
Case 31 CHypercalcaemia is uncommon in infancy The most common symptoms in this age group are irritability vomiting and constipation It may be a manifestation of Williams syndrome vitamin D or calcium excess as well as disorders associated with reduced bone formation such as hypophosphatasia or increased bone resorption such as malignancy Occasionally
Paediatrics and child health 184 205 copy 2008 elsevier ltd all rights reserved
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-
SympoSium neonatology
Controversies in the clinical management of neonatal seizures
In recent years we have learnt much more about the neurobi-ology of seizures and their effect on the developing brain The neonatal brain is in a neurophysiologically hyperexcitable state compared to the more mature brain and therefore is more prone to seizure activity This is due largely to a relative excess of GABA neuroreceptors GABA receptors are usually inhibitory but in the immature brain they have a paradoxically excitatory effect This changes at about term in primates and with progressive develop-ment they adopt a neuroinhibitory role6
The propensity to seizures in the neonatal brain makes resolv-ing the balance of risks between continuing seizure activity on the one hand against potentially adverse effects of therapy on the other a very important equation Added to this is the problem of accurately diagnosing neonatal seizures and whether commonly used anticonvulsants are successful in controlling them
These conundrums can be posed as a series of challenging questions which are discussed below
Do neonatal convulsions cause brain injuryConvulsions are a sign of neurological compromise and may indi-cate significant underlying structural brain damage or biochemi-cal disturbance which may cause further brain damage in its own right There has been considerable debate about the scale of the disability that convulsions cause the immature brain over and above that due to the underlying cause Most of our knowledge comes from studies in rodents and these have provided some tentative answers to this question
Seizures in the mature brain lead to neuronal necrosis but studies in very young rat pups whose brain development is somewhat similar to full-term infants have shown that a series of five brief seizures on five successive days does not cause struc-tural neuronal damage but does produce morphological changes in hippocampal neurones and worryingly deficits in the rat learning and visual spatial memory function in adolescent and adult life7 A single prolonged neonatal convulsion in similarly immature rats does not produce any functional effects8 Others have shown that following priming of the neonatal rat brain by short seizures as described above a further insult comprising induction of status epilepticus in the same rats at an older age causes neuronal necrosis9 This has been referred to as the lsquotwo hit hypothesisrsquo10
A more specific question is does seizure activity in an already significantly compromised brain cause additional neuropathol-ogy Wirrell et al11 studied a series of immature rat pups with the induction of an hypoxicndashischaemic (asphyxial) insult fol-lowed by either chemically-induced fits or a control sham pro-cedure In the more severely asphyxiated animals the degree of brain damage was increased significantly in those that had the additional burden of induced seizures
In summary these studies show that the immature brain is more resistant to short frequent post-seizure damage than the mature brain but despite resulting in no loss of neuronal numbers the function of the brain is permanently affected in later life In the asphyxiated brain seizures appear to have an additional adverse effect on brain damage Furthermore the immature brain that has been lsquoprimedrsquo by early seizures is more
paeDiatRiCS anD CHilD HealtH 184 179
vulnerable to status epilepticus later in life It would appear from these data that frequent seizures in the human infant should be stopped and this begs the question as to whether currently used anticonvulsants effectively control neonatal seizures
Can we rely on clinical versus EEG diagnosis of neonatal convulsionsTraditionally the diagnosis of neonatal convulsions has been made by observation and description of the frequency of abnor-mal movements EEG has been technically difficult in the hostile electrical activity of a neonatal intensive care environment and considerable expertise is required for analysis of the trace It is usually not practical to undertake traditional EEG recordings at the time the baby shows abnormal movements More recently various technological developments have allowed more direct investigation of neuronal electrical activity by either video-EEG or compressed recording of the amplitude integrated EEG (aEEG or CFM)
Rennie et al3 at Kingrsquos College Hospital London have under-taken extensive evaluation of video-EEG and have found that this technique detects many convulsions not recognized by a single channel aEEG or CFM trace Of 19 infants with evidence of convulsions on EEG only four were recognized on CFM but this may have been due to the observersrsquo lack of experi-ence with this technique In other centres that have developed appropriate expertise aEEG or CFM has proved more sensitive to the detection of seizures Video-EEG studies have also shown that many movements interpreted by experienced clinicians to be seizures are not associated with abnormal cortical activity Conversely many electrical seizures are not associated with abnormal movements This is referred to as electroconvulsive dissociation
In summary clinical observation alone to detect the fitting baby is unreliable in that it may either over-detect seizure activ-ity which is not present on EEG or under-detect clinical seizures in infants with EEG-proven convulsions The decision as to which babies to treat with antiepileptic drugs therefore becomes somewhat arbitrary
Do anticonvulsants stop neonatal seizuresAlthough neonatal seizures are common there are few random-ized controlled trials assessing the benefits of antiepileptic drugs (AEDs) in the treatment of this condition Phenobarbitone is the most widely used first-line AED and in an Australasian study 95 of neonatologists and paediatric neurologists used this drug as first-line management12 The most commonly used loading dosage is 20 mgkg but regimens of up to 40 mgkg have been recommended (Table 3)13 Four trials have evaluated the effect of phenobarbitone in abolishing neonatal seizures Two of these studies used EEG to monitor response to the drug1415 and one compared phenobarbitone with phenytoin15 In the latter study seizures were completely controlled in only 43 of babies and in the group where phenytoin was the first drug used com-plete seizure control was achieved in 45 This study switched babies from their first AED to the other if complete control was not obtained on EEG monitoring after exposure to first-line therapy In babies who had been given phenobarbitone as first-line therapy seizure control was only achieved in 57 after phenytoin was added In those given phenytoin first complete
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
Dosage regimens for first- second- and third-line anticonvulsants in the neonatal period
Loading dose Second loading dose if first
unsuccessfulMaintenance dose
phenobarbitone 20 mgkg by slow iv injection 10 mgkg iv 25ndash5 mgkg od
phenytoin 20 mgkg iv over 20 min not recommended
midazolam 150ndash200 μgkg iv infusion 1 μgkgmin iv infusion increasing to 5 μgkgmin
until favourable response
lidocaine 2 mgkg iv over 10 min 6 mgkgh for 6 h iv then 4 mgkgh for 12 h then
2 mgkgh for 12 h
lorazepam 005ndash01 mgkg by slow iv injection
Diazepam 03ndash04 mgkg iv over 3ndash5 min
lidocaine should not be used if the infant has previously been treated with phenytoin
Table 3
seizure control was achieved with the adding of phenobarbitone in 62
Boylan et al14 assessed the efficacy of phenobarbitone (20ndash40 mgkg iv over 20 min) in 14 babies monitored by video-EEG in only four was there complete abolition of seizures and in the other 10 electroconvulsive seizure activity increased whereas clinical evidence of seizures reduced This has been termed elec-troclinical dissociation and anticonvulsant drug use in the new-born appears to increase this feature They also showed that the babies least likely to respond to the first-line AED are those with the most abnormal background EEG
Two studies have evaluated the use of phenobarbitone in babies who had sustained significant asphyxial insult at birth Hall et al13 compared high-dose phenobarbitone (mean 39 mgkg) versus standard dose (27 mgkg) and reported fewer convul-sions and a significant reduction of severe disability or death in the high dose group (RR 030 CI 010ndash093) A recent study from India16 of babies with hypoxicndashischaemic encephalopathy ran-domized 25 babies to phenobarbitone (20 mgkg loading dose) and compared them with 20 control babies Only 2 of 25 (4) in the phenobarbitone group developed convulsions compared with 8 of 20 (40) in the control group (p = 001) Because of the specific enrolment criteria (asphyxial insult) neither of these studies is strictly comparable to the studies by Painter et al15 and Boylan et al14 whose intention was to assess the efficacy of first-line anticonvulsant therapy on convulsions of any cause diagnosed either clinically or by EEG
Other anticonvulsants used as second- and third-line drugs have been subject to few studies in the newborn Midazolam is administered as a bolus followed by continuous infusion A recent study17 has shown that in 10 of 13 neonates given intravenous midazolam for status epilepticus control of electri-cal seizures was achieved within the first hour of treatment having been previously shown to be refractory to phenobarbi-tone treatment Some of these babies required a second bolus infusion of midazolam to obtain control of all electrographic seizures
In some parts of Europe lidocaine is used as a third-line anti-convulsant Malingre et al18 evaluated 20 infants refractory to
paeDiatRiCS anD CHilD HealtH 184 180
both phenobarbitone and midazolam and who were then given lidocaine by continuous infusion Lidocaine was effective in abolishing electroconvulsive seizures diagnosed by aEEG in 76 of the treatment courses studied No babies developed cardiac arrhythmias a previously reported complication of lidocaine in older patients As a result of pharmacokinetic studies the dosage regimen has been modified (see Table 3)
In summary phenobarbitone is effective in seizure control in less than 50 of babies and even when combined with phe-nytoin the efficacy of these drugs together remains poor More worrying is the observation that phenobarbitone tends to reduce clinically evident seizures thereby giving the clinician a false sense of security whilst having little or no effect on the num-bers of electroconvulsive disorders This has been summarized appropriately as lsquoafter all these years we still love what doesnrsquot workrsquo19 Both midazolam and lidocaine infusions appear to be effective in abolishing severe seizures in some infants resistant to phenobarbitone Lidocaine should not be given to babies previ-ously exposed to phenytoin for fear of a synergistic adverse effect on cardiac rhythm
Do antiepileptic drugs cause brain damageA riskndashbenefit analysis is needed to evaluate the efficacy of anticonvulsants in stopping neonatal seizures which is poor with standard anticonvulsants as discussed above against the risk of administering the anticonvulsant drugs themselves Phenobarbitone has been reported to have adverse effects on the developing brain including inhibition of brain growth20 neuronal toxicity21 and adverse behavioural and cognitive effects into adult life when administered to young animals22 Phenytoin shows unpredictable plasma levels and potential cardiotoxicity
Recent studies have shown an effect of AED exposure on the developing brain by causing neurodegeneration23 Phenytoin administration to immature rat pups at doses which produce serum levels similar to those achieved in human neonates was associated with widespread neuronal death as a result of apop-tosis (programmed cell death) Phenobarbitone had a similar effect when a dosage regimen similar to 40 mgkg was used and
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
this effect was maximal in the more immature brain Diazepam and clonazepam also resulted in a similar effect Midazolam and lidocaine were not tested in this study The combination of phenobarbitone or phenytoin with diazepam had a particularly profound effect on neurodegeneration
In summary recent data suggest that the commonly used AEDs for neonatal convulsions may in themselves cause neuro-degeneration due to apoptosis with lasting effects on develop-ment Many babies with neonatal convulsions are treated with at least two AEDs and this may produce more severe adverse effects than the seizures themselves
Practical management of neonatal seizures
Assimilation of these data and formulation of a rational policy is difficult when faced with a fitting neonate on an intensive care unit and pressure on the medical staff to lsquodo somethingrsquo but it is important to accept that sometimes doing nothing is preferable to using potentially dangerous drugs in a situation which does not warrant such intervention Many babies who have normal interseizure neurological clinical findings and whose seizures are relatively brief and infrequent probably do not need anticon-vulsant medication A normal or near-normal background EEG trace should reassure the clinician that anticonvulsants can be withheld
Some causes of neonatal convulsions are treatable such as meningitis hypoglycaemia hypocalcaemia and inborn errors of metabolism and each baby should be rapidly and carefully investigated for cause of the convulsions
In some babies clinical assessment of seizures is difficult ie when the baby is very sick small or paralyzed Sometimes it may be difficult to assess the significance of certain movement pat-terns Under these circumstances an EEG may prove to be very helpful In many units EEG is not available out of hours and a simple aEEG or CFM is strongly advised Modern instruments are very simple to apply and prolonged or frequent seizures should be identified with only moderate training The printout can be faxed to a more senior doctor if there is doubt as to what is shown on the trace
The balance of knowledge now is that frequent seizures cause additional damage to the developing brain and that treatment to abolish the seizures is warranted Unfortunately there is little evidence that the majority of seizures can be effectively termi-nated by current standard therapy Furthermore it appears that the more abnormal the background EEG the more difficult it is to control the seizures Nevertheless a written protocol for the management of neonatal convulsions is required on each unit Phenobarbitone and phenytoin remain the mainstay of treat-ment although their effectiveness is disappointing There is little to suggest that midazolam is more effective than lidocaine as third-line therapy but lidocaine is precluded if phenytoin has been previously used
In view of the anxiety as to the neurodegenerative effects on the immature brain of most anticonvulsants used in the neonatal period (particularly when multiple drugs are used) it is prefer-able to use only one drug to maximum dosage before introduc-ing a second In addition the duration of anticonvulsants should be minimized and the drugs stopped at the earliest opportu-nity It is my practice to stop anticonvulsants prior to discharge
paeDiatRiCS anD CHilD HealtH 184 18
from hospital if the baby is neurologically normal on clinical examination
REFEREnCES
1 Ronen gm penney S andrews W the epidemiology of clinical
neonatal seizures in newfoundland a population-based study
J Pediatr 1999 134 71ndash75
2 lanska mJ lanska DJ Baumann RJ et al a population-based study
of neonatal seizures in Fayette County Kentucky Neurology 1995
45 724ndash732
3 Rennie Jm Chorley g Boylan gB et al non-expert use of the
cerebral function monitor for neonatal seizure detection Arch Dis
Child Fetal Neonatal Ed 2004 89 F37ndashF40
4 tekgul H gauvreau K Soul J et al the current etoliologic profile
and neurodevelopmental outcome of seizures in term newborn
infants Pediatrics 2006 117 1270ndash1280
5 Surtees R Wolf n treatable neonatal epilepsy Arch Dis Child 2007
92 659ndash661
6 Ben-ari y Holmes gl effects of seizures on developmental
processes in the immature brain Lancet Neurol 2006 5 1055ndash
1063
7 Holmes gl gairsa Jl Chevassus-au-louis n et al Consequences of
neonatal seizures in the rat morphological and behavioral effects
Ann Neurol 1998 44 845ndash857
8 Stafstrom Ce Chronopoulos a thurber S et al age-dependent
cognitive and behavioural deficits following kainic-acid inducing
seizures Epilepsia 1993 34 420ndash432
9 Schmid R tandon p Stafstrom Ce et al effects of neonatal seizures
on subsequent seizure-induced brain injury Neurology 1999 53
1754ndash1761
10 Hoffmann aF Zhao Q Holmes gl Cognitive impairment following
status epilepticus and recurrent seizures during early development
support for the ldquotwo-hit hypothesisrdquo Epilepsy Behav 2004 5
873ndash877
11 Wirrell eC armstrong ea osman lD et al prolonged seizures
exacerbate perinatal hypoxic-ischemic brain damage Pediatr Res
2001 50 445ndash454
12 Carmo KB Barr p Drug treatment of neonatal seizures by
neonatologists and paediatric neurologists J Paediatr Child Health
2005 41 313ndash316
13 Hall Rt Hall FK Daily DK High-dose phenobarbital therapy in term
newborn infants with severe perinatal asphyxia a randomized
prospective study with three-year follow-up J Pediatr 1998 132
345ndash348
14 Boylan gB Rennie Jm pressler Rm et al phenobarbitone neonatal
seizures and video-eeg Arch Dis Child Fetal Neonatal Ed 2002 86
F165ndash170
15 painter mJ Scher mS Stein aD et al phenobarbital compared with
phenytoin for the treatment of neonatal seizures N Engl J Med
1999 341 485ndash489
16 Singh D Kumar p narang a a randomized controlled trial of
phenobarbital in neonates with hypoxic ischemic encephalopathy
J Matern Fetal Neonatal Med 2005 18 391ndash395
17 Castro Conde JR Borges H Domenech martinez e et al midazolam
in neonatal seizures with no response to phenobarbital Neurology
2005 64 876ndash879
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
18 malingre mm Van Rooij lgm Rademaker Cma et al Development
of an optimal lidocaine infusion strategy for neonatal seizures Eur
J Pediatr 2006 165 598ndash604
19 Sankar R painter mJ neonatal seizures after all these years we still
love what doesnrsquot work Neurology 2005 64 776ndash777
20 Diaz J Schain J Bailey Bg phenobarbital-induced brain growth
retardation in artificially reared rat pups Biol Neonate 1977 32 77ndash82
21 mattson RH phenobarbital toxicity in levy RH Dreifuss Fe
mattson RH et al eds antiepipeptic Drugs 3rd edn new york
Raven 1985 p 341ndash355
22 mikati ma Holmes gl Chronopoulos a et al phenobarbital
modifies seizure-related brain injury in the developing brain Ann
Neurol 1994 36 425ndash453
23 Bittigau p Sifringer m genz K et al antiepileptic drugs and
apoptotic neurodegeneration in the developing brain Proc Natl
Acad Sci U S A 2002 99 15089ndash15094
paeDiatRiCS anD CHilD HealtH 184 182
Practice points
bull the clinician needs to be aware that almost any repetitive
stereotype movement pattern can be a manifestation of
neonatal seizures
bull eeg is important in defining neonatal seizures
bull Frequent short-lived seizures have been shown to cause long-
term neurodevelopmental problems
bull Conventional anticonvulsant medication is ineffective in
abolishing neonatal seizures in greater than 50 of cases
bull there is evidence that exposure of the neonatal brain to
multiple anticonvulsants causes neuronal death
bull Future research is needed to evaluate more effective
anticonvulsants for treating this condition
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
Emotional support for families of sick neonatesMarina nicolaou
cristine Glazebrook
AbstractParents of sick neonates experience high levels of stress anxiety and
depression Most interventions with families of sick infants have focused
on fostering the motherndashinfant relationship through the provision of
information about infant developmental needs or through increased
motherndashinfant contact Many of these studies have reported improved
maternal well-being though there are some concerns about the scope
and practicality of large-scale interventions The few studies to have
prioritized emotional support for parents of sick neonates have pro-
duced encouraging results even interventions requiring relatively few re-
sources such as telephone support parent-to-parent support and group
support have been associated with reduced psychological morbidity for
parents The needs of parents can change throughout their infantrsquos hos-
pitalization and not all want or benefit from the provision of additional
support Thus neonatal intensive care units should aim to provide a
varied flexible and sustainable programme of support options Further
research should focus on the needs of fathers
Keywords mental health neonatal intensive care parents
The admission of an infant to neonatal care is acknowledged to be a source of considerable distress for families This review aims to explore evidence for the psychological impact on families of having an infant in neonatal intensive care and to identify evi-dence for the effectiveness of interventions to promote parental well-being It will conclude with recommendations for strategies to support parents of vulnerable infants and suggestions for fur-ther research
Psychological impact of neonatal care for parents
The majority of research examining the effect on parents of having a sick neonate has focused on families of premature or low birthweight infants Such research has found that parents with a sick neonate exhibit high levels of stress compared to normative samples and to parents of healthy full-term infants1 Singer et al2 examined the stress experienced by mothers of high-risk very low birthweight (VLBW) low-risk VLBW and term
Marina Nicolaou MPhil is a Teaching Assistant at the School of
Community Health Sciences University of Nottingham Nottingham UK
Cristine Glazebrook PhD is a Professor of Health Psychology at the School
of Community Health Sciences University of Nottingham Nottingham UK
PaeDiaTrics anD cHilD HealTH 184 196
infants Several self-report measures were used including the Brief Symptom Inventory the Parenting Stress Index (PSI) the Impact on Family Scale and the Family Inventory of Life Events and Changes (FILE) Mothers of VLBW infants had more psycho-logical distress at 1 month compared to mothers of term infants Mothers of high-risk VLBW infants also reported high psycho-logical distress at 2 years and high levels of parenting stress at 3 years Mothers have also been found to have higher stress levels compared to fathers Shaw et al3 examined the prevalence of acute stress disorder (ASD) in 40 parents whose infants were in the neonatal intensive care unit (NICU) Nearly half of the moth-ers (44) met the criteria for ASD although none of the fathers did Furthermore the severity of the symptoms (measured by the number of concurrent symptoms) was greater for the moth-ers than for the fathers3 The reasons behind this difference have been widely speculated with some believing that it is due to the mothersrsquo greater psychological involvement with the infant as evidenced by their general greater vulnerability to postpartum psychological disorder It could also reflect gender differences in coping style
Having an infant who requires intensive medical care repre-sents a significant emotional burden for families Not only is there extreme anxiety surrounding the infantrsquos health and distress for the childrsquos suffering there is also the unfamiliar and intimidating environment of the NICU to adjust to Hopper in her review of the literature identified sources of stress for parents of sick neo-nates as falling into three areas4 Situational factors included the severity of the infantrsquos illness and how parents adapted to the life crisis of having a sick infant Personal factors involved parental emotions about their roles and the instrumental and informa-tional support which were available to them The third area was classified as environmental sources of stress and included the environment of the NICU and the relationship between parents and members of staff This relationship has been examined by several studies in the nursing literature nurses are seen as ide-ally placed to provide the necessary support and information to parents with sick neonates However whilst some studies have shown that supportive and helpful hospital staff can have a posi-tive effect on parents other studies have highlighted the prob-lems and difficulties which can manifest It has been shown that parents and nurses often have very different ideas about issues eg the necessary skills and competencies needed in an NICU or the characteristics that make a lsquogood motherrsquo
Research has shown that there may be a relationship between high levels of parental stress and an increased likelihood of depression5 Postpartum depression is a psychiatric illness which appears in 10ndash15 of postpartum women Its reported preva-lence rates however have ranged from less than 10 up to 306 depending on the instruments used the population exam-ined and the timing of the research Several factors have been found to be associated with postpartum depression including poor social support and infant-related stressors6 Evidence indi-cates that postnatal depression may be underreported and this is of concern since the mental and psychological health of the mother can affect her relationship with her infant and thus the infantrsquos cognitive and emotional development5 Depressed moth-ers appear to look touch and talk to their infants less frequently and also appear to show fewer positive and more negative faces7 The vocalizations of mothers suffering with depression have also
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
been found to be less effective at promoting cognitive growth and learning in infants8
If researchers are interested in finding ways of providing sup-port for families of sick neonates then they must listen to what such families perceive their needs to be in order to avoid increas-ing anxiety and distress Furthermore the provision of appropri-ate support be it emotional informational or social will enhance parental coping abilities increase self-esteem and reduce anxiety It should be noted though that the research conducted around these issues has often taken lsquosupport needsrsquo as being synony-mous with lsquoinformation needsrsquo Such studies have examined the type the amount and quality of information that parents receive and perceive themselves as needing but have not explored in equal depth the perceived emotional support needs of families who have a sick infant In addition the needs of parents may change throughout their infantrsquos illness Ward examined the per-ceived needs of 52 parents of infants in an NICU9 Parents rated the needs of their hospitalized infant as most important along with the need to be reassured Interestingly they ranked their support needs as least important This research was conducted during the first week of the infantsrsquo hospitalization however which would explain the preoccupation of the parents with the infantrsquos health These results demonstrate that if researchers want to find ways of providing emotional support to parents of sick neonates they must be prepared not only to listen to parents but also to be flexible enough to satisfy the parentsrsquo changing needs and expectations
Interventions aimed at supporting parents
Most interventions that been evaluated in controlled studies have focused on supporting the motherndashinfant relationship and provid-ing information on infant development Many of these interven-tions have included the aim of improving the parental emotional state and thus psychological outcomes such as stress or anxi-ety have been assessed However few studies appear to include fathers This means that strategies implemented to provide emo-tional support to families of sick neonates are often derived from interventions tailored for mothers even though fathers may have different emotional needs
A wide range of interventions with mothers and infants has been evaluated in the NICU Increasing motherndashinfant contact through kangaroo care has been found to reduce maternal anxiety1011 and educational programmes delivered to fami-lies in the NICU have also been associated with reduced emo-tional difficulties in parents12ndash14 Kaaresen and colleagues implemented an intervention which consisted of eight sessions before discharge and four home visits all by trained nurses The sample included 71 premature infants in the intervention group 69 premature infants in the control group and 74 infants in the full-term control group The randomized controlled trial found that the intervention reduced parenting stress in both mothers and fathers of premature infants compared to controls to a level equivalent to parents in the term control group13 At 6 months corrected age mothers of preterm infants who had not received the intervention had total PSI scores which were 17 points higher than the mothers of infants born at term (an effect size of 057) A similar study evaluated the efficacy of an educationalndashbehavioural programmendashCreating Opportunities for
PaeDiaTrics anD cHilD HealTH 184 19
Parent Empowerment (COPE) ndash through a randomized controlled trial with 260 families of premature infants14 COPE was a four-phase educationalndashbehavioural programme which began as early as 2ndash4 d after mothers had given birth and continued until 1 week after discharge from the NICU The programme consisted of audiotaped and written infant behaviour information along with photographs which focused on common behaviours and characteristics of premature infants It also included various par-ent activities in the form of a four-phase workbook which aimed to assist mothers in the implementation of the experimental infor-mation COPE was found significantly to reduce maternal stress in the NICU as well as maternal anxiety and depressive symptoms after hospitalization In contrast a cluster randomized trial of a parenting intervention delivered to mothers of very premature infants from soon after birth showed no benefits for parenting stress1 The authors hypothesized that the intervention had not been of sufficient intensity particularly in the weeks surrounding discharge Neonatal care presents a significant barrier to parent-ing in the early weeks following a very preterm birth and so inter-ventions which focus on the developmental needs of infants and the parentndashchild relationship should particularly aim to support parents as they take on the parenting role There was also concern that the intervention had failed to reach those most at risk
Since large-scale projects can be costly to implement and may often fail to reach the families in most need it may be wiser to focus on intervention programmes which are more practical and easier to implement within a neonatal care setting Research has shown that even interventions which are based on one-off meet-ings with parents of sick neonates can be effective Jotzo and Poets examined the effect of an intervention programme aimed at reducing the severity of traumatic responses as a result of giv-ing birth prematurely15 Their programme consisted of a one-off intervention meeting along with additional psychological help throughout the hospitalization of the infant The meeting cov-ered a variety of issues including a reconstruction of the events shortly before and after the infantrsquos birth relaxation techniques discussion of coping strategies available resources and social support and support during emotional outbursts The measures used included the Impact of Event Scale (IES) and the Peritrau-matic Dissociative Experience Questionnaire At discharge the mothers who received the intervention were found to have a significantly lower traumatic impact as a result of premature birth Furthermore fewer mothers in the intervention group showed symptoms of clinically significant psychological trauma at discharge compared to mothers in the control group (36 vs 76)15 The lsquoParents Circle Programrsquo is another intervention with a similar structure16 This consisted of a 90 min session for parents with the aim of enhancing the developing relationship between parents and infants and to offer parents support A total of 104 parents (59 mothers and 45 fathers) and 44 members of hospital staff were asked to evaluate the programme and their results were analysed using content analysis Families reported gaining perspective on their situation feeling supported becom-ing aware of cues and optimizing interactions and becoming aware of available resources Parents and staff alike felt that participating in the intervention helped parents overcome the difficulties associated with the early time of their infantrsquos hos-pitalization Additional studies have also found positive results with fairly minimal interventions including discussion groups
7 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
in the NICU music during kangaroo care and pairing mothers of sick neonates with trained mothers who had been through similar experiences
Parent support programmes
Parent support programmes (PSPs) which are based in NICUs can provide parents with the opportunity to talk to parents who have been in similar situations and also to discuss their emo-tions with professionals who can help them cope with their situa-tion111718 The parent-to-parent support programme for mothers of preterm infants evaluated by Preyde and Ardal included edu-cational parental support group meetings and individual par-ent-to-parent support (primarily telephone support)19 Measures used included the Parental Stressor Scale NICU the State and the Trait Anxiety Inventories and the Beck Depression Inven-tory After 4 months of participation mothers in the intervention group reported lower levels of stress state anxiety and depres-sion compared to control group mothers The authors speculated however that the participants who were able to meet face to face with other parents were those who benefited the most Hurst conducted a comprehensive survey of an NICU-based PSP This PSP was provided in a variety of formats including a weekly parent support group hospital visitation and 24-h telephone sup-port20 Of the 477 participants 303 families used the PSP dur-ing a 2-year evaluation period with 78 using only one form of support and 18 using two forms Of a sub-sample of 48 parents asked to complete an evaluation of the PSP 92 stated that they would recommend such a programme to other parents Furthermore the majority of parents felt that it made them feel supported and helped them deal with their emotions20 This is an indication that such programmes can be very successful in sup-porting parents throughout their infantrsquos hospitalization It also shows that it can be beneficial to give parents several options and formats when it comes to such support services It is impor-tant to consider though that both the Hurst and the Preyde and Ardal studies found that some participants did not find the sup-port programmes helpful even reporting that they had caused them increased stress and anxiety Therefore it should not be assumed that support programmes will suit every individual and will provide the required support for all parents1920 NICUs need to be flexible enough to provide parents with a range of forms of support to choose from
The increased understanding of the strains that parents of sick neonates have to deal with has also led to efforts to improve customary practices in NICUs Family-centred care focuses on infants and their needs and attempts to redefine the relationship between parents and caregivers These practices strive to provide parents with support during their infantrsquos illness by focusing on freely sharing information and on the collaboration between parents and hospital staff Family-centred care has been found to be associated with several beneficial outcomes including improved parental satisfaction increased parental comfort staff satisfaction and decreased parental stress18 Research is already examining these practices and questioning how these can be improved further Such research reflects the increasing effort focused on lsquohumanizingrsquo the environment in NICUs in order to make parents feel more comfortable about spending time with their infants
PaeDiaTrics anD cHilD HealTH 184 19
Conclusion
Surprisingly few interventions have prioritized the provision of emotional support for parents of sick neonates or accounted for the changing needs and wishes of parents over the course of their infantrsquos care Large-scale supportive education-based inter-ventions have been shown to be effective in reducing parental distress However the feasibility and sustainability of such pro-grammes should also be considered Programmes which require significant additional resources can be expensive and there are also issues of training and quality control Interventions which require significant input from parents may also place additional burdens on families making them potentially less accessible to those most at risk Arguably the aim should be to explore ways of providing acceptable and effective informational support which could be complemented by emotional support from health professionals and from other parents in the unit Increasingly studies are exploring the use of computers and multimedia as an engaging flexible and cost-effective method of targeting indi-vidual needs and providing support and information Such com-puter-based and interactive multimedia interventions have been found to be successful with a range of patient groups and could therefore be examined as a complementary method of providing informational support to families with sick neonates
REfEREnCEs
1 Glazebrook c Marlow n israel c et al randomised trial of a
parenting intervention during neonatal intensive care Arch Dis Child
Fetal Neonatal Ed 2007 92 F438ndash443
2 singer lT salvator a Guo s collin M lilien l Baley J Maternal
psychological distress and parenting stress after the birth of a very
low-birth-weight infant JAMA 1999 281 799ndash805
3 shaw rJ Deblois T ikuta l Ginzburg K Fleisher B Koopman c
acute stress disorder among parents of infants in the neonatal
intensive care nursery Psychosomatics 2006 47 206ndash212
4 Hopper a sources of stress for parents of a sick neonate a
literature review Pediatr Nurs 2000 30 29ndash32
5 Davis l edwards H Mohay H wollin J The impact of very
premature birth on the psychological health of mothers Early Hum
Dev 2003 73 61ndash70
6 Bernazzani O saucier J-F David H Borgeat F Psychosocial
predictors of depressive symptomatology level in postpartum
women J Affect Disord 1997 46 39ndash49
7 Field T infants of depressed mothers Infant Behav Dev 1995 18
1ndash13
8 Kaplan Ps Bachorowski J-a Zarlengo-strouse P child-directed
speech produced by mothers with symptoms of depression fails
to promote associative learning in 4-month-old infants Child Dev
1999 70 560ndash570
9 ward K Perceived needs of parents of critically ill infants in
a neonatal intensive care unit (nicU) Pediatr Nurs 2001 27
281ndash286
10 lai Hl chen cJ Peng Tc et al randomized controlled trial of music
during kangaroo care on maternal state anxiety and preterm infantsrsquo
responses Int J Nurs Stud 2006 43 139ndash146
8 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
11 Tallandini Ma scalembra c Kangaroo mother care and mother-
premature infant dyadic interaction Infant Ment Health J 2006 27
251ndash275
12 Ohgi s Fukuda M akiyama T Gima H effect of an early intervention
programme on low birthweight infants with cerebral injuries
J Paediatr Child Health 2004 40 689ndash695
13 Kaaresen Pi ronning Ja Ulvund se Dahl lB a randomized
controlled trial of the effectiveness of an early-intervention program
in reducing parenting stress after preterm birth Pediatrics 2006
118 e9ndash19
14 Melnyk BM Feinstein nF alpert-Gillis l et al reducing premature
infantsrsquo length of stay and improving parentsrsquo mental health
outcomes with the creating opportunities for parent empowerment
(cOPe) neonatal intensive care unit program a randomized
controlled trial Pediatrics 2006 118 e1414ndash1427
15 Jotzo M Poets cF Helping parents cope with the trauma of
premature birth an evaluation of a trauma-preventive psychological
intervention Pediatrics 2005 115 915ndash919
16 Pearson J andersen K evaluation of a program to promote positive
parenting in the neonatal intensive care unit Neonatal Netw 2001
20 43ndash48
17 roman l lindsay J Boger r et al Parent-to-parent support
initiated in the neonatal intensive care unit Res Nurs Health 1995
18 385ndash394
18 Meyer ec coll cTG lester BM Boukydis cFZ McDonough sM Oh w
Family-based intervention improves maternal psychological well-
being and feeding interaction of preterm infants Pediatrics 1994
93 241ndash246
PaeDiaTrics anD cHilD HealTH 184 19
19 Preyde M ardal F effectiveness of a parent ldquobuddyrdquo program for
mothers of very preterm infants in a neonatal intensive care unit
CMAJ 2003 168 969ndash973
20 Hurst i One size does not fit all Parentsrsquo evaluations of a support
program in a newborn intensive care nursery J Perinat Neonatal
Nurs 2006 20 252ndash261
Practice points
bull Parents of sick neonates experience significant distress and
exhibit higher levels of stress anxiety and depression than
parents of healthy infants
bull educational support emotional support and increased
motherndashinfant contact have been shown to promote maternal
well-being
bull emotional support for fathers has been largely neglected in
the research literature
bull Parents benefit from a choice of supportive facilities which
could include face-to-face sessions with health professionals
telephone support hospital visitation parent-to-parent
support and unit-based group support meetings
bull Parentsrsquo support needs can change during their infantrsquos
hospitalization and not all parents want or benefit from the
provision of additional information and emotional support in
the neonatal unit
9 copy 2008 elsevier ltd all rights reserved
Personal Practice
When should enteral feeds be started in preterm infantsnicholas D embleton
AbstractPaediatricians are regularly faced with the question of when best to start
enteral feeds in preterm infants this is important as longer term out-
come may be compromised by sub-optimal nutrition in early life clinical
factors that may affect the decision to start and the risk and benefits
are discussed
Keywords breast milk feeding nutrition parenteral nutrition
Key points in the history
Alice is lsquonutritionally vulnerablersquo and whilst this may not be immediately apparent it will affect her long term outcome Her energy stores are extremely limited and consist primarily of pro-tein She has less than 5 fat and little energy associated with stored glycogen She is losing about 1 gkgd protein equivalent so she needs at least that and a minimum of 50ndash60 kcalkg of energy just to maintain the status quo let alone grow
Her weight is on the 25th centile Review of any antenatal his-tory may reveal whether fetal growth was normal Fetal growth retardation can occur with a weight greater than 10th centile The presence of antenatal absent or reversed end diastolic flow in the umbilical artery indicates poor gut blood flow This increases the risk of necrotizing enterocolitis (NEC) and might suggest a more cautious approach to starting feeds1
She has no important cardiovascular problems but if she were hypotensive gut blood flow may be low There is no umbilical
Nicholas D Embleton BSC (Hons) MBBS (Hons) MD FRCPCH is Consultant in
Neonatal Medicine at Newcastle Neonatal Service Royal Victoria
Infirmary Newcastle upon Tyne NE1 4LP UK
Should you start feeds at a day of age
alice was born following spontaneous labour at 30 weeksrsquo
gestation she weighed 1300 g and is now 18 h old she was
briefly ventilated and then extubated to continuous positive
airway pressure 12 h ago in 35 oxygen she has had caffeine
citrate but still has intermittent episodes of self-correcting
apnoea she was commenced on iv 10 dextrose but this was
replaced by a parenteral amino acid solution (referred to as
lsquotPnrsquo) along with intralipid at 0900 this morning serum glucose
is 11 mmoll and blood pressure is 42 systolic
PaeDiatrics anD cHilD HealtH 184 20
arterial catheter in situ but there is no good evidence that this should delay the decision to start feeds Her glucose is high but this is quite common in a baby like this Could this be a sign of sepsis Caffeine does not affect the incidence of NEC2 The great-est risk factor for NEC in this case is prematurity
What else might be found on examination
Up until 24 h ago she was swallowing large amounts of amniotic fluid What will have changed since then
General examination should confirm peripheral perfusion lsquogestaltrsquo view (does she look lsquowellrsquo) and cardiovascular status lsquoBowel soundsrsquo are not usually helpful
The most important variable likely to affect gut perfusion is the arterial duct Precordial lsquoheaversquo and a loud murmur are sug-gestive but it is possible to have a significant ductal shunt in a baby with a normal examination Cardiac ultrasound will con-firm this diagnosis It might be better to treat a large shunt first with indometacin and to delay starting feeds for a further 24 h
It is not possible to assess gut perfusion clinically but normal perfusion elsewhere (adequate urine output usually indicates adequate renal perfusion) would be reassuring Most preterm babies have a few abdominal lsquoloopsrsquo visible but a distended abdomen with many palpable loops suggests ileus This might be secondary to sepsis or poor gut blood flow Preterm babies do not pass much meconium in the first 24ndash48 h
Balance of risks between starting and withholding feeds
Alice requires 35ndash4 gkgd of protein and 120 kcalkgd to grow3 This will initially be provided parenterally Delaying feeds increases the risk of gut villous atrophy and prolongs the need for lsquototal parenteral nutrition (TPN)rsquo TPN requires intravenous access and so increases the risk of sepsis and when prolonged use is required combined with the lack of enteral feeding may result in hepatic impairment
Delaying feeds may allow a gut that has been chronically under-perfused to re-establish more normal perfusion although normal gut endocrine function digestive enzyme upregulation and motility require a source of intraluminal nutrients1 A recent study suggested benefit from delaying the introduction of feeds4 but methodologi-cal problems exist5 Although a Cochrane meta-analysis suggested no benefit only two studies were included6 A large UK-based trial is examining the effect of early or late feeding in preterm infants who were born growth retarded following identification of antena-tal absent or reversed end diastolic flow in the umbilical artery7
When starting feeds what volume should be used
There are no good data to guide this decision We start with 24 mlkg (1 mlkgh) and then increase by this amount each day Most babies achieve full enteral feeds (ge150 mlkgd) by a week of age Feeding guidelines improve the outcome8 Measure-ment or assessment of gastric aspirates is not consistently useful in predicting subsequent feeding intolerance or development of NEC Aspirate volumes equivalent to or sometimes greater than the amount given in the preceding 1ndash2 h are usually normal Most aspirates have a greenish colour Thick bloody or intensely bile-stained aspirates require detailed assessment
0 copy 2008 elsevier ltd all rights reserved
Personal Practice
What else affects decisions and outcome
Feeding success is affected by sepsis and NEC Scrupulous atten-tion should be paid to hand washing and intravenous access and blood sampling should be minimized There is no good evidence to support the routine use of pro-kinetic agents or H2 blockers
The most important clinical intervention affecting the occur-rence of NEC is the use of breast milk9 All efforts should be directed at persuading parents of the benefits and supporting the process Some clinicians delay starting feeds for a further 24 h whilst expressed breast milk becomes available Donor breast milk might be equally efficacious10
RefeRenceS
1 Dorling J Kempley s leaf a Feeding growth restricted preterm
infants with abnormal antenatal Doppler results Arch Dis Child Fetal
Neonatal Ed 2005 90 F359ndash363
2 schmidt B roberts rs Davis P et al caffeine therapy for apnea of
prematurity N Engl J Med 2006 354 2112ndash2121
PaeDiatrics anD cHilD HealtH 184 20
3 embleton nD Pang n cooke rJ Postnatal malnutrition and growth
retardation an inevitable consequence of current recommendations
in preterm infants Pediatrics 2001 107 270ndash273
4 Berseth cl Bisquera Ja Paje VU Prolonging small feeding volumes
early in life decreases the incidence of necrotizing enterocolitis in
very low birth weight infants Pediatrics 2003 111 529ndash534
5 Menon G Boyle eM embleton nD et al introduction of enteral
feeds in preterm infants Pediatrics 2004 114 327ndash328
6 Kennedy Ka tyson Je chamnanvanikij s early versus delayed
initiation of progressive enteral feedings for parenterally fed low
birth weight or preterm infants Cochrane Database Syst Rev 2000
cD001970
7 wwwnpeuoxacukadept
8 Patole sK de Klerk n impact of standardised feeding regimens on
incidence of neonatal necrotising enterocolitis a systematic review
and meta-analysis of observational studies Arch Dis Child Fetal
Neonatal Ed 2005 90 F147ndash151
9 lucas a cole tJ Breast milk and neonatal necrotising enterocolitis
Lancet 1990 336 1519ndash1523
10 Boyd ca Quigley Ma Brocklehurst P Donor breast milk versus
infant formula for preterm infants systematic review and meta-
analysis Arch Dis Child Fetal Neonatal Ed 2007 92 F169ndash175
1 copy 2008 elsevier ltd all rights reserved
self-assessment
Case 1A term male infant born to consanguineous parents is assessed at 24 h of age due to poor feeding profuse yellow watery diar-rhoea and irritability He weighed 32 kg at birth and delivery was uneventful There was no polyhydramnios He has been breastfed since birth On examination he is pale with a non-tender but distended abdomen and reduced bowel sounds His weight is 275 kg and he looks dehydrated Examination is otherwise normal
Initial investigations (normal values in parentheses) showed
sodium 149 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 65 mmollitre (25ndash75)
creatinine 147 μmollitre (40ndash110)
chloride 119 mmollitre (95ndash105)
haemoglobin 172 gdl (140ndash200)
White blood cell count 80 times 109litre (100ndash260)
Platelet count 302 times 109litre (150ndash400)
arterial blood gas
ph 720 (730ndash745)
PcO2 23 kPa (46ndash60)
Bicarbonate 68 mmollitre (220ndash260)
Base excess minus186 mmollitre (minus20 to +20)
lactate 59 mmollitre (06ndash24)
An abdominal X-ray shows distended bowel loops with no intramural thickening or pneumoperitoneum (Figure 1)
He was given nil by mouth and received intravenous fluids and antibiotics His dehydration improved but the metabolic acidosis and diarrhoea persisted despite receiving no enteral feeds and the commencement of total parenteral nutrition Blood and stool cultures were negative
1 Which of the following best describes these results Choose ONE answer ONLY from the followingA Hypernatraemia hyperchloraemic metabolic acidosis
with increased anion gapB Hypernatraemia hyperchloraemic metabolic acidosis
with normal anion gap
Manish Sadarangani BM BCh MA MRCPCH is Clinical Research Fellow
at the Department of Paediatrics University of Oxford Centre for
Clinical Vaccinology and Tropical Medicine Churchill Hospital
Oxford OX3 7LJ UK
Shabna Rajapaksa MB BChir MA MRCPCH is Specialist Registrar in
Paediatrics at the Paediatric Intensive Care Unit John Radcliffe
Hospital Oxford OX3 9DU UK
Nicholas Mann MD FRCP FRCPCH DCH is Consultant Paediatrician at the
Department of Paediatrics Royal Berkshire Hospital Reading RG1
5AN UK
self-assessment
C Hypernatraemic dehydration and compensated metabolic acidosis
D Acute renal failureE Renal tubular acidosis
2 What is the likely diagnosis Choose ONE answer ONLY from the followingA Hirschsprung disease ndash long segmentB Cystic fibrosis with meconium ileusC Microvillus inclusion diseaseD Cowrsquos milk protein intoleranceE Lactose intolerance
3 What is the investigation of choice Choose ONE answer ONLY from the followingA Rectal biopsy with staining for acetylcholine receptorsB Immunoreactive trypsinC Gastrointestinal endoscopy and biopsyD Stool microscopy and cultureE Stool reducing substances
Case 2A 4-year-old boy presents with a 3 d history of jaundice and a florid rash He has had orange urine and there is no change in his stool colour His family originate from Kosovo and have lived in the UK for the last 8 years He has never left the UK There is no history of blood transfusion or sex-ual abuse The grandmother was recently diagnosed with hepatitis B
On examination he is well apyrexial and mildly jaundiced with cervical and axillary lymphadenopathy He has an exten-sive papular rash over the face extremities and trunk (Figure 2) There is 3 cm hepatomegaly with no splenomegaly or ascites Examination is otherwise normal
Figure 1 abdominal X-ray of baby
Paediatrics and child health 184 202 copy 2008 elsevier ltd all rights reserved
self-assessment
Initial investigations are as follows
haemoglobin 110 gdl (113ndash135)
White blood cell count 108 times 109litre (50ndash150)
Platelet count 278 times 109litre (150ndash400)
inr 10 (08ndash12)
aPt ratio 10 (08ndash13)
sodium 140 mmollitre (135ndash145)
Potassium 42 mmollitre (35ndash50)
Urea 56 mmollitre (25ndash75)
creatinine 65 μmollitre (45ndash120)
total bilirubin 66 μmollitre (0ndash15)
conjugated bilirubin 23 μmollitre (0ndash10)
alanine aminotransferase (alt) 2033 iUlitre (0ndash35)
alkaline phosphatase 987 iUlitre (71ndash234)
Gamma-glutamyl transferase (GGt) 870 iUlitre (0ndash51)
1 What is the name of this rash Choose ONE answer ONLY from the followingA Erythema multiformeB Erythema migransC GianottiminusCrosti syndromeD EczemaE Dermatitis herpetiformis
2 What is the most likely diagnosis Choose ONE Answer ONLY from the followingA Autoimmune hepatitisB Hepatitis BC Hepatitis DD Wilson diseaseE Alpha-1 antitrypsin deficiency
3 What is the best means of management Choose ONE answer ONLY from the followingA Isolation until the jaundice disappearsB ImmunosuppressionC Copper chelating agents and genetic counsellingD Patient and family education with consideration of
antiviral agentsE Liver transplantation
Case 3A 10-month-old boy presents with 3 weeks of vomiting and constipation ndash he is passing hard stools every 2ndash3 days He has fallen from the 9th to below the 04th centile in the last 6 weeks He passed meconium within the first 24 h of life On examina-tion he looks pale and there are some dysmorphic features ndash a short nose long philtrum and wide mouth He has normal heart sounds with a grade 3 ejection systolic murmur loudest at the upper right sternal edge Examination is otherwise normal
Initial investigations are as follows
haemoglobin 91 gdl (113ndash141)
total white blood cell count 124 times 109litre (60ndash170)
Platelet count 407 times 109litre (150ndash400)
sodium 144 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 78 mmollitre (25ndash75)
creatinine 78 μmollitre (45ndash120)
albumin 52 glitre (35ndash50)
corrected calcium 384 mmollitre (238ndash263)
Phosphate 167 mmollitre (099ndash157)
1 What is the most likely diagnosis Choose ONE answer ONLY from the followingA HyperparathyroidismB Acute leukaemiaC Williams syndromeD Hypervitaminosis DE Familial hypocalciuric hypercalcaemia
2 Which investigation would be most useful in establishing the diagnosis Choose ONE answer ONLY from the followingA Intact parathyroid hormone assayB Blood filmC Fluorescent in-situ hybridization for 7q1123 deletionD 25-hydroxyvitamin D assayE Urine calciumcreatinine ratio
3 Which of the following treatments would not be suitable for this patient Choose ONE answer ONLY from the followingA Low calcium dietB Normal saline infusionC FurosemideD CorticosteroidsE Bisphosphonates
Case 4A 10-week-old girl presents with a 2-day history of poor feed-ing Her mother has been concerned about weakness since birth She only has a flicker of movement in the arms none in the legs and has a weak cry She has been passing urine and opening her bowels normally She was born at full term by normal delivery and did not require any resuscitation at birth Normal fetal movements were felt antenatally and there was no polyhydramnios She is the first child of non- consanguineous parents and there is no significant family his-tory On examination she is alert and fixing and following appropriately She has a weak cry and a weak suck There is reduced central and peripheral tone with marked head lag
Figure 2 rash found on examination
Paediatrics and child health 184 203 copy 2008 elsevier ltd all rights reserved
self-assessment
Muscle power is grade 3 out of 5 in the arms and legs There is no muscle or tongue fasciculation and she has absent reflexes throughout The remainder of the examination is normal
Electromyogram shows irregular polyphasic motor unit potentials with marked instability consistent with a dener-vating and re-innervating process (Figure 3)
1 Which of the following additional investigations may be helpful Choose ONE answer ONLY from the followingA Nerve conduction studiesB Creatine kinase assayC Muscle biopsyD SMN1 gene analysisE All of the above
2 What is the most likely cause of this childrsquos symptoms Choose ONE answer ONLY from the followingA Congenital myotonic dystrophyB Duchenne muscular dystrophyC PraderminusWilli syndromeD Spinal muscular atrophyE Mitochondrial myopathy
3 What is the mode of inheritance of this disease Choose ONE answer ONLY from the followingA X-linked recessiveB Autosomal recessiveC Autosomal dominantD MitochondrialE Sporadic
Case 5A 13-year-old girl presents with a 3-week history of fever up to 40degC night sweats and headache She has a reduced appetite with some weight loss She has no other specific symptoms She was on holiday in China 7 months ago On examination she looks well and has a temperature of 387degC There is no lymphadenopathy and no rashes Examination is entirely normal
Results of investigations are as follows
haemoglobin 126 gdl (120ndash160)
total white blood cell count 132 times 109litre (43ndash108)
neutrophil count 115 times 109litre (25ndash75)
Platelet count 244 times 109litre (150ndash400)
Blood film neutrophilia with left shift
erythrocyte sedimentation rate 63 mmh (1ndash20)
c-reactive protein 219 mglitre (0ndash5)
Blood culture Streptococcus intermedius
from anaerobic bottle only
csf culture negative
Magnetic resonance imaging (MRI) of the brain shows acute frontal sinusitis with a large intracranial frontal extra-dural empyema (Figure 4)
1 Which of the following would be appropriate management Choose ONE answer ONLY from the followingA A 12-week course of intravenous antibioticsB Drainage of the frontal sinus followed by 2 weeks of
intravenous antibioticsC Drainage of the empyema followed by 2 weeks of
intravenous antibioticsD Drainage of the empyema and the frontal sinus
followed by 2 weeks of oral antibiotics
1151
1152
1153
1154
1155
1156
1157
1158
1159
1200
50ms 1mV
Figure 3 electromyogram recording from the patient Figure 4 Parasagittal section from mri scan of patient
Paediatrics and child health 184 204 copy 2008 elsevier ltd all rights reserved
self-assessment
E Drainage of the empyema and the frontal sinus followed by 8 weeks of intravenous antibiotics
2 Streptococcus intermedius is a potential pathogen in which of the following infections Choose ONE answer ONLY from the followingA Liver abscessB Urinary tract infectionC MeningitisD Thoracic empyemaE Pneumonia
3 Which of the following statements regarding lsquopyrexia of unknown originrsquo in children is false Choose ONE answer ONLY from the followingA Malignancy is the underlying pathology in 5ndash15 of
casesB An aetiology will be found in over 90 of casesC The most common cause is infectionD A rheumatological cause is found in 10ndash20 of casesE Familial Mediterranean fever can occur in children of
non-Mediterranean ethnicity
Answers
Case 11 AThe anion gap is a useful tool to differentiate the causes of a metabolic acidosis It is calculated by the equation
Anion gap = [Na K ] [Cl HCO ]3+ + minus minus+ minus +
It represents the effect of unmeasured anions on the plasma pH and is normally 10ndash18 mmollitre
2 CMicrovillus inclusion disease is a severe autosomal recessive enteropathy that is typically apparent within hours or days after birth It is the second most common cause of protracted diarrhoea in the newborn after infectious causes It is characterized by severe yellow watery diarrhoea and malabsorption due to hypoplasia andor atrophy of the villi of the small intestine secondary to an inherited defect in the brush border membrane This results in severe dehydration malnutrition and metabolic acidosis due to bicarbonate loss from the gut
3 CDiagnosis of microvillus inclusion disease is made on small bowel biopsy Electron microscopy findings are of intracellular brush border inclusions and densely packed apical cytoplasmic vesicular bodies indicating microvillous atrophy There is no cure Treatment is supportive with total parenteral nutrition and consideration of small bowel transplantation
Further reAding
Goulet O ruemmele f causes and management of intestinal failure
in children Gastroenterology 2006 130(suppl 1) s16ndash28
rhoads Jm Vogler rc lacey sr et al microvillus inclusion disease
In vitro jejunal electrolyte transport Gastroenterology 1991
100 811ndash817
Case 21 CGianottindashCrosti syndrome is a distinct self-limiting rash commonly associated with viral infections in children between 2 and 6 years of age It presents as multiple pink to redminusbrown papules or papulovesicles which may be pruritic and can become confluent Gianotti and Crosti initially described the exanthema as associated with hepatitis B virus and they termed it papular acrodermatitis of childhood It can occur in several viral diseases eg hepatitis A B and C coxsackie viruses and cytomegalovirus
2 BHepatitis is a syndrome characterized by inflammation or injury of liver cells which may develop into cell necrosis and subsequently fibrosis andor cirrhosis Biochemically there are raised liver enzymes The degree of transaminase elevation does not correlate with the severity of the disease process Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of viral hepatitis
3 DHepatitis B infection is transmitted via blood sexually or vertically Infection may be acute or chronic Diagnostic markers are the presence of surface antigen (HBsAg) and HBV DNA The presence of e antigen (HBeAg) indicates high infectivity Infected newborns have a 95 risk of becoming carriers this risk decreases with infection acquired later in childhood Approximately 15ndash25 of HBV carriers will die from cirrhosis or hepatocellular carcinoma Extrahepatic findings are more common in older children and include membranous glomerulonephritis and GianottiminusCrosti syndrome Fulminant hepatic failure occurs in severe cases resulting in persistent jaundice encephalopathy and coagulopathy Management includes counselling family members monitoring for ongoing liver disease and consideration of antiviral therapy
Further reAding
Brandt O abeck d Gianotti r Burgdorf W Gianotti crosti
syndrome J Am Acad Dermatol 2006 54 136ndash145
slowik mK Jhaveri r hepatitis B and c viruses in infants and
young children Semin Pediatr Infect Dis 2005 16 296ndash305
Case 31 CHypercalcaemia is uncommon in infancy The most common symptoms in this age group are irritability vomiting and constipation It may be a manifestation of Williams syndrome vitamin D or calcium excess as well as disorders associated with reduced bone formation such as hypophosphatasia or increased bone resorption such as malignancy Occasionally
Paediatrics and child health 184 205 copy 2008 elsevier ltd all rights reserved
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-
SympoSium neonatology
Dosage regimens for first- second- and third-line anticonvulsants in the neonatal period
Loading dose Second loading dose if first
unsuccessfulMaintenance dose
phenobarbitone 20 mgkg by slow iv injection 10 mgkg iv 25ndash5 mgkg od
phenytoin 20 mgkg iv over 20 min not recommended
midazolam 150ndash200 μgkg iv infusion 1 μgkgmin iv infusion increasing to 5 μgkgmin
until favourable response
lidocaine 2 mgkg iv over 10 min 6 mgkgh for 6 h iv then 4 mgkgh for 12 h then
2 mgkgh for 12 h
lorazepam 005ndash01 mgkg by slow iv injection
Diazepam 03ndash04 mgkg iv over 3ndash5 min
lidocaine should not be used if the infant has previously been treated with phenytoin
Table 3
seizure control was achieved with the adding of phenobarbitone in 62
Boylan et al14 assessed the efficacy of phenobarbitone (20ndash40 mgkg iv over 20 min) in 14 babies monitored by video-EEG in only four was there complete abolition of seizures and in the other 10 electroconvulsive seizure activity increased whereas clinical evidence of seizures reduced This has been termed elec-troclinical dissociation and anticonvulsant drug use in the new-born appears to increase this feature They also showed that the babies least likely to respond to the first-line AED are those with the most abnormal background EEG
Two studies have evaluated the use of phenobarbitone in babies who had sustained significant asphyxial insult at birth Hall et al13 compared high-dose phenobarbitone (mean 39 mgkg) versus standard dose (27 mgkg) and reported fewer convul-sions and a significant reduction of severe disability or death in the high dose group (RR 030 CI 010ndash093) A recent study from India16 of babies with hypoxicndashischaemic encephalopathy ran-domized 25 babies to phenobarbitone (20 mgkg loading dose) and compared them with 20 control babies Only 2 of 25 (4) in the phenobarbitone group developed convulsions compared with 8 of 20 (40) in the control group (p = 001) Because of the specific enrolment criteria (asphyxial insult) neither of these studies is strictly comparable to the studies by Painter et al15 and Boylan et al14 whose intention was to assess the efficacy of first-line anticonvulsant therapy on convulsions of any cause diagnosed either clinically or by EEG
Other anticonvulsants used as second- and third-line drugs have been subject to few studies in the newborn Midazolam is administered as a bolus followed by continuous infusion A recent study17 has shown that in 10 of 13 neonates given intravenous midazolam for status epilepticus control of electri-cal seizures was achieved within the first hour of treatment having been previously shown to be refractory to phenobarbi-tone treatment Some of these babies required a second bolus infusion of midazolam to obtain control of all electrographic seizures
In some parts of Europe lidocaine is used as a third-line anti-convulsant Malingre et al18 evaluated 20 infants refractory to
paeDiatRiCS anD CHilD HealtH 184 180
both phenobarbitone and midazolam and who were then given lidocaine by continuous infusion Lidocaine was effective in abolishing electroconvulsive seizures diagnosed by aEEG in 76 of the treatment courses studied No babies developed cardiac arrhythmias a previously reported complication of lidocaine in older patients As a result of pharmacokinetic studies the dosage regimen has been modified (see Table 3)
In summary phenobarbitone is effective in seizure control in less than 50 of babies and even when combined with phe-nytoin the efficacy of these drugs together remains poor More worrying is the observation that phenobarbitone tends to reduce clinically evident seizures thereby giving the clinician a false sense of security whilst having little or no effect on the num-bers of electroconvulsive disorders This has been summarized appropriately as lsquoafter all these years we still love what doesnrsquot workrsquo19 Both midazolam and lidocaine infusions appear to be effective in abolishing severe seizures in some infants resistant to phenobarbitone Lidocaine should not be given to babies previ-ously exposed to phenytoin for fear of a synergistic adverse effect on cardiac rhythm
Do antiepileptic drugs cause brain damageA riskndashbenefit analysis is needed to evaluate the efficacy of anticonvulsants in stopping neonatal seizures which is poor with standard anticonvulsants as discussed above against the risk of administering the anticonvulsant drugs themselves Phenobarbitone has been reported to have adverse effects on the developing brain including inhibition of brain growth20 neuronal toxicity21 and adverse behavioural and cognitive effects into adult life when administered to young animals22 Phenytoin shows unpredictable plasma levels and potential cardiotoxicity
Recent studies have shown an effect of AED exposure on the developing brain by causing neurodegeneration23 Phenytoin administration to immature rat pups at doses which produce serum levels similar to those achieved in human neonates was associated with widespread neuronal death as a result of apop-tosis (programmed cell death) Phenobarbitone had a similar effect when a dosage regimen similar to 40 mgkg was used and
copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
this effect was maximal in the more immature brain Diazepam and clonazepam also resulted in a similar effect Midazolam and lidocaine were not tested in this study The combination of phenobarbitone or phenytoin with diazepam had a particularly profound effect on neurodegeneration
In summary recent data suggest that the commonly used AEDs for neonatal convulsions may in themselves cause neuro-degeneration due to apoptosis with lasting effects on develop-ment Many babies with neonatal convulsions are treated with at least two AEDs and this may produce more severe adverse effects than the seizures themselves
Practical management of neonatal seizures
Assimilation of these data and formulation of a rational policy is difficult when faced with a fitting neonate on an intensive care unit and pressure on the medical staff to lsquodo somethingrsquo but it is important to accept that sometimes doing nothing is preferable to using potentially dangerous drugs in a situation which does not warrant such intervention Many babies who have normal interseizure neurological clinical findings and whose seizures are relatively brief and infrequent probably do not need anticon-vulsant medication A normal or near-normal background EEG trace should reassure the clinician that anticonvulsants can be withheld
Some causes of neonatal convulsions are treatable such as meningitis hypoglycaemia hypocalcaemia and inborn errors of metabolism and each baby should be rapidly and carefully investigated for cause of the convulsions
In some babies clinical assessment of seizures is difficult ie when the baby is very sick small or paralyzed Sometimes it may be difficult to assess the significance of certain movement pat-terns Under these circumstances an EEG may prove to be very helpful In many units EEG is not available out of hours and a simple aEEG or CFM is strongly advised Modern instruments are very simple to apply and prolonged or frequent seizures should be identified with only moderate training The printout can be faxed to a more senior doctor if there is doubt as to what is shown on the trace
The balance of knowledge now is that frequent seizures cause additional damage to the developing brain and that treatment to abolish the seizures is warranted Unfortunately there is little evidence that the majority of seizures can be effectively termi-nated by current standard therapy Furthermore it appears that the more abnormal the background EEG the more difficult it is to control the seizures Nevertheless a written protocol for the management of neonatal convulsions is required on each unit Phenobarbitone and phenytoin remain the mainstay of treat-ment although their effectiveness is disappointing There is little to suggest that midazolam is more effective than lidocaine as third-line therapy but lidocaine is precluded if phenytoin has been previously used
In view of the anxiety as to the neurodegenerative effects on the immature brain of most anticonvulsants used in the neonatal period (particularly when multiple drugs are used) it is prefer-able to use only one drug to maximum dosage before introduc-ing a second In addition the duration of anticonvulsants should be minimized and the drugs stopped at the earliest opportu-nity It is my practice to stop anticonvulsants prior to discharge
paeDiatRiCS anD CHilD HealtH 184 18
from hospital if the baby is neurologically normal on clinical examination
REFEREnCES
1 Ronen gm penney S andrews W the epidemiology of clinical
neonatal seizures in newfoundland a population-based study
J Pediatr 1999 134 71ndash75
2 lanska mJ lanska DJ Baumann RJ et al a population-based study
of neonatal seizures in Fayette County Kentucky Neurology 1995
45 724ndash732
3 Rennie Jm Chorley g Boylan gB et al non-expert use of the
cerebral function monitor for neonatal seizure detection Arch Dis
Child Fetal Neonatal Ed 2004 89 F37ndashF40
4 tekgul H gauvreau K Soul J et al the current etoliologic profile
and neurodevelopmental outcome of seizures in term newborn
infants Pediatrics 2006 117 1270ndash1280
5 Surtees R Wolf n treatable neonatal epilepsy Arch Dis Child 2007
92 659ndash661
6 Ben-ari y Holmes gl effects of seizures on developmental
processes in the immature brain Lancet Neurol 2006 5 1055ndash
1063
7 Holmes gl gairsa Jl Chevassus-au-louis n et al Consequences of
neonatal seizures in the rat morphological and behavioral effects
Ann Neurol 1998 44 845ndash857
8 Stafstrom Ce Chronopoulos a thurber S et al age-dependent
cognitive and behavioural deficits following kainic-acid inducing
seizures Epilepsia 1993 34 420ndash432
9 Schmid R tandon p Stafstrom Ce et al effects of neonatal seizures
on subsequent seizure-induced brain injury Neurology 1999 53
1754ndash1761
10 Hoffmann aF Zhao Q Holmes gl Cognitive impairment following
status epilepticus and recurrent seizures during early development
support for the ldquotwo-hit hypothesisrdquo Epilepsy Behav 2004 5
873ndash877
11 Wirrell eC armstrong ea osman lD et al prolonged seizures
exacerbate perinatal hypoxic-ischemic brain damage Pediatr Res
2001 50 445ndash454
12 Carmo KB Barr p Drug treatment of neonatal seizures by
neonatologists and paediatric neurologists J Paediatr Child Health
2005 41 313ndash316
13 Hall Rt Hall FK Daily DK High-dose phenobarbital therapy in term
newborn infants with severe perinatal asphyxia a randomized
prospective study with three-year follow-up J Pediatr 1998 132
345ndash348
14 Boylan gB Rennie Jm pressler Rm et al phenobarbitone neonatal
seizures and video-eeg Arch Dis Child Fetal Neonatal Ed 2002 86
F165ndash170
15 painter mJ Scher mS Stein aD et al phenobarbital compared with
phenytoin for the treatment of neonatal seizures N Engl J Med
1999 341 485ndash489
16 Singh D Kumar p narang a a randomized controlled trial of
phenobarbital in neonates with hypoxic ischemic encephalopathy
J Matern Fetal Neonatal Med 2005 18 391ndash395
17 Castro Conde JR Borges H Domenech martinez e et al midazolam
in neonatal seizures with no response to phenobarbital Neurology
2005 64 876ndash879
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
18 malingre mm Van Rooij lgm Rademaker Cma et al Development
of an optimal lidocaine infusion strategy for neonatal seizures Eur
J Pediatr 2006 165 598ndash604
19 Sankar R painter mJ neonatal seizures after all these years we still
love what doesnrsquot work Neurology 2005 64 776ndash777
20 Diaz J Schain J Bailey Bg phenobarbital-induced brain growth
retardation in artificially reared rat pups Biol Neonate 1977 32 77ndash82
21 mattson RH phenobarbital toxicity in levy RH Dreifuss Fe
mattson RH et al eds antiepipeptic Drugs 3rd edn new york
Raven 1985 p 341ndash355
22 mikati ma Holmes gl Chronopoulos a et al phenobarbital
modifies seizure-related brain injury in the developing brain Ann
Neurol 1994 36 425ndash453
23 Bittigau p Sifringer m genz K et al antiepileptic drugs and
apoptotic neurodegeneration in the developing brain Proc Natl
Acad Sci U S A 2002 99 15089ndash15094
paeDiatRiCS anD CHilD HealtH 184 182
Practice points
bull the clinician needs to be aware that almost any repetitive
stereotype movement pattern can be a manifestation of
neonatal seizures
bull eeg is important in defining neonatal seizures
bull Frequent short-lived seizures have been shown to cause long-
term neurodevelopmental problems
bull Conventional anticonvulsant medication is ineffective in
abolishing neonatal seizures in greater than 50 of cases
bull there is evidence that exposure of the neonatal brain to
multiple anticonvulsants causes neuronal death
bull Future research is needed to evaluate more effective
anticonvulsants for treating this condition
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
Emotional support for families of sick neonatesMarina nicolaou
cristine Glazebrook
AbstractParents of sick neonates experience high levels of stress anxiety and
depression Most interventions with families of sick infants have focused
on fostering the motherndashinfant relationship through the provision of
information about infant developmental needs or through increased
motherndashinfant contact Many of these studies have reported improved
maternal well-being though there are some concerns about the scope
and practicality of large-scale interventions The few studies to have
prioritized emotional support for parents of sick neonates have pro-
duced encouraging results even interventions requiring relatively few re-
sources such as telephone support parent-to-parent support and group
support have been associated with reduced psychological morbidity for
parents The needs of parents can change throughout their infantrsquos hos-
pitalization and not all want or benefit from the provision of additional
support Thus neonatal intensive care units should aim to provide a
varied flexible and sustainable programme of support options Further
research should focus on the needs of fathers
Keywords mental health neonatal intensive care parents
The admission of an infant to neonatal care is acknowledged to be a source of considerable distress for families This review aims to explore evidence for the psychological impact on families of having an infant in neonatal intensive care and to identify evi-dence for the effectiveness of interventions to promote parental well-being It will conclude with recommendations for strategies to support parents of vulnerable infants and suggestions for fur-ther research
Psychological impact of neonatal care for parents
The majority of research examining the effect on parents of having a sick neonate has focused on families of premature or low birthweight infants Such research has found that parents with a sick neonate exhibit high levels of stress compared to normative samples and to parents of healthy full-term infants1 Singer et al2 examined the stress experienced by mothers of high-risk very low birthweight (VLBW) low-risk VLBW and term
Marina Nicolaou MPhil is a Teaching Assistant at the School of
Community Health Sciences University of Nottingham Nottingham UK
Cristine Glazebrook PhD is a Professor of Health Psychology at the School
of Community Health Sciences University of Nottingham Nottingham UK
PaeDiaTrics anD cHilD HealTH 184 196
infants Several self-report measures were used including the Brief Symptom Inventory the Parenting Stress Index (PSI) the Impact on Family Scale and the Family Inventory of Life Events and Changes (FILE) Mothers of VLBW infants had more psycho-logical distress at 1 month compared to mothers of term infants Mothers of high-risk VLBW infants also reported high psycho-logical distress at 2 years and high levels of parenting stress at 3 years Mothers have also been found to have higher stress levels compared to fathers Shaw et al3 examined the prevalence of acute stress disorder (ASD) in 40 parents whose infants were in the neonatal intensive care unit (NICU) Nearly half of the moth-ers (44) met the criteria for ASD although none of the fathers did Furthermore the severity of the symptoms (measured by the number of concurrent symptoms) was greater for the moth-ers than for the fathers3 The reasons behind this difference have been widely speculated with some believing that it is due to the mothersrsquo greater psychological involvement with the infant as evidenced by their general greater vulnerability to postpartum psychological disorder It could also reflect gender differences in coping style
Having an infant who requires intensive medical care repre-sents a significant emotional burden for families Not only is there extreme anxiety surrounding the infantrsquos health and distress for the childrsquos suffering there is also the unfamiliar and intimidating environment of the NICU to adjust to Hopper in her review of the literature identified sources of stress for parents of sick neo-nates as falling into three areas4 Situational factors included the severity of the infantrsquos illness and how parents adapted to the life crisis of having a sick infant Personal factors involved parental emotions about their roles and the instrumental and informa-tional support which were available to them The third area was classified as environmental sources of stress and included the environment of the NICU and the relationship between parents and members of staff This relationship has been examined by several studies in the nursing literature nurses are seen as ide-ally placed to provide the necessary support and information to parents with sick neonates However whilst some studies have shown that supportive and helpful hospital staff can have a posi-tive effect on parents other studies have highlighted the prob-lems and difficulties which can manifest It has been shown that parents and nurses often have very different ideas about issues eg the necessary skills and competencies needed in an NICU or the characteristics that make a lsquogood motherrsquo
Research has shown that there may be a relationship between high levels of parental stress and an increased likelihood of depression5 Postpartum depression is a psychiatric illness which appears in 10ndash15 of postpartum women Its reported preva-lence rates however have ranged from less than 10 up to 306 depending on the instruments used the population exam-ined and the timing of the research Several factors have been found to be associated with postpartum depression including poor social support and infant-related stressors6 Evidence indi-cates that postnatal depression may be underreported and this is of concern since the mental and psychological health of the mother can affect her relationship with her infant and thus the infantrsquos cognitive and emotional development5 Depressed moth-ers appear to look touch and talk to their infants less frequently and also appear to show fewer positive and more negative faces7 The vocalizations of mothers suffering with depression have also
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
been found to be less effective at promoting cognitive growth and learning in infants8
If researchers are interested in finding ways of providing sup-port for families of sick neonates then they must listen to what such families perceive their needs to be in order to avoid increas-ing anxiety and distress Furthermore the provision of appropri-ate support be it emotional informational or social will enhance parental coping abilities increase self-esteem and reduce anxiety It should be noted though that the research conducted around these issues has often taken lsquosupport needsrsquo as being synony-mous with lsquoinformation needsrsquo Such studies have examined the type the amount and quality of information that parents receive and perceive themselves as needing but have not explored in equal depth the perceived emotional support needs of families who have a sick infant In addition the needs of parents may change throughout their infantrsquos illness Ward examined the per-ceived needs of 52 parents of infants in an NICU9 Parents rated the needs of their hospitalized infant as most important along with the need to be reassured Interestingly they ranked their support needs as least important This research was conducted during the first week of the infantsrsquo hospitalization however which would explain the preoccupation of the parents with the infantrsquos health These results demonstrate that if researchers want to find ways of providing emotional support to parents of sick neonates they must be prepared not only to listen to parents but also to be flexible enough to satisfy the parentsrsquo changing needs and expectations
Interventions aimed at supporting parents
Most interventions that been evaluated in controlled studies have focused on supporting the motherndashinfant relationship and provid-ing information on infant development Many of these interven-tions have included the aim of improving the parental emotional state and thus psychological outcomes such as stress or anxi-ety have been assessed However few studies appear to include fathers This means that strategies implemented to provide emo-tional support to families of sick neonates are often derived from interventions tailored for mothers even though fathers may have different emotional needs
A wide range of interventions with mothers and infants has been evaluated in the NICU Increasing motherndashinfant contact through kangaroo care has been found to reduce maternal anxiety1011 and educational programmes delivered to fami-lies in the NICU have also been associated with reduced emo-tional difficulties in parents12ndash14 Kaaresen and colleagues implemented an intervention which consisted of eight sessions before discharge and four home visits all by trained nurses The sample included 71 premature infants in the intervention group 69 premature infants in the control group and 74 infants in the full-term control group The randomized controlled trial found that the intervention reduced parenting stress in both mothers and fathers of premature infants compared to controls to a level equivalent to parents in the term control group13 At 6 months corrected age mothers of preterm infants who had not received the intervention had total PSI scores which were 17 points higher than the mothers of infants born at term (an effect size of 057) A similar study evaluated the efficacy of an educationalndashbehavioural programmendashCreating Opportunities for
PaeDiaTrics anD cHilD HealTH 184 19
Parent Empowerment (COPE) ndash through a randomized controlled trial with 260 families of premature infants14 COPE was a four-phase educationalndashbehavioural programme which began as early as 2ndash4 d after mothers had given birth and continued until 1 week after discharge from the NICU The programme consisted of audiotaped and written infant behaviour information along with photographs which focused on common behaviours and characteristics of premature infants It also included various par-ent activities in the form of a four-phase workbook which aimed to assist mothers in the implementation of the experimental infor-mation COPE was found significantly to reduce maternal stress in the NICU as well as maternal anxiety and depressive symptoms after hospitalization In contrast a cluster randomized trial of a parenting intervention delivered to mothers of very premature infants from soon after birth showed no benefits for parenting stress1 The authors hypothesized that the intervention had not been of sufficient intensity particularly in the weeks surrounding discharge Neonatal care presents a significant barrier to parent-ing in the early weeks following a very preterm birth and so inter-ventions which focus on the developmental needs of infants and the parentndashchild relationship should particularly aim to support parents as they take on the parenting role There was also concern that the intervention had failed to reach those most at risk
Since large-scale projects can be costly to implement and may often fail to reach the families in most need it may be wiser to focus on intervention programmes which are more practical and easier to implement within a neonatal care setting Research has shown that even interventions which are based on one-off meet-ings with parents of sick neonates can be effective Jotzo and Poets examined the effect of an intervention programme aimed at reducing the severity of traumatic responses as a result of giv-ing birth prematurely15 Their programme consisted of a one-off intervention meeting along with additional psychological help throughout the hospitalization of the infant The meeting cov-ered a variety of issues including a reconstruction of the events shortly before and after the infantrsquos birth relaxation techniques discussion of coping strategies available resources and social support and support during emotional outbursts The measures used included the Impact of Event Scale (IES) and the Peritrau-matic Dissociative Experience Questionnaire At discharge the mothers who received the intervention were found to have a significantly lower traumatic impact as a result of premature birth Furthermore fewer mothers in the intervention group showed symptoms of clinically significant psychological trauma at discharge compared to mothers in the control group (36 vs 76)15 The lsquoParents Circle Programrsquo is another intervention with a similar structure16 This consisted of a 90 min session for parents with the aim of enhancing the developing relationship between parents and infants and to offer parents support A total of 104 parents (59 mothers and 45 fathers) and 44 members of hospital staff were asked to evaluate the programme and their results were analysed using content analysis Families reported gaining perspective on their situation feeling supported becom-ing aware of cues and optimizing interactions and becoming aware of available resources Parents and staff alike felt that participating in the intervention helped parents overcome the difficulties associated with the early time of their infantrsquos hos-pitalization Additional studies have also found positive results with fairly minimal interventions including discussion groups
7 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
in the NICU music during kangaroo care and pairing mothers of sick neonates with trained mothers who had been through similar experiences
Parent support programmes
Parent support programmes (PSPs) which are based in NICUs can provide parents with the opportunity to talk to parents who have been in similar situations and also to discuss their emo-tions with professionals who can help them cope with their situa-tion111718 The parent-to-parent support programme for mothers of preterm infants evaluated by Preyde and Ardal included edu-cational parental support group meetings and individual par-ent-to-parent support (primarily telephone support)19 Measures used included the Parental Stressor Scale NICU the State and the Trait Anxiety Inventories and the Beck Depression Inven-tory After 4 months of participation mothers in the intervention group reported lower levels of stress state anxiety and depres-sion compared to control group mothers The authors speculated however that the participants who were able to meet face to face with other parents were those who benefited the most Hurst conducted a comprehensive survey of an NICU-based PSP This PSP was provided in a variety of formats including a weekly parent support group hospital visitation and 24-h telephone sup-port20 Of the 477 participants 303 families used the PSP dur-ing a 2-year evaluation period with 78 using only one form of support and 18 using two forms Of a sub-sample of 48 parents asked to complete an evaluation of the PSP 92 stated that they would recommend such a programme to other parents Furthermore the majority of parents felt that it made them feel supported and helped them deal with their emotions20 This is an indication that such programmes can be very successful in sup-porting parents throughout their infantrsquos hospitalization It also shows that it can be beneficial to give parents several options and formats when it comes to such support services It is impor-tant to consider though that both the Hurst and the Preyde and Ardal studies found that some participants did not find the sup-port programmes helpful even reporting that they had caused them increased stress and anxiety Therefore it should not be assumed that support programmes will suit every individual and will provide the required support for all parents1920 NICUs need to be flexible enough to provide parents with a range of forms of support to choose from
The increased understanding of the strains that parents of sick neonates have to deal with has also led to efforts to improve customary practices in NICUs Family-centred care focuses on infants and their needs and attempts to redefine the relationship between parents and caregivers These practices strive to provide parents with support during their infantrsquos illness by focusing on freely sharing information and on the collaboration between parents and hospital staff Family-centred care has been found to be associated with several beneficial outcomes including improved parental satisfaction increased parental comfort staff satisfaction and decreased parental stress18 Research is already examining these practices and questioning how these can be improved further Such research reflects the increasing effort focused on lsquohumanizingrsquo the environment in NICUs in order to make parents feel more comfortable about spending time with their infants
PaeDiaTrics anD cHilD HealTH 184 19
Conclusion
Surprisingly few interventions have prioritized the provision of emotional support for parents of sick neonates or accounted for the changing needs and wishes of parents over the course of their infantrsquos care Large-scale supportive education-based inter-ventions have been shown to be effective in reducing parental distress However the feasibility and sustainability of such pro-grammes should also be considered Programmes which require significant additional resources can be expensive and there are also issues of training and quality control Interventions which require significant input from parents may also place additional burdens on families making them potentially less accessible to those most at risk Arguably the aim should be to explore ways of providing acceptable and effective informational support which could be complemented by emotional support from health professionals and from other parents in the unit Increasingly studies are exploring the use of computers and multimedia as an engaging flexible and cost-effective method of targeting indi-vidual needs and providing support and information Such com-puter-based and interactive multimedia interventions have been found to be successful with a range of patient groups and could therefore be examined as a complementary method of providing informational support to families with sick neonates
REfEREnCEs
1 Glazebrook c Marlow n israel c et al randomised trial of a
parenting intervention during neonatal intensive care Arch Dis Child
Fetal Neonatal Ed 2007 92 F438ndash443
2 singer lT salvator a Guo s collin M lilien l Baley J Maternal
psychological distress and parenting stress after the birth of a very
low-birth-weight infant JAMA 1999 281 799ndash805
3 shaw rJ Deblois T ikuta l Ginzburg K Fleisher B Koopman c
acute stress disorder among parents of infants in the neonatal
intensive care nursery Psychosomatics 2006 47 206ndash212
4 Hopper a sources of stress for parents of a sick neonate a
literature review Pediatr Nurs 2000 30 29ndash32
5 Davis l edwards H Mohay H wollin J The impact of very
premature birth on the psychological health of mothers Early Hum
Dev 2003 73 61ndash70
6 Bernazzani O saucier J-F David H Borgeat F Psychosocial
predictors of depressive symptomatology level in postpartum
women J Affect Disord 1997 46 39ndash49
7 Field T infants of depressed mothers Infant Behav Dev 1995 18
1ndash13
8 Kaplan Ps Bachorowski J-a Zarlengo-strouse P child-directed
speech produced by mothers with symptoms of depression fails
to promote associative learning in 4-month-old infants Child Dev
1999 70 560ndash570
9 ward K Perceived needs of parents of critically ill infants in
a neonatal intensive care unit (nicU) Pediatr Nurs 2001 27
281ndash286
10 lai Hl chen cJ Peng Tc et al randomized controlled trial of music
during kangaroo care on maternal state anxiety and preterm infantsrsquo
responses Int J Nurs Stud 2006 43 139ndash146
8 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
11 Tallandini Ma scalembra c Kangaroo mother care and mother-
premature infant dyadic interaction Infant Ment Health J 2006 27
251ndash275
12 Ohgi s Fukuda M akiyama T Gima H effect of an early intervention
programme on low birthweight infants with cerebral injuries
J Paediatr Child Health 2004 40 689ndash695
13 Kaaresen Pi ronning Ja Ulvund se Dahl lB a randomized
controlled trial of the effectiveness of an early-intervention program
in reducing parenting stress after preterm birth Pediatrics 2006
118 e9ndash19
14 Melnyk BM Feinstein nF alpert-Gillis l et al reducing premature
infantsrsquo length of stay and improving parentsrsquo mental health
outcomes with the creating opportunities for parent empowerment
(cOPe) neonatal intensive care unit program a randomized
controlled trial Pediatrics 2006 118 e1414ndash1427
15 Jotzo M Poets cF Helping parents cope with the trauma of
premature birth an evaluation of a trauma-preventive psychological
intervention Pediatrics 2005 115 915ndash919
16 Pearson J andersen K evaluation of a program to promote positive
parenting in the neonatal intensive care unit Neonatal Netw 2001
20 43ndash48
17 roman l lindsay J Boger r et al Parent-to-parent support
initiated in the neonatal intensive care unit Res Nurs Health 1995
18 385ndash394
18 Meyer ec coll cTG lester BM Boukydis cFZ McDonough sM Oh w
Family-based intervention improves maternal psychological well-
being and feeding interaction of preterm infants Pediatrics 1994
93 241ndash246
PaeDiaTrics anD cHilD HealTH 184 19
19 Preyde M ardal F effectiveness of a parent ldquobuddyrdquo program for
mothers of very preterm infants in a neonatal intensive care unit
CMAJ 2003 168 969ndash973
20 Hurst i One size does not fit all Parentsrsquo evaluations of a support
program in a newborn intensive care nursery J Perinat Neonatal
Nurs 2006 20 252ndash261
Practice points
bull Parents of sick neonates experience significant distress and
exhibit higher levels of stress anxiety and depression than
parents of healthy infants
bull educational support emotional support and increased
motherndashinfant contact have been shown to promote maternal
well-being
bull emotional support for fathers has been largely neglected in
the research literature
bull Parents benefit from a choice of supportive facilities which
could include face-to-face sessions with health professionals
telephone support hospital visitation parent-to-parent
support and unit-based group support meetings
bull Parentsrsquo support needs can change during their infantrsquos
hospitalization and not all parents want or benefit from the
provision of additional information and emotional support in
the neonatal unit
9 copy 2008 elsevier ltd all rights reserved
Personal Practice
When should enteral feeds be started in preterm infantsnicholas D embleton
AbstractPaediatricians are regularly faced with the question of when best to start
enteral feeds in preterm infants this is important as longer term out-
come may be compromised by sub-optimal nutrition in early life clinical
factors that may affect the decision to start and the risk and benefits
are discussed
Keywords breast milk feeding nutrition parenteral nutrition
Key points in the history
Alice is lsquonutritionally vulnerablersquo and whilst this may not be immediately apparent it will affect her long term outcome Her energy stores are extremely limited and consist primarily of pro-tein She has less than 5 fat and little energy associated with stored glycogen She is losing about 1 gkgd protein equivalent so she needs at least that and a minimum of 50ndash60 kcalkg of energy just to maintain the status quo let alone grow
Her weight is on the 25th centile Review of any antenatal his-tory may reveal whether fetal growth was normal Fetal growth retardation can occur with a weight greater than 10th centile The presence of antenatal absent or reversed end diastolic flow in the umbilical artery indicates poor gut blood flow This increases the risk of necrotizing enterocolitis (NEC) and might suggest a more cautious approach to starting feeds1
She has no important cardiovascular problems but if she were hypotensive gut blood flow may be low There is no umbilical
Nicholas D Embleton BSC (Hons) MBBS (Hons) MD FRCPCH is Consultant in
Neonatal Medicine at Newcastle Neonatal Service Royal Victoria
Infirmary Newcastle upon Tyne NE1 4LP UK
Should you start feeds at a day of age
alice was born following spontaneous labour at 30 weeksrsquo
gestation she weighed 1300 g and is now 18 h old she was
briefly ventilated and then extubated to continuous positive
airway pressure 12 h ago in 35 oxygen she has had caffeine
citrate but still has intermittent episodes of self-correcting
apnoea she was commenced on iv 10 dextrose but this was
replaced by a parenteral amino acid solution (referred to as
lsquotPnrsquo) along with intralipid at 0900 this morning serum glucose
is 11 mmoll and blood pressure is 42 systolic
PaeDiatrics anD cHilD HealtH 184 20
arterial catheter in situ but there is no good evidence that this should delay the decision to start feeds Her glucose is high but this is quite common in a baby like this Could this be a sign of sepsis Caffeine does not affect the incidence of NEC2 The great-est risk factor for NEC in this case is prematurity
What else might be found on examination
Up until 24 h ago she was swallowing large amounts of amniotic fluid What will have changed since then
General examination should confirm peripheral perfusion lsquogestaltrsquo view (does she look lsquowellrsquo) and cardiovascular status lsquoBowel soundsrsquo are not usually helpful
The most important variable likely to affect gut perfusion is the arterial duct Precordial lsquoheaversquo and a loud murmur are sug-gestive but it is possible to have a significant ductal shunt in a baby with a normal examination Cardiac ultrasound will con-firm this diagnosis It might be better to treat a large shunt first with indometacin and to delay starting feeds for a further 24 h
It is not possible to assess gut perfusion clinically but normal perfusion elsewhere (adequate urine output usually indicates adequate renal perfusion) would be reassuring Most preterm babies have a few abdominal lsquoloopsrsquo visible but a distended abdomen with many palpable loops suggests ileus This might be secondary to sepsis or poor gut blood flow Preterm babies do not pass much meconium in the first 24ndash48 h
Balance of risks between starting and withholding feeds
Alice requires 35ndash4 gkgd of protein and 120 kcalkgd to grow3 This will initially be provided parenterally Delaying feeds increases the risk of gut villous atrophy and prolongs the need for lsquototal parenteral nutrition (TPN)rsquo TPN requires intravenous access and so increases the risk of sepsis and when prolonged use is required combined with the lack of enteral feeding may result in hepatic impairment
Delaying feeds may allow a gut that has been chronically under-perfused to re-establish more normal perfusion although normal gut endocrine function digestive enzyme upregulation and motility require a source of intraluminal nutrients1 A recent study suggested benefit from delaying the introduction of feeds4 but methodologi-cal problems exist5 Although a Cochrane meta-analysis suggested no benefit only two studies were included6 A large UK-based trial is examining the effect of early or late feeding in preterm infants who were born growth retarded following identification of antena-tal absent or reversed end diastolic flow in the umbilical artery7
When starting feeds what volume should be used
There are no good data to guide this decision We start with 24 mlkg (1 mlkgh) and then increase by this amount each day Most babies achieve full enteral feeds (ge150 mlkgd) by a week of age Feeding guidelines improve the outcome8 Measure-ment or assessment of gastric aspirates is not consistently useful in predicting subsequent feeding intolerance or development of NEC Aspirate volumes equivalent to or sometimes greater than the amount given in the preceding 1ndash2 h are usually normal Most aspirates have a greenish colour Thick bloody or intensely bile-stained aspirates require detailed assessment
0 copy 2008 elsevier ltd all rights reserved
Personal Practice
What else affects decisions and outcome
Feeding success is affected by sepsis and NEC Scrupulous atten-tion should be paid to hand washing and intravenous access and blood sampling should be minimized There is no good evidence to support the routine use of pro-kinetic agents or H2 blockers
The most important clinical intervention affecting the occur-rence of NEC is the use of breast milk9 All efforts should be directed at persuading parents of the benefits and supporting the process Some clinicians delay starting feeds for a further 24 h whilst expressed breast milk becomes available Donor breast milk might be equally efficacious10
RefeRenceS
1 Dorling J Kempley s leaf a Feeding growth restricted preterm
infants with abnormal antenatal Doppler results Arch Dis Child Fetal
Neonatal Ed 2005 90 F359ndash363
2 schmidt B roberts rs Davis P et al caffeine therapy for apnea of
prematurity N Engl J Med 2006 354 2112ndash2121
PaeDiatrics anD cHilD HealtH 184 20
3 embleton nD Pang n cooke rJ Postnatal malnutrition and growth
retardation an inevitable consequence of current recommendations
in preterm infants Pediatrics 2001 107 270ndash273
4 Berseth cl Bisquera Ja Paje VU Prolonging small feeding volumes
early in life decreases the incidence of necrotizing enterocolitis in
very low birth weight infants Pediatrics 2003 111 529ndash534
5 Menon G Boyle eM embleton nD et al introduction of enteral
feeds in preterm infants Pediatrics 2004 114 327ndash328
6 Kennedy Ka tyson Je chamnanvanikij s early versus delayed
initiation of progressive enteral feedings for parenterally fed low
birth weight or preterm infants Cochrane Database Syst Rev 2000
cD001970
7 wwwnpeuoxacukadept
8 Patole sK de Klerk n impact of standardised feeding regimens on
incidence of neonatal necrotising enterocolitis a systematic review
and meta-analysis of observational studies Arch Dis Child Fetal
Neonatal Ed 2005 90 F147ndash151
9 lucas a cole tJ Breast milk and neonatal necrotising enterocolitis
Lancet 1990 336 1519ndash1523
10 Boyd ca Quigley Ma Brocklehurst P Donor breast milk versus
infant formula for preterm infants systematic review and meta-
analysis Arch Dis Child Fetal Neonatal Ed 2007 92 F169ndash175
1 copy 2008 elsevier ltd all rights reserved
self-assessment
Case 1A term male infant born to consanguineous parents is assessed at 24 h of age due to poor feeding profuse yellow watery diar-rhoea and irritability He weighed 32 kg at birth and delivery was uneventful There was no polyhydramnios He has been breastfed since birth On examination he is pale with a non-tender but distended abdomen and reduced bowel sounds His weight is 275 kg and he looks dehydrated Examination is otherwise normal
Initial investigations (normal values in parentheses) showed
sodium 149 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 65 mmollitre (25ndash75)
creatinine 147 μmollitre (40ndash110)
chloride 119 mmollitre (95ndash105)
haemoglobin 172 gdl (140ndash200)
White blood cell count 80 times 109litre (100ndash260)
Platelet count 302 times 109litre (150ndash400)
arterial blood gas
ph 720 (730ndash745)
PcO2 23 kPa (46ndash60)
Bicarbonate 68 mmollitre (220ndash260)
Base excess minus186 mmollitre (minus20 to +20)
lactate 59 mmollitre (06ndash24)
An abdominal X-ray shows distended bowel loops with no intramural thickening or pneumoperitoneum (Figure 1)
He was given nil by mouth and received intravenous fluids and antibiotics His dehydration improved but the metabolic acidosis and diarrhoea persisted despite receiving no enteral feeds and the commencement of total parenteral nutrition Blood and stool cultures were negative
1 Which of the following best describes these results Choose ONE answer ONLY from the followingA Hypernatraemia hyperchloraemic metabolic acidosis
with increased anion gapB Hypernatraemia hyperchloraemic metabolic acidosis
with normal anion gap
Manish Sadarangani BM BCh MA MRCPCH is Clinical Research Fellow
at the Department of Paediatrics University of Oxford Centre for
Clinical Vaccinology and Tropical Medicine Churchill Hospital
Oxford OX3 7LJ UK
Shabna Rajapaksa MB BChir MA MRCPCH is Specialist Registrar in
Paediatrics at the Paediatric Intensive Care Unit John Radcliffe
Hospital Oxford OX3 9DU UK
Nicholas Mann MD FRCP FRCPCH DCH is Consultant Paediatrician at the
Department of Paediatrics Royal Berkshire Hospital Reading RG1
5AN UK
self-assessment
C Hypernatraemic dehydration and compensated metabolic acidosis
D Acute renal failureE Renal tubular acidosis
2 What is the likely diagnosis Choose ONE answer ONLY from the followingA Hirschsprung disease ndash long segmentB Cystic fibrosis with meconium ileusC Microvillus inclusion diseaseD Cowrsquos milk protein intoleranceE Lactose intolerance
3 What is the investigation of choice Choose ONE answer ONLY from the followingA Rectal biopsy with staining for acetylcholine receptorsB Immunoreactive trypsinC Gastrointestinal endoscopy and biopsyD Stool microscopy and cultureE Stool reducing substances
Case 2A 4-year-old boy presents with a 3 d history of jaundice and a florid rash He has had orange urine and there is no change in his stool colour His family originate from Kosovo and have lived in the UK for the last 8 years He has never left the UK There is no history of blood transfusion or sex-ual abuse The grandmother was recently diagnosed with hepatitis B
On examination he is well apyrexial and mildly jaundiced with cervical and axillary lymphadenopathy He has an exten-sive papular rash over the face extremities and trunk (Figure 2) There is 3 cm hepatomegaly with no splenomegaly or ascites Examination is otherwise normal
Figure 1 abdominal X-ray of baby
Paediatrics and child health 184 202 copy 2008 elsevier ltd all rights reserved
self-assessment
Initial investigations are as follows
haemoglobin 110 gdl (113ndash135)
White blood cell count 108 times 109litre (50ndash150)
Platelet count 278 times 109litre (150ndash400)
inr 10 (08ndash12)
aPt ratio 10 (08ndash13)
sodium 140 mmollitre (135ndash145)
Potassium 42 mmollitre (35ndash50)
Urea 56 mmollitre (25ndash75)
creatinine 65 μmollitre (45ndash120)
total bilirubin 66 μmollitre (0ndash15)
conjugated bilirubin 23 μmollitre (0ndash10)
alanine aminotransferase (alt) 2033 iUlitre (0ndash35)
alkaline phosphatase 987 iUlitre (71ndash234)
Gamma-glutamyl transferase (GGt) 870 iUlitre (0ndash51)
1 What is the name of this rash Choose ONE answer ONLY from the followingA Erythema multiformeB Erythema migransC GianottiminusCrosti syndromeD EczemaE Dermatitis herpetiformis
2 What is the most likely diagnosis Choose ONE Answer ONLY from the followingA Autoimmune hepatitisB Hepatitis BC Hepatitis DD Wilson diseaseE Alpha-1 antitrypsin deficiency
3 What is the best means of management Choose ONE answer ONLY from the followingA Isolation until the jaundice disappearsB ImmunosuppressionC Copper chelating agents and genetic counsellingD Patient and family education with consideration of
antiviral agentsE Liver transplantation
Case 3A 10-month-old boy presents with 3 weeks of vomiting and constipation ndash he is passing hard stools every 2ndash3 days He has fallen from the 9th to below the 04th centile in the last 6 weeks He passed meconium within the first 24 h of life On examina-tion he looks pale and there are some dysmorphic features ndash a short nose long philtrum and wide mouth He has normal heart sounds with a grade 3 ejection systolic murmur loudest at the upper right sternal edge Examination is otherwise normal
Initial investigations are as follows
haemoglobin 91 gdl (113ndash141)
total white blood cell count 124 times 109litre (60ndash170)
Platelet count 407 times 109litre (150ndash400)
sodium 144 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 78 mmollitre (25ndash75)
creatinine 78 μmollitre (45ndash120)
albumin 52 glitre (35ndash50)
corrected calcium 384 mmollitre (238ndash263)
Phosphate 167 mmollitre (099ndash157)
1 What is the most likely diagnosis Choose ONE answer ONLY from the followingA HyperparathyroidismB Acute leukaemiaC Williams syndromeD Hypervitaminosis DE Familial hypocalciuric hypercalcaemia
2 Which investigation would be most useful in establishing the diagnosis Choose ONE answer ONLY from the followingA Intact parathyroid hormone assayB Blood filmC Fluorescent in-situ hybridization for 7q1123 deletionD 25-hydroxyvitamin D assayE Urine calciumcreatinine ratio
3 Which of the following treatments would not be suitable for this patient Choose ONE answer ONLY from the followingA Low calcium dietB Normal saline infusionC FurosemideD CorticosteroidsE Bisphosphonates
Case 4A 10-week-old girl presents with a 2-day history of poor feed-ing Her mother has been concerned about weakness since birth She only has a flicker of movement in the arms none in the legs and has a weak cry She has been passing urine and opening her bowels normally She was born at full term by normal delivery and did not require any resuscitation at birth Normal fetal movements were felt antenatally and there was no polyhydramnios She is the first child of non- consanguineous parents and there is no significant family his-tory On examination she is alert and fixing and following appropriately She has a weak cry and a weak suck There is reduced central and peripheral tone with marked head lag
Figure 2 rash found on examination
Paediatrics and child health 184 203 copy 2008 elsevier ltd all rights reserved
self-assessment
Muscle power is grade 3 out of 5 in the arms and legs There is no muscle or tongue fasciculation and she has absent reflexes throughout The remainder of the examination is normal
Electromyogram shows irregular polyphasic motor unit potentials with marked instability consistent with a dener-vating and re-innervating process (Figure 3)
1 Which of the following additional investigations may be helpful Choose ONE answer ONLY from the followingA Nerve conduction studiesB Creatine kinase assayC Muscle biopsyD SMN1 gene analysisE All of the above
2 What is the most likely cause of this childrsquos symptoms Choose ONE answer ONLY from the followingA Congenital myotonic dystrophyB Duchenne muscular dystrophyC PraderminusWilli syndromeD Spinal muscular atrophyE Mitochondrial myopathy
3 What is the mode of inheritance of this disease Choose ONE answer ONLY from the followingA X-linked recessiveB Autosomal recessiveC Autosomal dominantD MitochondrialE Sporadic
Case 5A 13-year-old girl presents with a 3-week history of fever up to 40degC night sweats and headache She has a reduced appetite with some weight loss She has no other specific symptoms She was on holiday in China 7 months ago On examination she looks well and has a temperature of 387degC There is no lymphadenopathy and no rashes Examination is entirely normal
Results of investigations are as follows
haemoglobin 126 gdl (120ndash160)
total white blood cell count 132 times 109litre (43ndash108)
neutrophil count 115 times 109litre (25ndash75)
Platelet count 244 times 109litre (150ndash400)
Blood film neutrophilia with left shift
erythrocyte sedimentation rate 63 mmh (1ndash20)
c-reactive protein 219 mglitre (0ndash5)
Blood culture Streptococcus intermedius
from anaerobic bottle only
csf culture negative
Magnetic resonance imaging (MRI) of the brain shows acute frontal sinusitis with a large intracranial frontal extra-dural empyema (Figure 4)
1 Which of the following would be appropriate management Choose ONE answer ONLY from the followingA A 12-week course of intravenous antibioticsB Drainage of the frontal sinus followed by 2 weeks of
intravenous antibioticsC Drainage of the empyema followed by 2 weeks of
intravenous antibioticsD Drainage of the empyema and the frontal sinus
followed by 2 weeks of oral antibiotics
1151
1152
1153
1154
1155
1156
1157
1158
1159
1200
50ms 1mV
Figure 3 electromyogram recording from the patient Figure 4 Parasagittal section from mri scan of patient
Paediatrics and child health 184 204 copy 2008 elsevier ltd all rights reserved
self-assessment
E Drainage of the empyema and the frontal sinus followed by 8 weeks of intravenous antibiotics
2 Streptococcus intermedius is a potential pathogen in which of the following infections Choose ONE answer ONLY from the followingA Liver abscessB Urinary tract infectionC MeningitisD Thoracic empyemaE Pneumonia
3 Which of the following statements regarding lsquopyrexia of unknown originrsquo in children is false Choose ONE answer ONLY from the followingA Malignancy is the underlying pathology in 5ndash15 of
casesB An aetiology will be found in over 90 of casesC The most common cause is infectionD A rheumatological cause is found in 10ndash20 of casesE Familial Mediterranean fever can occur in children of
non-Mediterranean ethnicity
Answers
Case 11 AThe anion gap is a useful tool to differentiate the causes of a metabolic acidosis It is calculated by the equation
Anion gap = [Na K ] [Cl HCO ]3+ + minus minus+ minus +
It represents the effect of unmeasured anions on the plasma pH and is normally 10ndash18 mmollitre
2 CMicrovillus inclusion disease is a severe autosomal recessive enteropathy that is typically apparent within hours or days after birth It is the second most common cause of protracted diarrhoea in the newborn after infectious causes It is characterized by severe yellow watery diarrhoea and malabsorption due to hypoplasia andor atrophy of the villi of the small intestine secondary to an inherited defect in the brush border membrane This results in severe dehydration malnutrition and metabolic acidosis due to bicarbonate loss from the gut
3 CDiagnosis of microvillus inclusion disease is made on small bowel biopsy Electron microscopy findings are of intracellular brush border inclusions and densely packed apical cytoplasmic vesicular bodies indicating microvillous atrophy There is no cure Treatment is supportive with total parenteral nutrition and consideration of small bowel transplantation
Further reAding
Goulet O ruemmele f causes and management of intestinal failure
in children Gastroenterology 2006 130(suppl 1) s16ndash28
rhoads Jm Vogler rc lacey sr et al microvillus inclusion disease
In vitro jejunal electrolyte transport Gastroenterology 1991
100 811ndash817
Case 21 CGianottindashCrosti syndrome is a distinct self-limiting rash commonly associated with viral infections in children between 2 and 6 years of age It presents as multiple pink to redminusbrown papules or papulovesicles which may be pruritic and can become confluent Gianotti and Crosti initially described the exanthema as associated with hepatitis B virus and they termed it papular acrodermatitis of childhood It can occur in several viral diseases eg hepatitis A B and C coxsackie viruses and cytomegalovirus
2 BHepatitis is a syndrome characterized by inflammation or injury of liver cells which may develop into cell necrosis and subsequently fibrosis andor cirrhosis Biochemically there are raised liver enzymes The degree of transaminase elevation does not correlate with the severity of the disease process Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of viral hepatitis
3 DHepatitis B infection is transmitted via blood sexually or vertically Infection may be acute or chronic Diagnostic markers are the presence of surface antigen (HBsAg) and HBV DNA The presence of e antigen (HBeAg) indicates high infectivity Infected newborns have a 95 risk of becoming carriers this risk decreases with infection acquired later in childhood Approximately 15ndash25 of HBV carriers will die from cirrhosis or hepatocellular carcinoma Extrahepatic findings are more common in older children and include membranous glomerulonephritis and GianottiminusCrosti syndrome Fulminant hepatic failure occurs in severe cases resulting in persistent jaundice encephalopathy and coagulopathy Management includes counselling family members monitoring for ongoing liver disease and consideration of antiviral therapy
Further reAding
Brandt O abeck d Gianotti r Burgdorf W Gianotti crosti
syndrome J Am Acad Dermatol 2006 54 136ndash145
slowik mK Jhaveri r hepatitis B and c viruses in infants and
young children Semin Pediatr Infect Dis 2005 16 296ndash305
Case 31 CHypercalcaemia is uncommon in infancy The most common symptoms in this age group are irritability vomiting and constipation It may be a manifestation of Williams syndrome vitamin D or calcium excess as well as disorders associated with reduced bone formation such as hypophosphatasia or increased bone resorption such as malignancy Occasionally
Paediatrics and child health 184 205 copy 2008 elsevier ltd all rights reserved
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-
SympoSium neonatology
this effect was maximal in the more immature brain Diazepam and clonazepam also resulted in a similar effect Midazolam and lidocaine were not tested in this study The combination of phenobarbitone or phenytoin with diazepam had a particularly profound effect on neurodegeneration
In summary recent data suggest that the commonly used AEDs for neonatal convulsions may in themselves cause neuro-degeneration due to apoptosis with lasting effects on develop-ment Many babies with neonatal convulsions are treated with at least two AEDs and this may produce more severe adverse effects than the seizures themselves
Practical management of neonatal seizures
Assimilation of these data and formulation of a rational policy is difficult when faced with a fitting neonate on an intensive care unit and pressure on the medical staff to lsquodo somethingrsquo but it is important to accept that sometimes doing nothing is preferable to using potentially dangerous drugs in a situation which does not warrant such intervention Many babies who have normal interseizure neurological clinical findings and whose seizures are relatively brief and infrequent probably do not need anticon-vulsant medication A normal or near-normal background EEG trace should reassure the clinician that anticonvulsants can be withheld
Some causes of neonatal convulsions are treatable such as meningitis hypoglycaemia hypocalcaemia and inborn errors of metabolism and each baby should be rapidly and carefully investigated for cause of the convulsions
In some babies clinical assessment of seizures is difficult ie when the baby is very sick small or paralyzed Sometimes it may be difficult to assess the significance of certain movement pat-terns Under these circumstances an EEG may prove to be very helpful In many units EEG is not available out of hours and a simple aEEG or CFM is strongly advised Modern instruments are very simple to apply and prolonged or frequent seizures should be identified with only moderate training The printout can be faxed to a more senior doctor if there is doubt as to what is shown on the trace
The balance of knowledge now is that frequent seizures cause additional damage to the developing brain and that treatment to abolish the seizures is warranted Unfortunately there is little evidence that the majority of seizures can be effectively termi-nated by current standard therapy Furthermore it appears that the more abnormal the background EEG the more difficult it is to control the seizures Nevertheless a written protocol for the management of neonatal convulsions is required on each unit Phenobarbitone and phenytoin remain the mainstay of treat-ment although their effectiveness is disappointing There is little to suggest that midazolam is more effective than lidocaine as third-line therapy but lidocaine is precluded if phenytoin has been previously used
In view of the anxiety as to the neurodegenerative effects on the immature brain of most anticonvulsants used in the neonatal period (particularly when multiple drugs are used) it is prefer-able to use only one drug to maximum dosage before introduc-ing a second In addition the duration of anticonvulsants should be minimized and the drugs stopped at the earliest opportu-nity It is my practice to stop anticonvulsants prior to discharge
paeDiatRiCS anD CHilD HealtH 184 18
from hospital if the baby is neurologically normal on clinical examination
REFEREnCES
1 Ronen gm penney S andrews W the epidemiology of clinical
neonatal seizures in newfoundland a population-based study
J Pediatr 1999 134 71ndash75
2 lanska mJ lanska DJ Baumann RJ et al a population-based study
of neonatal seizures in Fayette County Kentucky Neurology 1995
45 724ndash732
3 Rennie Jm Chorley g Boylan gB et al non-expert use of the
cerebral function monitor for neonatal seizure detection Arch Dis
Child Fetal Neonatal Ed 2004 89 F37ndashF40
4 tekgul H gauvreau K Soul J et al the current etoliologic profile
and neurodevelopmental outcome of seizures in term newborn
infants Pediatrics 2006 117 1270ndash1280
5 Surtees R Wolf n treatable neonatal epilepsy Arch Dis Child 2007
92 659ndash661
6 Ben-ari y Holmes gl effects of seizures on developmental
processes in the immature brain Lancet Neurol 2006 5 1055ndash
1063
7 Holmes gl gairsa Jl Chevassus-au-louis n et al Consequences of
neonatal seizures in the rat morphological and behavioral effects
Ann Neurol 1998 44 845ndash857
8 Stafstrom Ce Chronopoulos a thurber S et al age-dependent
cognitive and behavioural deficits following kainic-acid inducing
seizures Epilepsia 1993 34 420ndash432
9 Schmid R tandon p Stafstrom Ce et al effects of neonatal seizures
on subsequent seizure-induced brain injury Neurology 1999 53
1754ndash1761
10 Hoffmann aF Zhao Q Holmes gl Cognitive impairment following
status epilepticus and recurrent seizures during early development
support for the ldquotwo-hit hypothesisrdquo Epilepsy Behav 2004 5
873ndash877
11 Wirrell eC armstrong ea osman lD et al prolonged seizures
exacerbate perinatal hypoxic-ischemic brain damage Pediatr Res
2001 50 445ndash454
12 Carmo KB Barr p Drug treatment of neonatal seizures by
neonatologists and paediatric neurologists J Paediatr Child Health
2005 41 313ndash316
13 Hall Rt Hall FK Daily DK High-dose phenobarbital therapy in term
newborn infants with severe perinatal asphyxia a randomized
prospective study with three-year follow-up J Pediatr 1998 132
345ndash348
14 Boylan gB Rennie Jm pressler Rm et al phenobarbitone neonatal
seizures and video-eeg Arch Dis Child Fetal Neonatal Ed 2002 86
F165ndash170
15 painter mJ Scher mS Stein aD et al phenobarbital compared with
phenytoin for the treatment of neonatal seizures N Engl J Med
1999 341 485ndash489
16 Singh D Kumar p narang a a randomized controlled trial of
phenobarbital in neonates with hypoxic ischemic encephalopathy
J Matern Fetal Neonatal Med 2005 18 391ndash395
17 Castro Conde JR Borges H Domenech martinez e et al midazolam
in neonatal seizures with no response to phenobarbital Neurology
2005 64 876ndash879
1 copy 2008 elsevier ltd all rights reserved
SympoSium neonatology
18 malingre mm Van Rooij lgm Rademaker Cma et al Development
of an optimal lidocaine infusion strategy for neonatal seizures Eur
J Pediatr 2006 165 598ndash604
19 Sankar R painter mJ neonatal seizures after all these years we still
love what doesnrsquot work Neurology 2005 64 776ndash777
20 Diaz J Schain J Bailey Bg phenobarbital-induced brain growth
retardation in artificially reared rat pups Biol Neonate 1977 32 77ndash82
21 mattson RH phenobarbital toxicity in levy RH Dreifuss Fe
mattson RH et al eds antiepipeptic Drugs 3rd edn new york
Raven 1985 p 341ndash355
22 mikati ma Holmes gl Chronopoulos a et al phenobarbital
modifies seizure-related brain injury in the developing brain Ann
Neurol 1994 36 425ndash453
23 Bittigau p Sifringer m genz K et al antiepileptic drugs and
apoptotic neurodegeneration in the developing brain Proc Natl
Acad Sci U S A 2002 99 15089ndash15094
paeDiatRiCS anD CHilD HealtH 184 182
Practice points
bull the clinician needs to be aware that almost any repetitive
stereotype movement pattern can be a manifestation of
neonatal seizures
bull eeg is important in defining neonatal seizures
bull Frequent short-lived seizures have been shown to cause long-
term neurodevelopmental problems
bull Conventional anticonvulsant medication is ineffective in
abolishing neonatal seizures in greater than 50 of cases
bull there is evidence that exposure of the neonatal brain to
multiple anticonvulsants causes neuronal death
bull Future research is needed to evaluate more effective
anticonvulsants for treating this condition
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
Emotional support for families of sick neonatesMarina nicolaou
cristine Glazebrook
AbstractParents of sick neonates experience high levels of stress anxiety and
depression Most interventions with families of sick infants have focused
on fostering the motherndashinfant relationship through the provision of
information about infant developmental needs or through increased
motherndashinfant contact Many of these studies have reported improved
maternal well-being though there are some concerns about the scope
and practicality of large-scale interventions The few studies to have
prioritized emotional support for parents of sick neonates have pro-
duced encouraging results even interventions requiring relatively few re-
sources such as telephone support parent-to-parent support and group
support have been associated with reduced psychological morbidity for
parents The needs of parents can change throughout their infantrsquos hos-
pitalization and not all want or benefit from the provision of additional
support Thus neonatal intensive care units should aim to provide a
varied flexible and sustainable programme of support options Further
research should focus on the needs of fathers
Keywords mental health neonatal intensive care parents
The admission of an infant to neonatal care is acknowledged to be a source of considerable distress for families This review aims to explore evidence for the psychological impact on families of having an infant in neonatal intensive care and to identify evi-dence for the effectiveness of interventions to promote parental well-being It will conclude with recommendations for strategies to support parents of vulnerable infants and suggestions for fur-ther research
Psychological impact of neonatal care for parents
The majority of research examining the effect on parents of having a sick neonate has focused on families of premature or low birthweight infants Such research has found that parents with a sick neonate exhibit high levels of stress compared to normative samples and to parents of healthy full-term infants1 Singer et al2 examined the stress experienced by mothers of high-risk very low birthweight (VLBW) low-risk VLBW and term
Marina Nicolaou MPhil is a Teaching Assistant at the School of
Community Health Sciences University of Nottingham Nottingham UK
Cristine Glazebrook PhD is a Professor of Health Psychology at the School
of Community Health Sciences University of Nottingham Nottingham UK
PaeDiaTrics anD cHilD HealTH 184 196
infants Several self-report measures were used including the Brief Symptom Inventory the Parenting Stress Index (PSI) the Impact on Family Scale and the Family Inventory of Life Events and Changes (FILE) Mothers of VLBW infants had more psycho-logical distress at 1 month compared to mothers of term infants Mothers of high-risk VLBW infants also reported high psycho-logical distress at 2 years and high levels of parenting stress at 3 years Mothers have also been found to have higher stress levels compared to fathers Shaw et al3 examined the prevalence of acute stress disorder (ASD) in 40 parents whose infants were in the neonatal intensive care unit (NICU) Nearly half of the moth-ers (44) met the criteria for ASD although none of the fathers did Furthermore the severity of the symptoms (measured by the number of concurrent symptoms) was greater for the moth-ers than for the fathers3 The reasons behind this difference have been widely speculated with some believing that it is due to the mothersrsquo greater psychological involvement with the infant as evidenced by their general greater vulnerability to postpartum psychological disorder It could also reflect gender differences in coping style
Having an infant who requires intensive medical care repre-sents a significant emotional burden for families Not only is there extreme anxiety surrounding the infantrsquos health and distress for the childrsquos suffering there is also the unfamiliar and intimidating environment of the NICU to adjust to Hopper in her review of the literature identified sources of stress for parents of sick neo-nates as falling into three areas4 Situational factors included the severity of the infantrsquos illness and how parents adapted to the life crisis of having a sick infant Personal factors involved parental emotions about their roles and the instrumental and informa-tional support which were available to them The third area was classified as environmental sources of stress and included the environment of the NICU and the relationship between parents and members of staff This relationship has been examined by several studies in the nursing literature nurses are seen as ide-ally placed to provide the necessary support and information to parents with sick neonates However whilst some studies have shown that supportive and helpful hospital staff can have a posi-tive effect on parents other studies have highlighted the prob-lems and difficulties which can manifest It has been shown that parents and nurses often have very different ideas about issues eg the necessary skills and competencies needed in an NICU or the characteristics that make a lsquogood motherrsquo
Research has shown that there may be a relationship between high levels of parental stress and an increased likelihood of depression5 Postpartum depression is a psychiatric illness which appears in 10ndash15 of postpartum women Its reported preva-lence rates however have ranged from less than 10 up to 306 depending on the instruments used the population exam-ined and the timing of the research Several factors have been found to be associated with postpartum depression including poor social support and infant-related stressors6 Evidence indi-cates that postnatal depression may be underreported and this is of concern since the mental and psychological health of the mother can affect her relationship with her infant and thus the infantrsquos cognitive and emotional development5 Depressed moth-ers appear to look touch and talk to their infants less frequently and also appear to show fewer positive and more negative faces7 The vocalizations of mothers suffering with depression have also
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
been found to be less effective at promoting cognitive growth and learning in infants8
If researchers are interested in finding ways of providing sup-port for families of sick neonates then they must listen to what such families perceive their needs to be in order to avoid increas-ing anxiety and distress Furthermore the provision of appropri-ate support be it emotional informational or social will enhance parental coping abilities increase self-esteem and reduce anxiety It should be noted though that the research conducted around these issues has often taken lsquosupport needsrsquo as being synony-mous with lsquoinformation needsrsquo Such studies have examined the type the amount and quality of information that parents receive and perceive themselves as needing but have not explored in equal depth the perceived emotional support needs of families who have a sick infant In addition the needs of parents may change throughout their infantrsquos illness Ward examined the per-ceived needs of 52 parents of infants in an NICU9 Parents rated the needs of their hospitalized infant as most important along with the need to be reassured Interestingly they ranked their support needs as least important This research was conducted during the first week of the infantsrsquo hospitalization however which would explain the preoccupation of the parents with the infantrsquos health These results demonstrate that if researchers want to find ways of providing emotional support to parents of sick neonates they must be prepared not only to listen to parents but also to be flexible enough to satisfy the parentsrsquo changing needs and expectations
Interventions aimed at supporting parents
Most interventions that been evaluated in controlled studies have focused on supporting the motherndashinfant relationship and provid-ing information on infant development Many of these interven-tions have included the aim of improving the parental emotional state and thus psychological outcomes such as stress or anxi-ety have been assessed However few studies appear to include fathers This means that strategies implemented to provide emo-tional support to families of sick neonates are often derived from interventions tailored for mothers even though fathers may have different emotional needs
A wide range of interventions with mothers and infants has been evaluated in the NICU Increasing motherndashinfant contact through kangaroo care has been found to reduce maternal anxiety1011 and educational programmes delivered to fami-lies in the NICU have also been associated with reduced emo-tional difficulties in parents12ndash14 Kaaresen and colleagues implemented an intervention which consisted of eight sessions before discharge and four home visits all by trained nurses The sample included 71 premature infants in the intervention group 69 premature infants in the control group and 74 infants in the full-term control group The randomized controlled trial found that the intervention reduced parenting stress in both mothers and fathers of premature infants compared to controls to a level equivalent to parents in the term control group13 At 6 months corrected age mothers of preterm infants who had not received the intervention had total PSI scores which were 17 points higher than the mothers of infants born at term (an effect size of 057) A similar study evaluated the efficacy of an educationalndashbehavioural programmendashCreating Opportunities for
PaeDiaTrics anD cHilD HealTH 184 19
Parent Empowerment (COPE) ndash through a randomized controlled trial with 260 families of premature infants14 COPE was a four-phase educationalndashbehavioural programme which began as early as 2ndash4 d after mothers had given birth and continued until 1 week after discharge from the NICU The programme consisted of audiotaped and written infant behaviour information along with photographs which focused on common behaviours and characteristics of premature infants It also included various par-ent activities in the form of a four-phase workbook which aimed to assist mothers in the implementation of the experimental infor-mation COPE was found significantly to reduce maternal stress in the NICU as well as maternal anxiety and depressive symptoms after hospitalization In contrast a cluster randomized trial of a parenting intervention delivered to mothers of very premature infants from soon after birth showed no benefits for parenting stress1 The authors hypothesized that the intervention had not been of sufficient intensity particularly in the weeks surrounding discharge Neonatal care presents a significant barrier to parent-ing in the early weeks following a very preterm birth and so inter-ventions which focus on the developmental needs of infants and the parentndashchild relationship should particularly aim to support parents as they take on the parenting role There was also concern that the intervention had failed to reach those most at risk
Since large-scale projects can be costly to implement and may often fail to reach the families in most need it may be wiser to focus on intervention programmes which are more practical and easier to implement within a neonatal care setting Research has shown that even interventions which are based on one-off meet-ings with parents of sick neonates can be effective Jotzo and Poets examined the effect of an intervention programme aimed at reducing the severity of traumatic responses as a result of giv-ing birth prematurely15 Their programme consisted of a one-off intervention meeting along with additional psychological help throughout the hospitalization of the infant The meeting cov-ered a variety of issues including a reconstruction of the events shortly before and after the infantrsquos birth relaxation techniques discussion of coping strategies available resources and social support and support during emotional outbursts The measures used included the Impact of Event Scale (IES) and the Peritrau-matic Dissociative Experience Questionnaire At discharge the mothers who received the intervention were found to have a significantly lower traumatic impact as a result of premature birth Furthermore fewer mothers in the intervention group showed symptoms of clinically significant psychological trauma at discharge compared to mothers in the control group (36 vs 76)15 The lsquoParents Circle Programrsquo is another intervention with a similar structure16 This consisted of a 90 min session for parents with the aim of enhancing the developing relationship between parents and infants and to offer parents support A total of 104 parents (59 mothers and 45 fathers) and 44 members of hospital staff were asked to evaluate the programme and their results were analysed using content analysis Families reported gaining perspective on their situation feeling supported becom-ing aware of cues and optimizing interactions and becoming aware of available resources Parents and staff alike felt that participating in the intervention helped parents overcome the difficulties associated with the early time of their infantrsquos hos-pitalization Additional studies have also found positive results with fairly minimal interventions including discussion groups
7 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
in the NICU music during kangaroo care and pairing mothers of sick neonates with trained mothers who had been through similar experiences
Parent support programmes
Parent support programmes (PSPs) which are based in NICUs can provide parents with the opportunity to talk to parents who have been in similar situations and also to discuss their emo-tions with professionals who can help them cope with their situa-tion111718 The parent-to-parent support programme for mothers of preterm infants evaluated by Preyde and Ardal included edu-cational parental support group meetings and individual par-ent-to-parent support (primarily telephone support)19 Measures used included the Parental Stressor Scale NICU the State and the Trait Anxiety Inventories and the Beck Depression Inven-tory After 4 months of participation mothers in the intervention group reported lower levels of stress state anxiety and depres-sion compared to control group mothers The authors speculated however that the participants who were able to meet face to face with other parents were those who benefited the most Hurst conducted a comprehensive survey of an NICU-based PSP This PSP was provided in a variety of formats including a weekly parent support group hospital visitation and 24-h telephone sup-port20 Of the 477 participants 303 families used the PSP dur-ing a 2-year evaluation period with 78 using only one form of support and 18 using two forms Of a sub-sample of 48 parents asked to complete an evaluation of the PSP 92 stated that they would recommend such a programme to other parents Furthermore the majority of parents felt that it made them feel supported and helped them deal with their emotions20 This is an indication that such programmes can be very successful in sup-porting parents throughout their infantrsquos hospitalization It also shows that it can be beneficial to give parents several options and formats when it comes to such support services It is impor-tant to consider though that both the Hurst and the Preyde and Ardal studies found that some participants did not find the sup-port programmes helpful even reporting that they had caused them increased stress and anxiety Therefore it should not be assumed that support programmes will suit every individual and will provide the required support for all parents1920 NICUs need to be flexible enough to provide parents with a range of forms of support to choose from
The increased understanding of the strains that parents of sick neonates have to deal with has also led to efforts to improve customary practices in NICUs Family-centred care focuses on infants and their needs and attempts to redefine the relationship between parents and caregivers These practices strive to provide parents with support during their infantrsquos illness by focusing on freely sharing information and on the collaboration between parents and hospital staff Family-centred care has been found to be associated with several beneficial outcomes including improved parental satisfaction increased parental comfort staff satisfaction and decreased parental stress18 Research is already examining these practices and questioning how these can be improved further Such research reflects the increasing effort focused on lsquohumanizingrsquo the environment in NICUs in order to make parents feel more comfortable about spending time with their infants
PaeDiaTrics anD cHilD HealTH 184 19
Conclusion
Surprisingly few interventions have prioritized the provision of emotional support for parents of sick neonates or accounted for the changing needs and wishes of parents over the course of their infantrsquos care Large-scale supportive education-based inter-ventions have been shown to be effective in reducing parental distress However the feasibility and sustainability of such pro-grammes should also be considered Programmes which require significant additional resources can be expensive and there are also issues of training and quality control Interventions which require significant input from parents may also place additional burdens on families making them potentially less accessible to those most at risk Arguably the aim should be to explore ways of providing acceptable and effective informational support which could be complemented by emotional support from health professionals and from other parents in the unit Increasingly studies are exploring the use of computers and multimedia as an engaging flexible and cost-effective method of targeting indi-vidual needs and providing support and information Such com-puter-based and interactive multimedia interventions have been found to be successful with a range of patient groups and could therefore be examined as a complementary method of providing informational support to families with sick neonates
REfEREnCEs
1 Glazebrook c Marlow n israel c et al randomised trial of a
parenting intervention during neonatal intensive care Arch Dis Child
Fetal Neonatal Ed 2007 92 F438ndash443
2 singer lT salvator a Guo s collin M lilien l Baley J Maternal
psychological distress and parenting stress after the birth of a very
low-birth-weight infant JAMA 1999 281 799ndash805
3 shaw rJ Deblois T ikuta l Ginzburg K Fleisher B Koopman c
acute stress disorder among parents of infants in the neonatal
intensive care nursery Psychosomatics 2006 47 206ndash212
4 Hopper a sources of stress for parents of a sick neonate a
literature review Pediatr Nurs 2000 30 29ndash32
5 Davis l edwards H Mohay H wollin J The impact of very
premature birth on the psychological health of mothers Early Hum
Dev 2003 73 61ndash70
6 Bernazzani O saucier J-F David H Borgeat F Psychosocial
predictors of depressive symptomatology level in postpartum
women J Affect Disord 1997 46 39ndash49
7 Field T infants of depressed mothers Infant Behav Dev 1995 18
1ndash13
8 Kaplan Ps Bachorowski J-a Zarlengo-strouse P child-directed
speech produced by mothers with symptoms of depression fails
to promote associative learning in 4-month-old infants Child Dev
1999 70 560ndash570
9 ward K Perceived needs of parents of critically ill infants in
a neonatal intensive care unit (nicU) Pediatr Nurs 2001 27
281ndash286
10 lai Hl chen cJ Peng Tc et al randomized controlled trial of music
during kangaroo care on maternal state anxiety and preterm infantsrsquo
responses Int J Nurs Stud 2006 43 139ndash146
8 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
11 Tallandini Ma scalembra c Kangaroo mother care and mother-
premature infant dyadic interaction Infant Ment Health J 2006 27
251ndash275
12 Ohgi s Fukuda M akiyama T Gima H effect of an early intervention
programme on low birthweight infants with cerebral injuries
J Paediatr Child Health 2004 40 689ndash695
13 Kaaresen Pi ronning Ja Ulvund se Dahl lB a randomized
controlled trial of the effectiveness of an early-intervention program
in reducing parenting stress after preterm birth Pediatrics 2006
118 e9ndash19
14 Melnyk BM Feinstein nF alpert-Gillis l et al reducing premature
infantsrsquo length of stay and improving parentsrsquo mental health
outcomes with the creating opportunities for parent empowerment
(cOPe) neonatal intensive care unit program a randomized
controlled trial Pediatrics 2006 118 e1414ndash1427
15 Jotzo M Poets cF Helping parents cope with the trauma of
premature birth an evaluation of a trauma-preventive psychological
intervention Pediatrics 2005 115 915ndash919
16 Pearson J andersen K evaluation of a program to promote positive
parenting in the neonatal intensive care unit Neonatal Netw 2001
20 43ndash48
17 roman l lindsay J Boger r et al Parent-to-parent support
initiated in the neonatal intensive care unit Res Nurs Health 1995
18 385ndash394
18 Meyer ec coll cTG lester BM Boukydis cFZ McDonough sM Oh w
Family-based intervention improves maternal psychological well-
being and feeding interaction of preterm infants Pediatrics 1994
93 241ndash246
PaeDiaTrics anD cHilD HealTH 184 19
19 Preyde M ardal F effectiveness of a parent ldquobuddyrdquo program for
mothers of very preterm infants in a neonatal intensive care unit
CMAJ 2003 168 969ndash973
20 Hurst i One size does not fit all Parentsrsquo evaluations of a support
program in a newborn intensive care nursery J Perinat Neonatal
Nurs 2006 20 252ndash261
Practice points
bull Parents of sick neonates experience significant distress and
exhibit higher levels of stress anxiety and depression than
parents of healthy infants
bull educational support emotional support and increased
motherndashinfant contact have been shown to promote maternal
well-being
bull emotional support for fathers has been largely neglected in
the research literature
bull Parents benefit from a choice of supportive facilities which
could include face-to-face sessions with health professionals
telephone support hospital visitation parent-to-parent
support and unit-based group support meetings
bull Parentsrsquo support needs can change during their infantrsquos
hospitalization and not all parents want or benefit from the
provision of additional information and emotional support in
the neonatal unit
9 copy 2008 elsevier ltd all rights reserved
Personal Practice
When should enteral feeds be started in preterm infantsnicholas D embleton
AbstractPaediatricians are regularly faced with the question of when best to start
enteral feeds in preterm infants this is important as longer term out-
come may be compromised by sub-optimal nutrition in early life clinical
factors that may affect the decision to start and the risk and benefits
are discussed
Keywords breast milk feeding nutrition parenteral nutrition
Key points in the history
Alice is lsquonutritionally vulnerablersquo and whilst this may not be immediately apparent it will affect her long term outcome Her energy stores are extremely limited and consist primarily of pro-tein She has less than 5 fat and little energy associated with stored glycogen She is losing about 1 gkgd protein equivalent so she needs at least that and a minimum of 50ndash60 kcalkg of energy just to maintain the status quo let alone grow
Her weight is on the 25th centile Review of any antenatal his-tory may reveal whether fetal growth was normal Fetal growth retardation can occur with a weight greater than 10th centile The presence of antenatal absent or reversed end diastolic flow in the umbilical artery indicates poor gut blood flow This increases the risk of necrotizing enterocolitis (NEC) and might suggest a more cautious approach to starting feeds1
She has no important cardiovascular problems but if she were hypotensive gut blood flow may be low There is no umbilical
Nicholas D Embleton BSC (Hons) MBBS (Hons) MD FRCPCH is Consultant in
Neonatal Medicine at Newcastle Neonatal Service Royal Victoria
Infirmary Newcastle upon Tyne NE1 4LP UK
Should you start feeds at a day of age
alice was born following spontaneous labour at 30 weeksrsquo
gestation she weighed 1300 g and is now 18 h old she was
briefly ventilated and then extubated to continuous positive
airway pressure 12 h ago in 35 oxygen she has had caffeine
citrate but still has intermittent episodes of self-correcting
apnoea she was commenced on iv 10 dextrose but this was
replaced by a parenteral amino acid solution (referred to as
lsquotPnrsquo) along with intralipid at 0900 this morning serum glucose
is 11 mmoll and blood pressure is 42 systolic
PaeDiatrics anD cHilD HealtH 184 20
arterial catheter in situ but there is no good evidence that this should delay the decision to start feeds Her glucose is high but this is quite common in a baby like this Could this be a sign of sepsis Caffeine does not affect the incidence of NEC2 The great-est risk factor for NEC in this case is prematurity
What else might be found on examination
Up until 24 h ago she was swallowing large amounts of amniotic fluid What will have changed since then
General examination should confirm peripheral perfusion lsquogestaltrsquo view (does she look lsquowellrsquo) and cardiovascular status lsquoBowel soundsrsquo are not usually helpful
The most important variable likely to affect gut perfusion is the arterial duct Precordial lsquoheaversquo and a loud murmur are sug-gestive but it is possible to have a significant ductal shunt in a baby with a normal examination Cardiac ultrasound will con-firm this diagnosis It might be better to treat a large shunt first with indometacin and to delay starting feeds for a further 24 h
It is not possible to assess gut perfusion clinically but normal perfusion elsewhere (adequate urine output usually indicates adequate renal perfusion) would be reassuring Most preterm babies have a few abdominal lsquoloopsrsquo visible but a distended abdomen with many palpable loops suggests ileus This might be secondary to sepsis or poor gut blood flow Preterm babies do not pass much meconium in the first 24ndash48 h
Balance of risks between starting and withholding feeds
Alice requires 35ndash4 gkgd of protein and 120 kcalkgd to grow3 This will initially be provided parenterally Delaying feeds increases the risk of gut villous atrophy and prolongs the need for lsquototal parenteral nutrition (TPN)rsquo TPN requires intravenous access and so increases the risk of sepsis and when prolonged use is required combined with the lack of enteral feeding may result in hepatic impairment
Delaying feeds may allow a gut that has been chronically under-perfused to re-establish more normal perfusion although normal gut endocrine function digestive enzyme upregulation and motility require a source of intraluminal nutrients1 A recent study suggested benefit from delaying the introduction of feeds4 but methodologi-cal problems exist5 Although a Cochrane meta-analysis suggested no benefit only two studies were included6 A large UK-based trial is examining the effect of early or late feeding in preterm infants who were born growth retarded following identification of antena-tal absent or reversed end diastolic flow in the umbilical artery7
When starting feeds what volume should be used
There are no good data to guide this decision We start with 24 mlkg (1 mlkgh) and then increase by this amount each day Most babies achieve full enteral feeds (ge150 mlkgd) by a week of age Feeding guidelines improve the outcome8 Measure-ment or assessment of gastric aspirates is not consistently useful in predicting subsequent feeding intolerance or development of NEC Aspirate volumes equivalent to or sometimes greater than the amount given in the preceding 1ndash2 h are usually normal Most aspirates have a greenish colour Thick bloody or intensely bile-stained aspirates require detailed assessment
0 copy 2008 elsevier ltd all rights reserved
Personal Practice
What else affects decisions and outcome
Feeding success is affected by sepsis and NEC Scrupulous atten-tion should be paid to hand washing and intravenous access and blood sampling should be minimized There is no good evidence to support the routine use of pro-kinetic agents or H2 blockers
The most important clinical intervention affecting the occur-rence of NEC is the use of breast milk9 All efforts should be directed at persuading parents of the benefits and supporting the process Some clinicians delay starting feeds for a further 24 h whilst expressed breast milk becomes available Donor breast milk might be equally efficacious10
RefeRenceS
1 Dorling J Kempley s leaf a Feeding growth restricted preterm
infants with abnormal antenatal Doppler results Arch Dis Child Fetal
Neonatal Ed 2005 90 F359ndash363
2 schmidt B roberts rs Davis P et al caffeine therapy for apnea of
prematurity N Engl J Med 2006 354 2112ndash2121
PaeDiatrics anD cHilD HealtH 184 20
3 embleton nD Pang n cooke rJ Postnatal malnutrition and growth
retardation an inevitable consequence of current recommendations
in preterm infants Pediatrics 2001 107 270ndash273
4 Berseth cl Bisquera Ja Paje VU Prolonging small feeding volumes
early in life decreases the incidence of necrotizing enterocolitis in
very low birth weight infants Pediatrics 2003 111 529ndash534
5 Menon G Boyle eM embleton nD et al introduction of enteral
feeds in preterm infants Pediatrics 2004 114 327ndash328
6 Kennedy Ka tyson Je chamnanvanikij s early versus delayed
initiation of progressive enteral feedings for parenterally fed low
birth weight or preterm infants Cochrane Database Syst Rev 2000
cD001970
7 wwwnpeuoxacukadept
8 Patole sK de Klerk n impact of standardised feeding regimens on
incidence of neonatal necrotising enterocolitis a systematic review
and meta-analysis of observational studies Arch Dis Child Fetal
Neonatal Ed 2005 90 F147ndash151
9 lucas a cole tJ Breast milk and neonatal necrotising enterocolitis
Lancet 1990 336 1519ndash1523
10 Boyd ca Quigley Ma Brocklehurst P Donor breast milk versus
infant formula for preterm infants systematic review and meta-
analysis Arch Dis Child Fetal Neonatal Ed 2007 92 F169ndash175
1 copy 2008 elsevier ltd all rights reserved
self-assessment
Case 1A term male infant born to consanguineous parents is assessed at 24 h of age due to poor feeding profuse yellow watery diar-rhoea and irritability He weighed 32 kg at birth and delivery was uneventful There was no polyhydramnios He has been breastfed since birth On examination he is pale with a non-tender but distended abdomen and reduced bowel sounds His weight is 275 kg and he looks dehydrated Examination is otherwise normal
Initial investigations (normal values in parentheses) showed
sodium 149 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 65 mmollitre (25ndash75)
creatinine 147 μmollitre (40ndash110)
chloride 119 mmollitre (95ndash105)
haemoglobin 172 gdl (140ndash200)
White blood cell count 80 times 109litre (100ndash260)
Platelet count 302 times 109litre (150ndash400)
arterial blood gas
ph 720 (730ndash745)
PcO2 23 kPa (46ndash60)
Bicarbonate 68 mmollitre (220ndash260)
Base excess minus186 mmollitre (minus20 to +20)
lactate 59 mmollitre (06ndash24)
An abdominal X-ray shows distended bowel loops with no intramural thickening or pneumoperitoneum (Figure 1)
He was given nil by mouth and received intravenous fluids and antibiotics His dehydration improved but the metabolic acidosis and diarrhoea persisted despite receiving no enteral feeds and the commencement of total parenteral nutrition Blood and stool cultures were negative
1 Which of the following best describes these results Choose ONE answer ONLY from the followingA Hypernatraemia hyperchloraemic metabolic acidosis
with increased anion gapB Hypernatraemia hyperchloraemic metabolic acidosis
with normal anion gap
Manish Sadarangani BM BCh MA MRCPCH is Clinical Research Fellow
at the Department of Paediatrics University of Oxford Centre for
Clinical Vaccinology and Tropical Medicine Churchill Hospital
Oxford OX3 7LJ UK
Shabna Rajapaksa MB BChir MA MRCPCH is Specialist Registrar in
Paediatrics at the Paediatric Intensive Care Unit John Radcliffe
Hospital Oxford OX3 9DU UK
Nicholas Mann MD FRCP FRCPCH DCH is Consultant Paediatrician at the
Department of Paediatrics Royal Berkshire Hospital Reading RG1
5AN UK
self-assessment
C Hypernatraemic dehydration and compensated metabolic acidosis
D Acute renal failureE Renal tubular acidosis
2 What is the likely diagnosis Choose ONE answer ONLY from the followingA Hirschsprung disease ndash long segmentB Cystic fibrosis with meconium ileusC Microvillus inclusion diseaseD Cowrsquos milk protein intoleranceE Lactose intolerance
3 What is the investigation of choice Choose ONE answer ONLY from the followingA Rectal biopsy with staining for acetylcholine receptorsB Immunoreactive trypsinC Gastrointestinal endoscopy and biopsyD Stool microscopy and cultureE Stool reducing substances
Case 2A 4-year-old boy presents with a 3 d history of jaundice and a florid rash He has had orange urine and there is no change in his stool colour His family originate from Kosovo and have lived in the UK for the last 8 years He has never left the UK There is no history of blood transfusion or sex-ual abuse The grandmother was recently diagnosed with hepatitis B
On examination he is well apyrexial and mildly jaundiced with cervical and axillary lymphadenopathy He has an exten-sive papular rash over the face extremities and trunk (Figure 2) There is 3 cm hepatomegaly with no splenomegaly or ascites Examination is otherwise normal
Figure 1 abdominal X-ray of baby
Paediatrics and child health 184 202 copy 2008 elsevier ltd all rights reserved
self-assessment
Initial investigations are as follows
haemoglobin 110 gdl (113ndash135)
White blood cell count 108 times 109litre (50ndash150)
Platelet count 278 times 109litre (150ndash400)
inr 10 (08ndash12)
aPt ratio 10 (08ndash13)
sodium 140 mmollitre (135ndash145)
Potassium 42 mmollitre (35ndash50)
Urea 56 mmollitre (25ndash75)
creatinine 65 μmollitre (45ndash120)
total bilirubin 66 μmollitre (0ndash15)
conjugated bilirubin 23 μmollitre (0ndash10)
alanine aminotransferase (alt) 2033 iUlitre (0ndash35)
alkaline phosphatase 987 iUlitre (71ndash234)
Gamma-glutamyl transferase (GGt) 870 iUlitre (0ndash51)
1 What is the name of this rash Choose ONE answer ONLY from the followingA Erythema multiformeB Erythema migransC GianottiminusCrosti syndromeD EczemaE Dermatitis herpetiformis
2 What is the most likely diagnosis Choose ONE Answer ONLY from the followingA Autoimmune hepatitisB Hepatitis BC Hepatitis DD Wilson diseaseE Alpha-1 antitrypsin deficiency
3 What is the best means of management Choose ONE answer ONLY from the followingA Isolation until the jaundice disappearsB ImmunosuppressionC Copper chelating agents and genetic counsellingD Patient and family education with consideration of
antiviral agentsE Liver transplantation
Case 3A 10-month-old boy presents with 3 weeks of vomiting and constipation ndash he is passing hard stools every 2ndash3 days He has fallen from the 9th to below the 04th centile in the last 6 weeks He passed meconium within the first 24 h of life On examina-tion he looks pale and there are some dysmorphic features ndash a short nose long philtrum and wide mouth He has normal heart sounds with a grade 3 ejection systolic murmur loudest at the upper right sternal edge Examination is otherwise normal
Initial investigations are as follows
haemoglobin 91 gdl (113ndash141)
total white blood cell count 124 times 109litre (60ndash170)
Platelet count 407 times 109litre (150ndash400)
sodium 144 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 78 mmollitre (25ndash75)
creatinine 78 μmollitre (45ndash120)
albumin 52 glitre (35ndash50)
corrected calcium 384 mmollitre (238ndash263)
Phosphate 167 mmollitre (099ndash157)
1 What is the most likely diagnosis Choose ONE answer ONLY from the followingA HyperparathyroidismB Acute leukaemiaC Williams syndromeD Hypervitaminosis DE Familial hypocalciuric hypercalcaemia
2 Which investigation would be most useful in establishing the diagnosis Choose ONE answer ONLY from the followingA Intact parathyroid hormone assayB Blood filmC Fluorescent in-situ hybridization for 7q1123 deletionD 25-hydroxyvitamin D assayE Urine calciumcreatinine ratio
3 Which of the following treatments would not be suitable for this patient Choose ONE answer ONLY from the followingA Low calcium dietB Normal saline infusionC FurosemideD CorticosteroidsE Bisphosphonates
Case 4A 10-week-old girl presents with a 2-day history of poor feed-ing Her mother has been concerned about weakness since birth She only has a flicker of movement in the arms none in the legs and has a weak cry She has been passing urine and opening her bowels normally She was born at full term by normal delivery and did not require any resuscitation at birth Normal fetal movements were felt antenatally and there was no polyhydramnios She is the first child of non- consanguineous parents and there is no significant family his-tory On examination she is alert and fixing and following appropriately She has a weak cry and a weak suck There is reduced central and peripheral tone with marked head lag
Figure 2 rash found on examination
Paediatrics and child health 184 203 copy 2008 elsevier ltd all rights reserved
self-assessment
Muscle power is grade 3 out of 5 in the arms and legs There is no muscle or tongue fasciculation and she has absent reflexes throughout The remainder of the examination is normal
Electromyogram shows irregular polyphasic motor unit potentials with marked instability consistent with a dener-vating and re-innervating process (Figure 3)
1 Which of the following additional investigations may be helpful Choose ONE answer ONLY from the followingA Nerve conduction studiesB Creatine kinase assayC Muscle biopsyD SMN1 gene analysisE All of the above
2 What is the most likely cause of this childrsquos symptoms Choose ONE answer ONLY from the followingA Congenital myotonic dystrophyB Duchenne muscular dystrophyC PraderminusWilli syndromeD Spinal muscular atrophyE Mitochondrial myopathy
3 What is the mode of inheritance of this disease Choose ONE answer ONLY from the followingA X-linked recessiveB Autosomal recessiveC Autosomal dominantD MitochondrialE Sporadic
Case 5A 13-year-old girl presents with a 3-week history of fever up to 40degC night sweats and headache She has a reduced appetite with some weight loss She has no other specific symptoms She was on holiday in China 7 months ago On examination she looks well and has a temperature of 387degC There is no lymphadenopathy and no rashes Examination is entirely normal
Results of investigations are as follows
haemoglobin 126 gdl (120ndash160)
total white blood cell count 132 times 109litre (43ndash108)
neutrophil count 115 times 109litre (25ndash75)
Platelet count 244 times 109litre (150ndash400)
Blood film neutrophilia with left shift
erythrocyte sedimentation rate 63 mmh (1ndash20)
c-reactive protein 219 mglitre (0ndash5)
Blood culture Streptococcus intermedius
from anaerobic bottle only
csf culture negative
Magnetic resonance imaging (MRI) of the brain shows acute frontal sinusitis with a large intracranial frontal extra-dural empyema (Figure 4)
1 Which of the following would be appropriate management Choose ONE answer ONLY from the followingA A 12-week course of intravenous antibioticsB Drainage of the frontal sinus followed by 2 weeks of
intravenous antibioticsC Drainage of the empyema followed by 2 weeks of
intravenous antibioticsD Drainage of the empyema and the frontal sinus
followed by 2 weeks of oral antibiotics
1151
1152
1153
1154
1155
1156
1157
1158
1159
1200
50ms 1mV
Figure 3 electromyogram recording from the patient Figure 4 Parasagittal section from mri scan of patient
Paediatrics and child health 184 204 copy 2008 elsevier ltd all rights reserved
self-assessment
E Drainage of the empyema and the frontal sinus followed by 8 weeks of intravenous antibiotics
2 Streptococcus intermedius is a potential pathogen in which of the following infections Choose ONE answer ONLY from the followingA Liver abscessB Urinary tract infectionC MeningitisD Thoracic empyemaE Pneumonia
3 Which of the following statements regarding lsquopyrexia of unknown originrsquo in children is false Choose ONE answer ONLY from the followingA Malignancy is the underlying pathology in 5ndash15 of
casesB An aetiology will be found in over 90 of casesC The most common cause is infectionD A rheumatological cause is found in 10ndash20 of casesE Familial Mediterranean fever can occur in children of
non-Mediterranean ethnicity
Answers
Case 11 AThe anion gap is a useful tool to differentiate the causes of a metabolic acidosis It is calculated by the equation
Anion gap = [Na K ] [Cl HCO ]3+ + minus minus+ minus +
It represents the effect of unmeasured anions on the plasma pH and is normally 10ndash18 mmollitre
2 CMicrovillus inclusion disease is a severe autosomal recessive enteropathy that is typically apparent within hours or days after birth It is the second most common cause of protracted diarrhoea in the newborn after infectious causes It is characterized by severe yellow watery diarrhoea and malabsorption due to hypoplasia andor atrophy of the villi of the small intestine secondary to an inherited defect in the brush border membrane This results in severe dehydration malnutrition and metabolic acidosis due to bicarbonate loss from the gut
3 CDiagnosis of microvillus inclusion disease is made on small bowel biopsy Electron microscopy findings are of intracellular brush border inclusions and densely packed apical cytoplasmic vesicular bodies indicating microvillous atrophy There is no cure Treatment is supportive with total parenteral nutrition and consideration of small bowel transplantation
Further reAding
Goulet O ruemmele f causes and management of intestinal failure
in children Gastroenterology 2006 130(suppl 1) s16ndash28
rhoads Jm Vogler rc lacey sr et al microvillus inclusion disease
In vitro jejunal electrolyte transport Gastroenterology 1991
100 811ndash817
Case 21 CGianottindashCrosti syndrome is a distinct self-limiting rash commonly associated with viral infections in children between 2 and 6 years of age It presents as multiple pink to redminusbrown papules or papulovesicles which may be pruritic and can become confluent Gianotti and Crosti initially described the exanthema as associated with hepatitis B virus and they termed it papular acrodermatitis of childhood It can occur in several viral diseases eg hepatitis A B and C coxsackie viruses and cytomegalovirus
2 BHepatitis is a syndrome characterized by inflammation or injury of liver cells which may develop into cell necrosis and subsequently fibrosis andor cirrhosis Biochemically there are raised liver enzymes The degree of transaminase elevation does not correlate with the severity of the disease process Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of viral hepatitis
3 DHepatitis B infection is transmitted via blood sexually or vertically Infection may be acute or chronic Diagnostic markers are the presence of surface antigen (HBsAg) and HBV DNA The presence of e antigen (HBeAg) indicates high infectivity Infected newborns have a 95 risk of becoming carriers this risk decreases with infection acquired later in childhood Approximately 15ndash25 of HBV carriers will die from cirrhosis or hepatocellular carcinoma Extrahepatic findings are more common in older children and include membranous glomerulonephritis and GianottiminusCrosti syndrome Fulminant hepatic failure occurs in severe cases resulting in persistent jaundice encephalopathy and coagulopathy Management includes counselling family members monitoring for ongoing liver disease and consideration of antiviral therapy
Further reAding
Brandt O abeck d Gianotti r Burgdorf W Gianotti crosti
syndrome J Am Acad Dermatol 2006 54 136ndash145
slowik mK Jhaveri r hepatitis B and c viruses in infants and
young children Semin Pediatr Infect Dis 2005 16 296ndash305
Case 31 CHypercalcaemia is uncommon in infancy The most common symptoms in this age group are irritability vomiting and constipation It may be a manifestation of Williams syndrome vitamin D or calcium excess as well as disorders associated with reduced bone formation such as hypophosphatasia or increased bone resorption such as malignancy Occasionally
Paediatrics and child health 184 205 copy 2008 elsevier ltd all rights reserved
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-
SympoSium neonatology
18 malingre mm Van Rooij lgm Rademaker Cma et al Development
of an optimal lidocaine infusion strategy for neonatal seizures Eur
J Pediatr 2006 165 598ndash604
19 Sankar R painter mJ neonatal seizures after all these years we still
love what doesnrsquot work Neurology 2005 64 776ndash777
20 Diaz J Schain J Bailey Bg phenobarbital-induced brain growth
retardation in artificially reared rat pups Biol Neonate 1977 32 77ndash82
21 mattson RH phenobarbital toxicity in levy RH Dreifuss Fe
mattson RH et al eds antiepipeptic Drugs 3rd edn new york
Raven 1985 p 341ndash355
22 mikati ma Holmes gl Chronopoulos a et al phenobarbital
modifies seizure-related brain injury in the developing brain Ann
Neurol 1994 36 425ndash453
23 Bittigau p Sifringer m genz K et al antiepileptic drugs and
apoptotic neurodegeneration in the developing brain Proc Natl
Acad Sci U S A 2002 99 15089ndash15094
paeDiatRiCS anD CHilD HealtH 184 182
Practice points
bull the clinician needs to be aware that almost any repetitive
stereotype movement pattern can be a manifestation of
neonatal seizures
bull eeg is important in defining neonatal seizures
bull Frequent short-lived seizures have been shown to cause long-
term neurodevelopmental problems
bull Conventional anticonvulsant medication is ineffective in
abolishing neonatal seizures in greater than 50 of cases
bull there is evidence that exposure of the neonatal brain to
multiple anticonvulsants causes neuronal death
bull Future research is needed to evaluate more effective
anticonvulsants for treating this condition
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
Emotional support for families of sick neonatesMarina nicolaou
cristine Glazebrook
AbstractParents of sick neonates experience high levels of stress anxiety and
depression Most interventions with families of sick infants have focused
on fostering the motherndashinfant relationship through the provision of
information about infant developmental needs or through increased
motherndashinfant contact Many of these studies have reported improved
maternal well-being though there are some concerns about the scope
and practicality of large-scale interventions The few studies to have
prioritized emotional support for parents of sick neonates have pro-
duced encouraging results even interventions requiring relatively few re-
sources such as telephone support parent-to-parent support and group
support have been associated with reduced psychological morbidity for
parents The needs of parents can change throughout their infantrsquos hos-
pitalization and not all want or benefit from the provision of additional
support Thus neonatal intensive care units should aim to provide a
varied flexible and sustainable programme of support options Further
research should focus on the needs of fathers
Keywords mental health neonatal intensive care parents
The admission of an infant to neonatal care is acknowledged to be a source of considerable distress for families This review aims to explore evidence for the psychological impact on families of having an infant in neonatal intensive care and to identify evi-dence for the effectiveness of interventions to promote parental well-being It will conclude with recommendations for strategies to support parents of vulnerable infants and suggestions for fur-ther research
Psychological impact of neonatal care for parents
The majority of research examining the effect on parents of having a sick neonate has focused on families of premature or low birthweight infants Such research has found that parents with a sick neonate exhibit high levels of stress compared to normative samples and to parents of healthy full-term infants1 Singer et al2 examined the stress experienced by mothers of high-risk very low birthweight (VLBW) low-risk VLBW and term
Marina Nicolaou MPhil is a Teaching Assistant at the School of
Community Health Sciences University of Nottingham Nottingham UK
Cristine Glazebrook PhD is a Professor of Health Psychology at the School
of Community Health Sciences University of Nottingham Nottingham UK
PaeDiaTrics anD cHilD HealTH 184 196
infants Several self-report measures were used including the Brief Symptom Inventory the Parenting Stress Index (PSI) the Impact on Family Scale and the Family Inventory of Life Events and Changes (FILE) Mothers of VLBW infants had more psycho-logical distress at 1 month compared to mothers of term infants Mothers of high-risk VLBW infants also reported high psycho-logical distress at 2 years and high levels of parenting stress at 3 years Mothers have also been found to have higher stress levels compared to fathers Shaw et al3 examined the prevalence of acute stress disorder (ASD) in 40 parents whose infants were in the neonatal intensive care unit (NICU) Nearly half of the moth-ers (44) met the criteria for ASD although none of the fathers did Furthermore the severity of the symptoms (measured by the number of concurrent symptoms) was greater for the moth-ers than for the fathers3 The reasons behind this difference have been widely speculated with some believing that it is due to the mothersrsquo greater psychological involvement with the infant as evidenced by their general greater vulnerability to postpartum psychological disorder It could also reflect gender differences in coping style
Having an infant who requires intensive medical care repre-sents a significant emotional burden for families Not only is there extreme anxiety surrounding the infantrsquos health and distress for the childrsquos suffering there is also the unfamiliar and intimidating environment of the NICU to adjust to Hopper in her review of the literature identified sources of stress for parents of sick neo-nates as falling into three areas4 Situational factors included the severity of the infantrsquos illness and how parents adapted to the life crisis of having a sick infant Personal factors involved parental emotions about their roles and the instrumental and informa-tional support which were available to them The third area was classified as environmental sources of stress and included the environment of the NICU and the relationship between parents and members of staff This relationship has been examined by several studies in the nursing literature nurses are seen as ide-ally placed to provide the necessary support and information to parents with sick neonates However whilst some studies have shown that supportive and helpful hospital staff can have a posi-tive effect on parents other studies have highlighted the prob-lems and difficulties which can manifest It has been shown that parents and nurses often have very different ideas about issues eg the necessary skills and competencies needed in an NICU or the characteristics that make a lsquogood motherrsquo
Research has shown that there may be a relationship between high levels of parental stress and an increased likelihood of depression5 Postpartum depression is a psychiatric illness which appears in 10ndash15 of postpartum women Its reported preva-lence rates however have ranged from less than 10 up to 306 depending on the instruments used the population exam-ined and the timing of the research Several factors have been found to be associated with postpartum depression including poor social support and infant-related stressors6 Evidence indi-cates that postnatal depression may be underreported and this is of concern since the mental and psychological health of the mother can affect her relationship with her infant and thus the infantrsquos cognitive and emotional development5 Depressed moth-ers appear to look touch and talk to their infants less frequently and also appear to show fewer positive and more negative faces7 The vocalizations of mothers suffering with depression have also
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
been found to be less effective at promoting cognitive growth and learning in infants8
If researchers are interested in finding ways of providing sup-port for families of sick neonates then they must listen to what such families perceive their needs to be in order to avoid increas-ing anxiety and distress Furthermore the provision of appropri-ate support be it emotional informational or social will enhance parental coping abilities increase self-esteem and reduce anxiety It should be noted though that the research conducted around these issues has often taken lsquosupport needsrsquo as being synony-mous with lsquoinformation needsrsquo Such studies have examined the type the amount and quality of information that parents receive and perceive themselves as needing but have not explored in equal depth the perceived emotional support needs of families who have a sick infant In addition the needs of parents may change throughout their infantrsquos illness Ward examined the per-ceived needs of 52 parents of infants in an NICU9 Parents rated the needs of their hospitalized infant as most important along with the need to be reassured Interestingly they ranked their support needs as least important This research was conducted during the first week of the infantsrsquo hospitalization however which would explain the preoccupation of the parents with the infantrsquos health These results demonstrate that if researchers want to find ways of providing emotional support to parents of sick neonates they must be prepared not only to listen to parents but also to be flexible enough to satisfy the parentsrsquo changing needs and expectations
Interventions aimed at supporting parents
Most interventions that been evaluated in controlled studies have focused on supporting the motherndashinfant relationship and provid-ing information on infant development Many of these interven-tions have included the aim of improving the parental emotional state and thus psychological outcomes such as stress or anxi-ety have been assessed However few studies appear to include fathers This means that strategies implemented to provide emo-tional support to families of sick neonates are often derived from interventions tailored for mothers even though fathers may have different emotional needs
A wide range of interventions with mothers and infants has been evaluated in the NICU Increasing motherndashinfant contact through kangaroo care has been found to reduce maternal anxiety1011 and educational programmes delivered to fami-lies in the NICU have also been associated with reduced emo-tional difficulties in parents12ndash14 Kaaresen and colleagues implemented an intervention which consisted of eight sessions before discharge and four home visits all by trained nurses The sample included 71 premature infants in the intervention group 69 premature infants in the control group and 74 infants in the full-term control group The randomized controlled trial found that the intervention reduced parenting stress in both mothers and fathers of premature infants compared to controls to a level equivalent to parents in the term control group13 At 6 months corrected age mothers of preterm infants who had not received the intervention had total PSI scores which were 17 points higher than the mothers of infants born at term (an effect size of 057) A similar study evaluated the efficacy of an educationalndashbehavioural programmendashCreating Opportunities for
PaeDiaTrics anD cHilD HealTH 184 19
Parent Empowerment (COPE) ndash through a randomized controlled trial with 260 families of premature infants14 COPE was a four-phase educationalndashbehavioural programme which began as early as 2ndash4 d after mothers had given birth and continued until 1 week after discharge from the NICU The programme consisted of audiotaped and written infant behaviour information along with photographs which focused on common behaviours and characteristics of premature infants It also included various par-ent activities in the form of a four-phase workbook which aimed to assist mothers in the implementation of the experimental infor-mation COPE was found significantly to reduce maternal stress in the NICU as well as maternal anxiety and depressive symptoms after hospitalization In contrast a cluster randomized trial of a parenting intervention delivered to mothers of very premature infants from soon after birth showed no benefits for parenting stress1 The authors hypothesized that the intervention had not been of sufficient intensity particularly in the weeks surrounding discharge Neonatal care presents a significant barrier to parent-ing in the early weeks following a very preterm birth and so inter-ventions which focus on the developmental needs of infants and the parentndashchild relationship should particularly aim to support parents as they take on the parenting role There was also concern that the intervention had failed to reach those most at risk
Since large-scale projects can be costly to implement and may often fail to reach the families in most need it may be wiser to focus on intervention programmes which are more practical and easier to implement within a neonatal care setting Research has shown that even interventions which are based on one-off meet-ings with parents of sick neonates can be effective Jotzo and Poets examined the effect of an intervention programme aimed at reducing the severity of traumatic responses as a result of giv-ing birth prematurely15 Their programme consisted of a one-off intervention meeting along with additional psychological help throughout the hospitalization of the infant The meeting cov-ered a variety of issues including a reconstruction of the events shortly before and after the infantrsquos birth relaxation techniques discussion of coping strategies available resources and social support and support during emotional outbursts The measures used included the Impact of Event Scale (IES) and the Peritrau-matic Dissociative Experience Questionnaire At discharge the mothers who received the intervention were found to have a significantly lower traumatic impact as a result of premature birth Furthermore fewer mothers in the intervention group showed symptoms of clinically significant psychological trauma at discharge compared to mothers in the control group (36 vs 76)15 The lsquoParents Circle Programrsquo is another intervention with a similar structure16 This consisted of a 90 min session for parents with the aim of enhancing the developing relationship between parents and infants and to offer parents support A total of 104 parents (59 mothers and 45 fathers) and 44 members of hospital staff were asked to evaluate the programme and their results were analysed using content analysis Families reported gaining perspective on their situation feeling supported becom-ing aware of cues and optimizing interactions and becoming aware of available resources Parents and staff alike felt that participating in the intervention helped parents overcome the difficulties associated with the early time of their infantrsquos hos-pitalization Additional studies have also found positive results with fairly minimal interventions including discussion groups
7 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
in the NICU music during kangaroo care and pairing mothers of sick neonates with trained mothers who had been through similar experiences
Parent support programmes
Parent support programmes (PSPs) which are based in NICUs can provide parents with the opportunity to talk to parents who have been in similar situations and also to discuss their emo-tions with professionals who can help them cope with their situa-tion111718 The parent-to-parent support programme for mothers of preterm infants evaluated by Preyde and Ardal included edu-cational parental support group meetings and individual par-ent-to-parent support (primarily telephone support)19 Measures used included the Parental Stressor Scale NICU the State and the Trait Anxiety Inventories and the Beck Depression Inven-tory After 4 months of participation mothers in the intervention group reported lower levels of stress state anxiety and depres-sion compared to control group mothers The authors speculated however that the participants who were able to meet face to face with other parents were those who benefited the most Hurst conducted a comprehensive survey of an NICU-based PSP This PSP was provided in a variety of formats including a weekly parent support group hospital visitation and 24-h telephone sup-port20 Of the 477 participants 303 families used the PSP dur-ing a 2-year evaluation period with 78 using only one form of support and 18 using two forms Of a sub-sample of 48 parents asked to complete an evaluation of the PSP 92 stated that they would recommend such a programme to other parents Furthermore the majority of parents felt that it made them feel supported and helped them deal with their emotions20 This is an indication that such programmes can be very successful in sup-porting parents throughout their infantrsquos hospitalization It also shows that it can be beneficial to give parents several options and formats when it comes to such support services It is impor-tant to consider though that both the Hurst and the Preyde and Ardal studies found that some participants did not find the sup-port programmes helpful even reporting that they had caused them increased stress and anxiety Therefore it should not be assumed that support programmes will suit every individual and will provide the required support for all parents1920 NICUs need to be flexible enough to provide parents with a range of forms of support to choose from
The increased understanding of the strains that parents of sick neonates have to deal with has also led to efforts to improve customary practices in NICUs Family-centred care focuses on infants and their needs and attempts to redefine the relationship between parents and caregivers These practices strive to provide parents with support during their infantrsquos illness by focusing on freely sharing information and on the collaboration between parents and hospital staff Family-centred care has been found to be associated with several beneficial outcomes including improved parental satisfaction increased parental comfort staff satisfaction and decreased parental stress18 Research is already examining these practices and questioning how these can be improved further Such research reflects the increasing effort focused on lsquohumanizingrsquo the environment in NICUs in order to make parents feel more comfortable about spending time with their infants
PaeDiaTrics anD cHilD HealTH 184 19
Conclusion
Surprisingly few interventions have prioritized the provision of emotional support for parents of sick neonates or accounted for the changing needs and wishes of parents over the course of their infantrsquos care Large-scale supportive education-based inter-ventions have been shown to be effective in reducing parental distress However the feasibility and sustainability of such pro-grammes should also be considered Programmes which require significant additional resources can be expensive and there are also issues of training and quality control Interventions which require significant input from parents may also place additional burdens on families making them potentially less accessible to those most at risk Arguably the aim should be to explore ways of providing acceptable and effective informational support which could be complemented by emotional support from health professionals and from other parents in the unit Increasingly studies are exploring the use of computers and multimedia as an engaging flexible and cost-effective method of targeting indi-vidual needs and providing support and information Such com-puter-based and interactive multimedia interventions have been found to be successful with a range of patient groups and could therefore be examined as a complementary method of providing informational support to families with sick neonates
REfEREnCEs
1 Glazebrook c Marlow n israel c et al randomised trial of a
parenting intervention during neonatal intensive care Arch Dis Child
Fetal Neonatal Ed 2007 92 F438ndash443
2 singer lT salvator a Guo s collin M lilien l Baley J Maternal
psychological distress and parenting stress after the birth of a very
low-birth-weight infant JAMA 1999 281 799ndash805
3 shaw rJ Deblois T ikuta l Ginzburg K Fleisher B Koopman c
acute stress disorder among parents of infants in the neonatal
intensive care nursery Psychosomatics 2006 47 206ndash212
4 Hopper a sources of stress for parents of a sick neonate a
literature review Pediatr Nurs 2000 30 29ndash32
5 Davis l edwards H Mohay H wollin J The impact of very
premature birth on the psychological health of mothers Early Hum
Dev 2003 73 61ndash70
6 Bernazzani O saucier J-F David H Borgeat F Psychosocial
predictors of depressive symptomatology level in postpartum
women J Affect Disord 1997 46 39ndash49
7 Field T infants of depressed mothers Infant Behav Dev 1995 18
1ndash13
8 Kaplan Ps Bachorowski J-a Zarlengo-strouse P child-directed
speech produced by mothers with symptoms of depression fails
to promote associative learning in 4-month-old infants Child Dev
1999 70 560ndash570
9 ward K Perceived needs of parents of critically ill infants in
a neonatal intensive care unit (nicU) Pediatr Nurs 2001 27
281ndash286
10 lai Hl chen cJ Peng Tc et al randomized controlled trial of music
during kangaroo care on maternal state anxiety and preterm infantsrsquo
responses Int J Nurs Stud 2006 43 139ndash146
8 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
11 Tallandini Ma scalembra c Kangaroo mother care and mother-
premature infant dyadic interaction Infant Ment Health J 2006 27
251ndash275
12 Ohgi s Fukuda M akiyama T Gima H effect of an early intervention
programme on low birthweight infants with cerebral injuries
J Paediatr Child Health 2004 40 689ndash695
13 Kaaresen Pi ronning Ja Ulvund se Dahl lB a randomized
controlled trial of the effectiveness of an early-intervention program
in reducing parenting stress after preterm birth Pediatrics 2006
118 e9ndash19
14 Melnyk BM Feinstein nF alpert-Gillis l et al reducing premature
infantsrsquo length of stay and improving parentsrsquo mental health
outcomes with the creating opportunities for parent empowerment
(cOPe) neonatal intensive care unit program a randomized
controlled trial Pediatrics 2006 118 e1414ndash1427
15 Jotzo M Poets cF Helping parents cope with the trauma of
premature birth an evaluation of a trauma-preventive psychological
intervention Pediatrics 2005 115 915ndash919
16 Pearson J andersen K evaluation of a program to promote positive
parenting in the neonatal intensive care unit Neonatal Netw 2001
20 43ndash48
17 roman l lindsay J Boger r et al Parent-to-parent support
initiated in the neonatal intensive care unit Res Nurs Health 1995
18 385ndash394
18 Meyer ec coll cTG lester BM Boukydis cFZ McDonough sM Oh w
Family-based intervention improves maternal psychological well-
being and feeding interaction of preterm infants Pediatrics 1994
93 241ndash246
PaeDiaTrics anD cHilD HealTH 184 19
19 Preyde M ardal F effectiveness of a parent ldquobuddyrdquo program for
mothers of very preterm infants in a neonatal intensive care unit
CMAJ 2003 168 969ndash973
20 Hurst i One size does not fit all Parentsrsquo evaluations of a support
program in a newborn intensive care nursery J Perinat Neonatal
Nurs 2006 20 252ndash261
Practice points
bull Parents of sick neonates experience significant distress and
exhibit higher levels of stress anxiety and depression than
parents of healthy infants
bull educational support emotional support and increased
motherndashinfant contact have been shown to promote maternal
well-being
bull emotional support for fathers has been largely neglected in
the research literature
bull Parents benefit from a choice of supportive facilities which
could include face-to-face sessions with health professionals
telephone support hospital visitation parent-to-parent
support and unit-based group support meetings
bull Parentsrsquo support needs can change during their infantrsquos
hospitalization and not all parents want or benefit from the
provision of additional information and emotional support in
the neonatal unit
9 copy 2008 elsevier ltd all rights reserved
Personal Practice
When should enteral feeds be started in preterm infantsnicholas D embleton
AbstractPaediatricians are regularly faced with the question of when best to start
enteral feeds in preterm infants this is important as longer term out-
come may be compromised by sub-optimal nutrition in early life clinical
factors that may affect the decision to start and the risk and benefits
are discussed
Keywords breast milk feeding nutrition parenteral nutrition
Key points in the history
Alice is lsquonutritionally vulnerablersquo and whilst this may not be immediately apparent it will affect her long term outcome Her energy stores are extremely limited and consist primarily of pro-tein She has less than 5 fat and little energy associated with stored glycogen She is losing about 1 gkgd protein equivalent so she needs at least that and a minimum of 50ndash60 kcalkg of energy just to maintain the status quo let alone grow
Her weight is on the 25th centile Review of any antenatal his-tory may reveal whether fetal growth was normal Fetal growth retardation can occur with a weight greater than 10th centile The presence of antenatal absent or reversed end diastolic flow in the umbilical artery indicates poor gut blood flow This increases the risk of necrotizing enterocolitis (NEC) and might suggest a more cautious approach to starting feeds1
She has no important cardiovascular problems but if she were hypotensive gut blood flow may be low There is no umbilical
Nicholas D Embleton BSC (Hons) MBBS (Hons) MD FRCPCH is Consultant in
Neonatal Medicine at Newcastle Neonatal Service Royal Victoria
Infirmary Newcastle upon Tyne NE1 4LP UK
Should you start feeds at a day of age
alice was born following spontaneous labour at 30 weeksrsquo
gestation she weighed 1300 g and is now 18 h old she was
briefly ventilated and then extubated to continuous positive
airway pressure 12 h ago in 35 oxygen she has had caffeine
citrate but still has intermittent episodes of self-correcting
apnoea she was commenced on iv 10 dextrose but this was
replaced by a parenteral amino acid solution (referred to as
lsquotPnrsquo) along with intralipid at 0900 this morning serum glucose
is 11 mmoll and blood pressure is 42 systolic
PaeDiatrics anD cHilD HealtH 184 20
arterial catheter in situ but there is no good evidence that this should delay the decision to start feeds Her glucose is high but this is quite common in a baby like this Could this be a sign of sepsis Caffeine does not affect the incidence of NEC2 The great-est risk factor for NEC in this case is prematurity
What else might be found on examination
Up until 24 h ago she was swallowing large amounts of amniotic fluid What will have changed since then
General examination should confirm peripheral perfusion lsquogestaltrsquo view (does she look lsquowellrsquo) and cardiovascular status lsquoBowel soundsrsquo are not usually helpful
The most important variable likely to affect gut perfusion is the arterial duct Precordial lsquoheaversquo and a loud murmur are sug-gestive but it is possible to have a significant ductal shunt in a baby with a normal examination Cardiac ultrasound will con-firm this diagnosis It might be better to treat a large shunt first with indometacin and to delay starting feeds for a further 24 h
It is not possible to assess gut perfusion clinically but normal perfusion elsewhere (adequate urine output usually indicates adequate renal perfusion) would be reassuring Most preterm babies have a few abdominal lsquoloopsrsquo visible but a distended abdomen with many palpable loops suggests ileus This might be secondary to sepsis or poor gut blood flow Preterm babies do not pass much meconium in the first 24ndash48 h
Balance of risks between starting and withholding feeds
Alice requires 35ndash4 gkgd of protein and 120 kcalkgd to grow3 This will initially be provided parenterally Delaying feeds increases the risk of gut villous atrophy and prolongs the need for lsquototal parenteral nutrition (TPN)rsquo TPN requires intravenous access and so increases the risk of sepsis and when prolonged use is required combined with the lack of enteral feeding may result in hepatic impairment
Delaying feeds may allow a gut that has been chronically under-perfused to re-establish more normal perfusion although normal gut endocrine function digestive enzyme upregulation and motility require a source of intraluminal nutrients1 A recent study suggested benefit from delaying the introduction of feeds4 but methodologi-cal problems exist5 Although a Cochrane meta-analysis suggested no benefit only two studies were included6 A large UK-based trial is examining the effect of early or late feeding in preterm infants who were born growth retarded following identification of antena-tal absent or reversed end diastolic flow in the umbilical artery7
When starting feeds what volume should be used
There are no good data to guide this decision We start with 24 mlkg (1 mlkgh) and then increase by this amount each day Most babies achieve full enteral feeds (ge150 mlkgd) by a week of age Feeding guidelines improve the outcome8 Measure-ment or assessment of gastric aspirates is not consistently useful in predicting subsequent feeding intolerance or development of NEC Aspirate volumes equivalent to or sometimes greater than the amount given in the preceding 1ndash2 h are usually normal Most aspirates have a greenish colour Thick bloody or intensely bile-stained aspirates require detailed assessment
0 copy 2008 elsevier ltd all rights reserved
Personal Practice
What else affects decisions and outcome
Feeding success is affected by sepsis and NEC Scrupulous atten-tion should be paid to hand washing and intravenous access and blood sampling should be minimized There is no good evidence to support the routine use of pro-kinetic agents or H2 blockers
The most important clinical intervention affecting the occur-rence of NEC is the use of breast milk9 All efforts should be directed at persuading parents of the benefits and supporting the process Some clinicians delay starting feeds for a further 24 h whilst expressed breast milk becomes available Donor breast milk might be equally efficacious10
RefeRenceS
1 Dorling J Kempley s leaf a Feeding growth restricted preterm
infants with abnormal antenatal Doppler results Arch Dis Child Fetal
Neonatal Ed 2005 90 F359ndash363
2 schmidt B roberts rs Davis P et al caffeine therapy for apnea of
prematurity N Engl J Med 2006 354 2112ndash2121
PaeDiatrics anD cHilD HealtH 184 20
3 embleton nD Pang n cooke rJ Postnatal malnutrition and growth
retardation an inevitable consequence of current recommendations
in preterm infants Pediatrics 2001 107 270ndash273
4 Berseth cl Bisquera Ja Paje VU Prolonging small feeding volumes
early in life decreases the incidence of necrotizing enterocolitis in
very low birth weight infants Pediatrics 2003 111 529ndash534
5 Menon G Boyle eM embleton nD et al introduction of enteral
feeds in preterm infants Pediatrics 2004 114 327ndash328
6 Kennedy Ka tyson Je chamnanvanikij s early versus delayed
initiation of progressive enteral feedings for parenterally fed low
birth weight or preterm infants Cochrane Database Syst Rev 2000
cD001970
7 wwwnpeuoxacukadept
8 Patole sK de Klerk n impact of standardised feeding regimens on
incidence of neonatal necrotising enterocolitis a systematic review
and meta-analysis of observational studies Arch Dis Child Fetal
Neonatal Ed 2005 90 F147ndash151
9 lucas a cole tJ Breast milk and neonatal necrotising enterocolitis
Lancet 1990 336 1519ndash1523
10 Boyd ca Quigley Ma Brocklehurst P Donor breast milk versus
infant formula for preterm infants systematic review and meta-
analysis Arch Dis Child Fetal Neonatal Ed 2007 92 F169ndash175
1 copy 2008 elsevier ltd all rights reserved
self-assessment
Case 1A term male infant born to consanguineous parents is assessed at 24 h of age due to poor feeding profuse yellow watery diar-rhoea and irritability He weighed 32 kg at birth and delivery was uneventful There was no polyhydramnios He has been breastfed since birth On examination he is pale with a non-tender but distended abdomen and reduced bowel sounds His weight is 275 kg and he looks dehydrated Examination is otherwise normal
Initial investigations (normal values in parentheses) showed
sodium 149 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 65 mmollitre (25ndash75)
creatinine 147 μmollitre (40ndash110)
chloride 119 mmollitre (95ndash105)
haemoglobin 172 gdl (140ndash200)
White blood cell count 80 times 109litre (100ndash260)
Platelet count 302 times 109litre (150ndash400)
arterial blood gas
ph 720 (730ndash745)
PcO2 23 kPa (46ndash60)
Bicarbonate 68 mmollitre (220ndash260)
Base excess minus186 mmollitre (minus20 to +20)
lactate 59 mmollitre (06ndash24)
An abdominal X-ray shows distended bowel loops with no intramural thickening or pneumoperitoneum (Figure 1)
He was given nil by mouth and received intravenous fluids and antibiotics His dehydration improved but the metabolic acidosis and diarrhoea persisted despite receiving no enteral feeds and the commencement of total parenteral nutrition Blood and stool cultures were negative
1 Which of the following best describes these results Choose ONE answer ONLY from the followingA Hypernatraemia hyperchloraemic metabolic acidosis
with increased anion gapB Hypernatraemia hyperchloraemic metabolic acidosis
with normal anion gap
Manish Sadarangani BM BCh MA MRCPCH is Clinical Research Fellow
at the Department of Paediatrics University of Oxford Centre for
Clinical Vaccinology and Tropical Medicine Churchill Hospital
Oxford OX3 7LJ UK
Shabna Rajapaksa MB BChir MA MRCPCH is Specialist Registrar in
Paediatrics at the Paediatric Intensive Care Unit John Radcliffe
Hospital Oxford OX3 9DU UK
Nicholas Mann MD FRCP FRCPCH DCH is Consultant Paediatrician at the
Department of Paediatrics Royal Berkshire Hospital Reading RG1
5AN UK
self-assessment
C Hypernatraemic dehydration and compensated metabolic acidosis
D Acute renal failureE Renal tubular acidosis
2 What is the likely diagnosis Choose ONE answer ONLY from the followingA Hirschsprung disease ndash long segmentB Cystic fibrosis with meconium ileusC Microvillus inclusion diseaseD Cowrsquos milk protein intoleranceE Lactose intolerance
3 What is the investigation of choice Choose ONE answer ONLY from the followingA Rectal biopsy with staining for acetylcholine receptorsB Immunoreactive trypsinC Gastrointestinal endoscopy and biopsyD Stool microscopy and cultureE Stool reducing substances
Case 2A 4-year-old boy presents with a 3 d history of jaundice and a florid rash He has had orange urine and there is no change in his stool colour His family originate from Kosovo and have lived in the UK for the last 8 years He has never left the UK There is no history of blood transfusion or sex-ual abuse The grandmother was recently diagnosed with hepatitis B
On examination he is well apyrexial and mildly jaundiced with cervical and axillary lymphadenopathy He has an exten-sive papular rash over the face extremities and trunk (Figure 2) There is 3 cm hepatomegaly with no splenomegaly or ascites Examination is otherwise normal
Figure 1 abdominal X-ray of baby
Paediatrics and child health 184 202 copy 2008 elsevier ltd all rights reserved
self-assessment
Initial investigations are as follows
haemoglobin 110 gdl (113ndash135)
White blood cell count 108 times 109litre (50ndash150)
Platelet count 278 times 109litre (150ndash400)
inr 10 (08ndash12)
aPt ratio 10 (08ndash13)
sodium 140 mmollitre (135ndash145)
Potassium 42 mmollitre (35ndash50)
Urea 56 mmollitre (25ndash75)
creatinine 65 μmollitre (45ndash120)
total bilirubin 66 μmollitre (0ndash15)
conjugated bilirubin 23 μmollitre (0ndash10)
alanine aminotransferase (alt) 2033 iUlitre (0ndash35)
alkaline phosphatase 987 iUlitre (71ndash234)
Gamma-glutamyl transferase (GGt) 870 iUlitre (0ndash51)
1 What is the name of this rash Choose ONE answer ONLY from the followingA Erythema multiformeB Erythema migransC GianottiminusCrosti syndromeD EczemaE Dermatitis herpetiformis
2 What is the most likely diagnosis Choose ONE Answer ONLY from the followingA Autoimmune hepatitisB Hepatitis BC Hepatitis DD Wilson diseaseE Alpha-1 antitrypsin deficiency
3 What is the best means of management Choose ONE answer ONLY from the followingA Isolation until the jaundice disappearsB ImmunosuppressionC Copper chelating agents and genetic counsellingD Patient and family education with consideration of
antiviral agentsE Liver transplantation
Case 3A 10-month-old boy presents with 3 weeks of vomiting and constipation ndash he is passing hard stools every 2ndash3 days He has fallen from the 9th to below the 04th centile in the last 6 weeks He passed meconium within the first 24 h of life On examina-tion he looks pale and there are some dysmorphic features ndash a short nose long philtrum and wide mouth He has normal heart sounds with a grade 3 ejection systolic murmur loudest at the upper right sternal edge Examination is otherwise normal
Initial investigations are as follows
haemoglobin 91 gdl (113ndash141)
total white blood cell count 124 times 109litre (60ndash170)
Platelet count 407 times 109litre (150ndash400)
sodium 144 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 78 mmollitre (25ndash75)
creatinine 78 μmollitre (45ndash120)
albumin 52 glitre (35ndash50)
corrected calcium 384 mmollitre (238ndash263)
Phosphate 167 mmollitre (099ndash157)
1 What is the most likely diagnosis Choose ONE answer ONLY from the followingA HyperparathyroidismB Acute leukaemiaC Williams syndromeD Hypervitaminosis DE Familial hypocalciuric hypercalcaemia
2 Which investigation would be most useful in establishing the diagnosis Choose ONE answer ONLY from the followingA Intact parathyroid hormone assayB Blood filmC Fluorescent in-situ hybridization for 7q1123 deletionD 25-hydroxyvitamin D assayE Urine calciumcreatinine ratio
3 Which of the following treatments would not be suitable for this patient Choose ONE answer ONLY from the followingA Low calcium dietB Normal saline infusionC FurosemideD CorticosteroidsE Bisphosphonates
Case 4A 10-week-old girl presents with a 2-day history of poor feed-ing Her mother has been concerned about weakness since birth She only has a flicker of movement in the arms none in the legs and has a weak cry She has been passing urine and opening her bowels normally She was born at full term by normal delivery and did not require any resuscitation at birth Normal fetal movements were felt antenatally and there was no polyhydramnios She is the first child of non- consanguineous parents and there is no significant family his-tory On examination she is alert and fixing and following appropriately She has a weak cry and a weak suck There is reduced central and peripheral tone with marked head lag
Figure 2 rash found on examination
Paediatrics and child health 184 203 copy 2008 elsevier ltd all rights reserved
self-assessment
Muscle power is grade 3 out of 5 in the arms and legs There is no muscle or tongue fasciculation and she has absent reflexes throughout The remainder of the examination is normal
Electromyogram shows irregular polyphasic motor unit potentials with marked instability consistent with a dener-vating and re-innervating process (Figure 3)
1 Which of the following additional investigations may be helpful Choose ONE answer ONLY from the followingA Nerve conduction studiesB Creatine kinase assayC Muscle biopsyD SMN1 gene analysisE All of the above
2 What is the most likely cause of this childrsquos symptoms Choose ONE answer ONLY from the followingA Congenital myotonic dystrophyB Duchenne muscular dystrophyC PraderminusWilli syndromeD Spinal muscular atrophyE Mitochondrial myopathy
3 What is the mode of inheritance of this disease Choose ONE answer ONLY from the followingA X-linked recessiveB Autosomal recessiveC Autosomal dominantD MitochondrialE Sporadic
Case 5A 13-year-old girl presents with a 3-week history of fever up to 40degC night sweats and headache She has a reduced appetite with some weight loss She has no other specific symptoms She was on holiday in China 7 months ago On examination she looks well and has a temperature of 387degC There is no lymphadenopathy and no rashes Examination is entirely normal
Results of investigations are as follows
haemoglobin 126 gdl (120ndash160)
total white blood cell count 132 times 109litre (43ndash108)
neutrophil count 115 times 109litre (25ndash75)
Platelet count 244 times 109litre (150ndash400)
Blood film neutrophilia with left shift
erythrocyte sedimentation rate 63 mmh (1ndash20)
c-reactive protein 219 mglitre (0ndash5)
Blood culture Streptococcus intermedius
from anaerobic bottle only
csf culture negative
Magnetic resonance imaging (MRI) of the brain shows acute frontal sinusitis with a large intracranial frontal extra-dural empyema (Figure 4)
1 Which of the following would be appropriate management Choose ONE answer ONLY from the followingA A 12-week course of intravenous antibioticsB Drainage of the frontal sinus followed by 2 weeks of
intravenous antibioticsC Drainage of the empyema followed by 2 weeks of
intravenous antibioticsD Drainage of the empyema and the frontal sinus
followed by 2 weeks of oral antibiotics
1151
1152
1153
1154
1155
1156
1157
1158
1159
1200
50ms 1mV
Figure 3 electromyogram recording from the patient Figure 4 Parasagittal section from mri scan of patient
Paediatrics and child health 184 204 copy 2008 elsevier ltd all rights reserved
self-assessment
E Drainage of the empyema and the frontal sinus followed by 8 weeks of intravenous antibiotics
2 Streptococcus intermedius is a potential pathogen in which of the following infections Choose ONE answer ONLY from the followingA Liver abscessB Urinary tract infectionC MeningitisD Thoracic empyemaE Pneumonia
3 Which of the following statements regarding lsquopyrexia of unknown originrsquo in children is false Choose ONE answer ONLY from the followingA Malignancy is the underlying pathology in 5ndash15 of
casesB An aetiology will be found in over 90 of casesC The most common cause is infectionD A rheumatological cause is found in 10ndash20 of casesE Familial Mediterranean fever can occur in children of
non-Mediterranean ethnicity
Answers
Case 11 AThe anion gap is a useful tool to differentiate the causes of a metabolic acidosis It is calculated by the equation
Anion gap = [Na K ] [Cl HCO ]3+ + minus minus+ minus +
It represents the effect of unmeasured anions on the plasma pH and is normally 10ndash18 mmollitre
2 CMicrovillus inclusion disease is a severe autosomal recessive enteropathy that is typically apparent within hours or days after birth It is the second most common cause of protracted diarrhoea in the newborn after infectious causes It is characterized by severe yellow watery diarrhoea and malabsorption due to hypoplasia andor atrophy of the villi of the small intestine secondary to an inherited defect in the brush border membrane This results in severe dehydration malnutrition and metabolic acidosis due to bicarbonate loss from the gut
3 CDiagnosis of microvillus inclusion disease is made on small bowel biopsy Electron microscopy findings are of intracellular brush border inclusions and densely packed apical cytoplasmic vesicular bodies indicating microvillous atrophy There is no cure Treatment is supportive with total parenteral nutrition and consideration of small bowel transplantation
Further reAding
Goulet O ruemmele f causes and management of intestinal failure
in children Gastroenterology 2006 130(suppl 1) s16ndash28
rhoads Jm Vogler rc lacey sr et al microvillus inclusion disease
In vitro jejunal electrolyte transport Gastroenterology 1991
100 811ndash817
Case 21 CGianottindashCrosti syndrome is a distinct self-limiting rash commonly associated with viral infections in children between 2 and 6 years of age It presents as multiple pink to redminusbrown papules or papulovesicles which may be pruritic and can become confluent Gianotti and Crosti initially described the exanthema as associated with hepatitis B virus and they termed it papular acrodermatitis of childhood It can occur in several viral diseases eg hepatitis A B and C coxsackie viruses and cytomegalovirus
2 BHepatitis is a syndrome characterized by inflammation or injury of liver cells which may develop into cell necrosis and subsequently fibrosis andor cirrhosis Biochemically there are raised liver enzymes The degree of transaminase elevation does not correlate with the severity of the disease process Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of viral hepatitis
3 DHepatitis B infection is transmitted via blood sexually or vertically Infection may be acute or chronic Diagnostic markers are the presence of surface antigen (HBsAg) and HBV DNA The presence of e antigen (HBeAg) indicates high infectivity Infected newborns have a 95 risk of becoming carriers this risk decreases with infection acquired later in childhood Approximately 15ndash25 of HBV carriers will die from cirrhosis or hepatocellular carcinoma Extrahepatic findings are more common in older children and include membranous glomerulonephritis and GianottiminusCrosti syndrome Fulminant hepatic failure occurs in severe cases resulting in persistent jaundice encephalopathy and coagulopathy Management includes counselling family members monitoring for ongoing liver disease and consideration of antiviral therapy
Further reAding
Brandt O abeck d Gianotti r Burgdorf W Gianotti crosti
syndrome J Am Acad Dermatol 2006 54 136ndash145
slowik mK Jhaveri r hepatitis B and c viruses in infants and
young children Semin Pediatr Infect Dis 2005 16 296ndash305
Case 31 CHypercalcaemia is uncommon in infancy The most common symptoms in this age group are irritability vomiting and constipation It may be a manifestation of Williams syndrome vitamin D or calcium excess as well as disorders associated with reduced bone formation such as hypophosphatasia or increased bone resorption such as malignancy Occasionally
Paediatrics and child health 184 205 copy 2008 elsevier ltd all rights reserved
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-
OccasiOnal review
Emotional support for families of sick neonatesMarina nicolaou
cristine Glazebrook
AbstractParents of sick neonates experience high levels of stress anxiety and
depression Most interventions with families of sick infants have focused
on fostering the motherndashinfant relationship through the provision of
information about infant developmental needs or through increased
motherndashinfant contact Many of these studies have reported improved
maternal well-being though there are some concerns about the scope
and practicality of large-scale interventions The few studies to have
prioritized emotional support for parents of sick neonates have pro-
duced encouraging results even interventions requiring relatively few re-
sources such as telephone support parent-to-parent support and group
support have been associated with reduced psychological morbidity for
parents The needs of parents can change throughout their infantrsquos hos-
pitalization and not all want or benefit from the provision of additional
support Thus neonatal intensive care units should aim to provide a
varied flexible and sustainable programme of support options Further
research should focus on the needs of fathers
Keywords mental health neonatal intensive care parents
The admission of an infant to neonatal care is acknowledged to be a source of considerable distress for families This review aims to explore evidence for the psychological impact on families of having an infant in neonatal intensive care and to identify evi-dence for the effectiveness of interventions to promote parental well-being It will conclude with recommendations for strategies to support parents of vulnerable infants and suggestions for fur-ther research
Psychological impact of neonatal care for parents
The majority of research examining the effect on parents of having a sick neonate has focused on families of premature or low birthweight infants Such research has found that parents with a sick neonate exhibit high levels of stress compared to normative samples and to parents of healthy full-term infants1 Singer et al2 examined the stress experienced by mothers of high-risk very low birthweight (VLBW) low-risk VLBW and term
Marina Nicolaou MPhil is a Teaching Assistant at the School of
Community Health Sciences University of Nottingham Nottingham UK
Cristine Glazebrook PhD is a Professor of Health Psychology at the School
of Community Health Sciences University of Nottingham Nottingham UK
PaeDiaTrics anD cHilD HealTH 184 196
infants Several self-report measures were used including the Brief Symptom Inventory the Parenting Stress Index (PSI) the Impact on Family Scale and the Family Inventory of Life Events and Changes (FILE) Mothers of VLBW infants had more psycho-logical distress at 1 month compared to mothers of term infants Mothers of high-risk VLBW infants also reported high psycho-logical distress at 2 years and high levels of parenting stress at 3 years Mothers have also been found to have higher stress levels compared to fathers Shaw et al3 examined the prevalence of acute stress disorder (ASD) in 40 parents whose infants were in the neonatal intensive care unit (NICU) Nearly half of the moth-ers (44) met the criteria for ASD although none of the fathers did Furthermore the severity of the symptoms (measured by the number of concurrent symptoms) was greater for the moth-ers than for the fathers3 The reasons behind this difference have been widely speculated with some believing that it is due to the mothersrsquo greater psychological involvement with the infant as evidenced by their general greater vulnerability to postpartum psychological disorder It could also reflect gender differences in coping style
Having an infant who requires intensive medical care repre-sents a significant emotional burden for families Not only is there extreme anxiety surrounding the infantrsquos health and distress for the childrsquos suffering there is also the unfamiliar and intimidating environment of the NICU to adjust to Hopper in her review of the literature identified sources of stress for parents of sick neo-nates as falling into three areas4 Situational factors included the severity of the infantrsquos illness and how parents adapted to the life crisis of having a sick infant Personal factors involved parental emotions about their roles and the instrumental and informa-tional support which were available to them The third area was classified as environmental sources of stress and included the environment of the NICU and the relationship between parents and members of staff This relationship has been examined by several studies in the nursing literature nurses are seen as ide-ally placed to provide the necessary support and information to parents with sick neonates However whilst some studies have shown that supportive and helpful hospital staff can have a posi-tive effect on parents other studies have highlighted the prob-lems and difficulties which can manifest It has been shown that parents and nurses often have very different ideas about issues eg the necessary skills and competencies needed in an NICU or the characteristics that make a lsquogood motherrsquo
Research has shown that there may be a relationship between high levels of parental stress and an increased likelihood of depression5 Postpartum depression is a psychiatric illness which appears in 10ndash15 of postpartum women Its reported preva-lence rates however have ranged from less than 10 up to 306 depending on the instruments used the population exam-ined and the timing of the research Several factors have been found to be associated with postpartum depression including poor social support and infant-related stressors6 Evidence indi-cates that postnatal depression may be underreported and this is of concern since the mental and psychological health of the mother can affect her relationship with her infant and thus the infantrsquos cognitive and emotional development5 Depressed moth-ers appear to look touch and talk to their infants less frequently and also appear to show fewer positive and more negative faces7 The vocalizations of mothers suffering with depression have also
copy 2008 elsevier ltd all rights reserved
OccasiOnal review
been found to be less effective at promoting cognitive growth and learning in infants8
If researchers are interested in finding ways of providing sup-port for families of sick neonates then they must listen to what such families perceive their needs to be in order to avoid increas-ing anxiety and distress Furthermore the provision of appropri-ate support be it emotional informational or social will enhance parental coping abilities increase self-esteem and reduce anxiety It should be noted though that the research conducted around these issues has often taken lsquosupport needsrsquo as being synony-mous with lsquoinformation needsrsquo Such studies have examined the type the amount and quality of information that parents receive and perceive themselves as needing but have not explored in equal depth the perceived emotional support needs of families who have a sick infant In addition the needs of parents may change throughout their infantrsquos illness Ward examined the per-ceived needs of 52 parents of infants in an NICU9 Parents rated the needs of their hospitalized infant as most important along with the need to be reassured Interestingly they ranked their support needs as least important This research was conducted during the first week of the infantsrsquo hospitalization however which would explain the preoccupation of the parents with the infantrsquos health These results demonstrate that if researchers want to find ways of providing emotional support to parents of sick neonates they must be prepared not only to listen to parents but also to be flexible enough to satisfy the parentsrsquo changing needs and expectations
Interventions aimed at supporting parents
Most interventions that been evaluated in controlled studies have focused on supporting the motherndashinfant relationship and provid-ing information on infant development Many of these interven-tions have included the aim of improving the parental emotional state and thus psychological outcomes such as stress or anxi-ety have been assessed However few studies appear to include fathers This means that strategies implemented to provide emo-tional support to families of sick neonates are often derived from interventions tailored for mothers even though fathers may have different emotional needs
A wide range of interventions with mothers and infants has been evaluated in the NICU Increasing motherndashinfant contact through kangaroo care has been found to reduce maternal anxiety1011 and educational programmes delivered to fami-lies in the NICU have also been associated with reduced emo-tional difficulties in parents12ndash14 Kaaresen and colleagues implemented an intervention which consisted of eight sessions before discharge and four home visits all by trained nurses The sample included 71 premature infants in the intervention group 69 premature infants in the control group and 74 infants in the full-term control group The randomized controlled trial found that the intervention reduced parenting stress in both mothers and fathers of premature infants compared to controls to a level equivalent to parents in the term control group13 At 6 months corrected age mothers of preterm infants who had not received the intervention had total PSI scores which were 17 points higher than the mothers of infants born at term (an effect size of 057) A similar study evaluated the efficacy of an educationalndashbehavioural programmendashCreating Opportunities for
PaeDiaTrics anD cHilD HealTH 184 19
Parent Empowerment (COPE) ndash through a randomized controlled trial with 260 families of premature infants14 COPE was a four-phase educationalndashbehavioural programme which began as early as 2ndash4 d after mothers had given birth and continued until 1 week after discharge from the NICU The programme consisted of audiotaped and written infant behaviour information along with photographs which focused on common behaviours and characteristics of premature infants It also included various par-ent activities in the form of a four-phase workbook which aimed to assist mothers in the implementation of the experimental infor-mation COPE was found significantly to reduce maternal stress in the NICU as well as maternal anxiety and depressive symptoms after hospitalization In contrast a cluster randomized trial of a parenting intervention delivered to mothers of very premature infants from soon after birth showed no benefits for parenting stress1 The authors hypothesized that the intervention had not been of sufficient intensity particularly in the weeks surrounding discharge Neonatal care presents a significant barrier to parent-ing in the early weeks following a very preterm birth and so inter-ventions which focus on the developmental needs of infants and the parentndashchild relationship should particularly aim to support parents as they take on the parenting role There was also concern that the intervention had failed to reach those most at risk
Since large-scale projects can be costly to implement and may often fail to reach the families in most need it may be wiser to focus on intervention programmes which are more practical and easier to implement within a neonatal care setting Research has shown that even interventions which are based on one-off meet-ings with parents of sick neonates can be effective Jotzo and Poets examined the effect of an intervention programme aimed at reducing the severity of traumatic responses as a result of giv-ing birth prematurely15 Their programme consisted of a one-off intervention meeting along with additional psychological help throughout the hospitalization of the infant The meeting cov-ered a variety of issues including a reconstruction of the events shortly before and after the infantrsquos birth relaxation techniques discussion of coping strategies available resources and social support and support during emotional outbursts The measures used included the Impact of Event Scale (IES) and the Peritrau-matic Dissociative Experience Questionnaire At discharge the mothers who received the intervention were found to have a significantly lower traumatic impact as a result of premature birth Furthermore fewer mothers in the intervention group showed symptoms of clinically significant psychological trauma at discharge compared to mothers in the control group (36 vs 76)15 The lsquoParents Circle Programrsquo is another intervention with a similar structure16 This consisted of a 90 min session for parents with the aim of enhancing the developing relationship between parents and infants and to offer parents support A total of 104 parents (59 mothers and 45 fathers) and 44 members of hospital staff were asked to evaluate the programme and their results were analysed using content analysis Families reported gaining perspective on their situation feeling supported becom-ing aware of cues and optimizing interactions and becoming aware of available resources Parents and staff alike felt that participating in the intervention helped parents overcome the difficulties associated with the early time of their infantrsquos hos-pitalization Additional studies have also found positive results with fairly minimal interventions including discussion groups
7 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
in the NICU music during kangaroo care and pairing mothers of sick neonates with trained mothers who had been through similar experiences
Parent support programmes
Parent support programmes (PSPs) which are based in NICUs can provide parents with the opportunity to talk to parents who have been in similar situations and also to discuss their emo-tions with professionals who can help them cope with their situa-tion111718 The parent-to-parent support programme for mothers of preterm infants evaluated by Preyde and Ardal included edu-cational parental support group meetings and individual par-ent-to-parent support (primarily telephone support)19 Measures used included the Parental Stressor Scale NICU the State and the Trait Anxiety Inventories and the Beck Depression Inven-tory After 4 months of participation mothers in the intervention group reported lower levels of stress state anxiety and depres-sion compared to control group mothers The authors speculated however that the participants who were able to meet face to face with other parents were those who benefited the most Hurst conducted a comprehensive survey of an NICU-based PSP This PSP was provided in a variety of formats including a weekly parent support group hospital visitation and 24-h telephone sup-port20 Of the 477 participants 303 families used the PSP dur-ing a 2-year evaluation period with 78 using only one form of support and 18 using two forms Of a sub-sample of 48 parents asked to complete an evaluation of the PSP 92 stated that they would recommend such a programme to other parents Furthermore the majority of parents felt that it made them feel supported and helped them deal with their emotions20 This is an indication that such programmes can be very successful in sup-porting parents throughout their infantrsquos hospitalization It also shows that it can be beneficial to give parents several options and formats when it comes to such support services It is impor-tant to consider though that both the Hurst and the Preyde and Ardal studies found that some participants did not find the sup-port programmes helpful even reporting that they had caused them increased stress and anxiety Therefore it should not be assumed that support programmes will suit every individual and will provide the required support for all parents1920 NICUs need to be flexible enough to provide parents with a range of forms of support to choose from
The increased understanding of the strains that parents of sick neonates have to deal with has also led to efforts to improve customary practices in NICUs Family-centred care focuses on infants and their needs and attempts to redefine the relationship between parents and caregivers These practices strive to provide parents with support during their infantrsquos illness by focusing on freely sharing information and on the collaboration between parents and hospital staff Family-centred care has been found to be associated with several beneficial outcomes including improved parental satisfaction increased parental comfort staff satisfaction and decreased parental stress18 Research is already examining these practices and questioning how these can be improved further Such research reflects the increasing effort focused on lsquohumanizingrsquo the environment in NICUs in order to make parents feel more comfortable about spending time with their infants
PaeDiaTrics anD cHilD HealTH 184 19
Conclusion
Surprisingly few interventions have prioritized the provision of emotional support for parents of sick neonates or accounted for the changing needs and wishes of parents over the course of their infantrsquos care Large-scale supportive education-based inter-ventions have been shown to be effective in reducing parental distress However the feasibility and sustainability of such pro-grammes should also be considered Programmes which require significant additional resources can be expensive and there are also issues of training and quality control Interventions which require significant input from parents may also place additional burdens on families making them potentially less accessible to those most at risk Arguably the aim should be to explore ways of providing acceptable and effective informational support which could be complemented by emotional support from health professionals and from other parents in the unit Increasingly studies are exploring the use of computers and multimedia as an engaging flexible and cost-effective method of targeting indi-vidual needs and providing support and information Such com-puter-based and interactive multimedia interventions have been found to be successful with a range of patient groups and could therefore be examined as a complementary method of providing informational support to families with sick neonates
REfEREnCEs
1 Glazebrook c Marlow n israel c et al randomised trial of a
parenting intervention during neonatal intensive care Arch Dis Child
Fetal Neonatal Ed 2007 92 F438ndash443
2 singer lT salvator a Guo s collin M lilien l Baley J Maternal
psychological distress and parenting stress after the birth of a very
low-birth-weight infant JAMA 1999 281 799ndash805
3 shaw rJ Deblois T ikuta l Ginzburg K Fleisher B Koopman c
acute stress disorder among parents of infants in the neonatal
intensive care nursery Psychosomatics 2006 47 206ndash212
4 Hopper a sources of stress for parents of a sick neonate a
literature review Pediatr Nurs 2000 30 29ndash32
5 Davis l edwards H Mohay H wollin J The impact of very
premature birth on the psychological health of mothers Early Hum
Dev 2003 73 61ndash70
6 Bernazzani O saucier J-F David H Borgeat F Psychosocial
predictors of depressive symptomatology level in postpartum
women J Affect Disord 1997 46 39ndash49
7 Field T infants of depressed mothers Infant Behav Dev 1995 18
1ndash13
8 Kaplan Ps Bachorowski J-a Zarlengo-strouse P child-directed
speech produced by mothers with symptoms of depression fails
to promote associative learning in 4-month-old infants Child Dev
1999 70 560ndash570
9 ward K Perceived needs of parents of critically ill infants in
a neonatal intensive care unit (nicU) Pediatr Nurs 2001 27
281ndash286
10 lai Hl chen cJ Peng Tc et al randomized controlled trial of music
during kangaroo care on maternal state anxiety and preterm infantsrsquo
responses Int J Nurs Stud 2006 43 139ndash146
8 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
11 Tallandini Ma scalembra c Kangaroo mother care and mother-
premature infant dyadic interaction Infant Ment Health J 2006 27
251ndash275
12 Ohgi s Fukuda M akiyama T Gima H effect of an early intervention
programme on low birthweight infants with cerebral injuries
J Paediatr Child Health 2004 40 689ndash695
13 Kaaresen Pi ronning Ja Ulvund se Dahl lB a randomized
controlled trial of the effectiveness of an early-intervention program
in reducing parenting stress after preterm birth Pediatrics 2006
118 e9ndash19
14 Melnyk BM Feinstein nF alpert-Gillis l et al reducing premature
infantsrsquo length of stay and improving parentsrsquo mental health
outcomes with the creating opportunities for parent empowerment
(cOPe) neonatal intensive care unit program a randomized
controlled trial Pediatrics 2006 118 e1414ndash1427
15 Jotzo M Poets cF Helping parents cope with the trauma of
premature birth an evaluation of a trauma-preventive psychological
intervention Pediatrics 2005 115 915ndash919
16 Pearson J andersen K evaluation of a program to promote positive
parenting in the neonatal intensive care unit Neonatal Netw 2001
20 43ndash48
17 roman l lindsay J Boger r et al Parent-to-parent support
initiated in the neonatal intensive care unit Res Nurs Health 1995
18 385ndash394
18 Meyer ec coll cTG lester BM Boukydis cFZ McDonough sM Oh w
Family-based intervention improves maternal psychological well-
being and feeding interaction of preterm infants Pediatrics 1994
93 241ndash246
PaeDiaTrics anD cHilD HealTH 184 19
19 Preyde M ardal F effectiveness of a parent ldquobuddyrdquo program for
mothers of very preterm infants in a neonatal intensive care unit
CMAJ 2003 168 969ndash973
20 Hurst i One size does not fit all Parentsrsquo evaluations of a support
program in a newborn intensive care nursery J Perinat Neonatal
Nurs 2006 20 252ndash261
Practice points
bull Parents of sick neonates experience significant distress and
exhibit higher levels of stress anxiety and depression than
parents of healthy infants
bull educational support emotional support and increased
motherndashinfant contact have been shown to promote maternal
well-being
bull emotional support for fathers has been largely neglected in
the research literature
bull Parents benefit from a choice of supportive facilities which
could include face-to-face sessions with health professionals
telephone support hospital visitation parent-to-parent
support and unit-based group support meetings
bull Parentsrsquo support needs can change during their infantrsquos
hospitalization and not all parents want or benefit from the
provision of additional information and emotional support in
the neonatal unit
9 copy 2008 elsevier ltd all rights reserved
Personal Practice
When should enteral feeds be started in preterm infantsnicholas D embleton
AbstractPaediatricians are regularly faced with the question of when best to start
enteral feeds in preterm infants this is important as longer term out-
come may be compromised by sub-optimal nutrition in early life clinical
factors that may affect the decision to start and the risk and benefits
are discussed
Keywords breast milk feeding nutrition parenteral nutrition
Key points in the history
Alice is lsquonutritionally vulnerablersquo and whilst this may not be immediately apparent it will affect her long term outcome Her energy stores are extremely limited and consist primarily of pro-tein She has less than 5 fat and little energy associated with stored glycogen She is losing about 1 gkgd protein equivalent so she needs at least that and a minimum of 50ndash60 kcalkg of energy just to maintain the status quo let alone grow
Her weight is on the 25th centile Review of any antenatal his-tory may reveal whether fetal growth was normal Fetal growth retardation can occur with a weight greater than 10th centile The presence of antenatal absent or reversed end diastolic flow in the umbilical artery indicates poor gut blood flow This increases the risk of necrotizing enterocolitis (NEC) and might suggest a more cautious approach to starting feeds1
She has no important cardiovascular problems but if she were hypotensive gut blood flow may be low There is no umbilical
Nicholas D Embleton BSC (Hons) MBBS (Hons) MD FRCPCH is Consultant in
Neonatal Medicine at Newcastle Neonatal Service Royal Victoria
Infirmary Newcastle upon Tyne NE1 4LP UK
Should you start feeds at a day of age
alice was born following spontaneous labour at 30 weeksrsquo
gestation she weighed 1300 g and is now 18 h old she was
briefly ventilated and then extubated to continuous positive
airway pressure 12 h ago in 35 oxygen she has had caffeine
citrate but still has intermittent episodes of self-correcting
apnoea she was commenced on iv 10 dextrose but this was
replaced by a parenteral amino acid solution (referred to as
lsquotPnrsquo) along with intralipid at 0900 this morning serum glucose
is 11 mmoll and blood pressure is 42 systolic
PaeDiatrics anD cHilD HealtH 184 20
arterial catheter in situ but there is no good evidence that this should delay the decision to start feeds Her glucose is high but this is quite common in a baby like this Could this be a sign of sepsis Caffeine does not affect the incidence of NEC2 The great-est risk factor for NEC in this case is prematurity
What else might be found on examination
Up until 24 h ago she was swallowing large amounts of amniotic fluid What will have changed since then
General examination should confirm peripheral perfusion lsquogestaltrsquo view (does she look lsquowellrsquo) and cardiovascular status lsquoBowel soundsrsquo are not usually helpful
The most important variable likely to affect gut perfusion is the arterial duct Precordial lsquoheaversquo and a loud murmur are sug-gestive but it is possible to have a significant ductal shunt in a baby with a normal examination Cardiac ultrasound will con-firm this diagnosis It might be better to treat a large shunt first with indometacin and to delay starting feeds for a further 24 h
It is not possible to assess gut perfusion clinically but normal perfusion elsewhere (adequate urine output usually indicates adequate renal perfusion) would be reassuring Most preterm babies have a few abdominal lsquoloopsrsquo visible but a distended abdomen with many palpable loops suggests ileus This might be secondary to sepsis or poor gut blood flow Preterm babies do not pass much meconium in the first 24ndash48 h
Balance of risks between starting and withholding feeds
Alice requires 35ndash4 gkgd of protein and 120 kcalkgd to grow3 This will initially be provided parenterally Delaying feeds increases the risk of gut villous atrophy and prolongs the need for lsquototal parenteral nutrition (TPN)rsquo TPN requires intravenous access and so increases the risk of sepsis and when prolonged use is required combined with the lack of enteral feeding may result in hepatic impairment
Delaying feeds may allow a gut that has been chronically under-perfused to re-establish more normal perfusion although normal gut endocrine function digestive enzyme upregulation and motility require a source of intraluminal nutrients1 A recent study suggested benefit from delaying the introduction of feeds4 but methodologi-cal problems exist5 Although a Cochrane meta-analysis suggested no benefit only two studies were included6 A large UK-based trial is examining the effect of early or late feeding in preterm infants who were born growth retarded following identification of antena-tal absent or reversed end diastolic flow in the umbilical artery7
When starting feeds what volume should be used
There are no good data to guide this decision We start with 24 mlkg (1 mlkgh) and then increase by this amount each day Most babies achieve full enteral feeds (ge150 mlkgd) by a week of age Feeding guidelines improve the outcome8 Measure-ment or assessment of gastric aspirates is not consistently useful in predicting subsequent feeding intolerance or development of NEC Aspirate volumes equivalent to or sometimes greater than the amount given in the preceding 1ndash2 h are usually normal Most aspirates have a greenish colour Thick bloody or intensely bile-stained aspirates require detailed assessment
0 copy 2008 elsevier ltd all rights reserved
Personal Practice
What else affects decisions and outcome
Feeding success is affected by sepsis and NEC Scrupulous atten-tion should be paid to hand washing and intravenous access and blood sampling should be minimized There is no good evidence to support the routine use of pro-kinetic agents or H2 blockers
The most important clinical intervention affecting the occur-rence of NEC is the use of breast milk9 All efforts should be directed at persuading parents of the benefits and supporting the process Some clinicians delay starting feeds for a further 24 h whilst expressed breast milk becomes available Donor breast milk might be equally efficacious10
RefeRenceS
1 Dorling J Kempley s leaf a Feeding growth restricted preterm
infants with abnormal antenatal Doppler results Arch Dis Child Fetal
Neonatal Ed 2005 90 F359ndash363
2 schmidt B roberts rs Davis P et al caffeine therapy for apnea of
prematurity N Engl J Med 2006 354 2112ndash2121
PaeDiatrics anD cHilD HealtH 184 20
3 embleton nD Pang n cooke rJ Postnatal malnutrition and growth
retardation an inevitable consequence of current recommendations
in preterm infants Pediatrics 2001 107 270ndash273
4 Berseth cl Bisquera Ja Paje VU Prolonging small feeding volumes
early in life decreases the incidence of necrotizing enterocolitis in
very low birth weight infants Pediatrics 2003 111 529ndash534
5 Menon G Boyle eM embleton nD et al introduction of enteral
feeds in preterm infants Pediatrics 2004 114 327ndash328
6 Kennedy Ka tyson Je chamnanvanikij s early versus delayed
initiation of progressive enteral feedings for parenterally fed low
birth weight or preterm infants Cochrane Database Syst Rev 2000
cD001970
7 wwwnpeuoxacukadept
8 Patole sK de Klerk n impact of standardised feeding regimens on
incidence of neonatal necrotising enterocolitis a systematic review
and meta-analysis of observational studies Arch Dis Child Fetal
Neonatal Ed 2005 90 F147ndash151
9 lucas a cole tJ Breast milk and neonatal necrotising enterocolitis
Lancet 1990 336 1519ndash1523
10 Boyd ca Quigley Ma Brocklehurst P Donor breast milk versus
infant formula for preterm infants systematic review and meta-
analysis Arch Dis Child Fetal Neonatal Ed 2007 92 F169ndash175
1 copy 2008 elsevier ltd all rights reserved
self-assessment
Case 1A term male infant born to consanguineous parents is assessed at 24 h of age due to poor feeding profuse yellow watery diar-rhoea and irritability He weighed 32 kg at birth and delivery was uneventful There was no polyhydramnios He has been breastfed since birth On examination he is pale with a non-tender but distended abdomen and reduced bowel sounds His weight is 275 kg and he looks dehydrated Examination is otherwise normal
Initial investigations (normal values in parentheses) showed
sodium 149 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 65 mmollitre (25ndash75)
creatinine 147 μmollitre (40ndash110)
chloride 119 mmollitre (95ndash105)
haemoglobin 172 gdl (140ndash200)
White blood cell count 80 times 109litre (100ndash260)
Platelet count 302 times 109litre (150ndash400)
arterial blood gas
ph 720 (730ndash745)
PcO2 23 kPa (46ndash60)
Bicarbonate 68 mmollitre (220ndash260)
Base excess minus186 mmollitre (minus20 to +20)
lactate 59 mmollitre (06ndash24)
An abdominal X-ray shows distended bowel loops with no intramural thickening or pneumoperitoneum (Figure 1)
He was given nil by mouth and received intravenous fluids and antibiotics His dehydration improved but the metabolic acidosis and diarrhoea persisted despite receiving no enteral feeds and the commencement of total parenteral nutrition Blood and stool cultures were negative
1 Which of the following best describes these results Choose ONE answer ONLY from the followingA Hypernatraemia hyperchloraemic metabolic acidosis
with increased anion gapB Hypernatraemia hyperchloraemic metabolic acidosis
with normal anion gap
Manish Sadarangani BM BCh MA MRCPCH is Clinical Research Fellow
at the Department of Paediatrics University of Oxford Centre for
Clinical Vaccinology and Tropical Medicine Churchill Hospital
Oxford OX3 7LJ UK
Shabna Rajapaksa MB BChir MA MRCPCH is Specialist Registrar in
Paediatrics at the Paediatric Intensive Care Unit John Radcliffe
Hospital Oxford OX3 9DU UK
Nicholas Mann MD FRCP FRCPCH DCH is Consultant Paediatrician at the
Department of Paediatrics Royal Berkshire Hospital Reading RG1
5AN UK
self-assessment
C Hypernatraemic dehydration and compensated metabolic acidosis
D Acute renal failureE Renal tubular acidosis
2 What is the likely diagnosis Choose ONE answer ONLY from the followingA Hirschsprung disease ndash long segmentB Cystic fibrosis with meconium ileusC Microvillus inclusion diseaseD Cowrsquos milk protein intoleranceE Lactose intolerance
3 What is the investigation of choice Choose ONE answer ONLY from the followingA Rectal biopsy with staining for acetylcholine receptorsB Immunoreactive trypsinC Gastrointestinal endoscopy and biopsyD Stool microscopy and cultureE Stool reducing substances
Case 2A 4-year-old boy presents with a 3 d history of jaundice and a florid rash He has had orange urine and there is no change in his stool colour His family originate from Kosovo and have lived in the UK for the last 8 years He has never left the UK There is no history of blood transfusion or sex-ual abuse The grandmother was recently diagnosed with hepatitis B
On examination he is well apyrexial and mildly jaundiced with cervical and axillary lymphadenopathy He has an exten-sive papular rash over the face extremities and trunk (Figure 2) There is 3 cm hepatomegaly with no splenomegaly or ascites Examination is otherwise normal
Figure 1 abdominal X-ray of baby
Paediatrics and child health 184 202 copy 2008 elsevier ltd all rights reserved
self-assessment
Initial investigations are as follows
haemoglobin 110 gdl (113ndash135)
White blood cell count 108 times 109litre (50ndash150)
Platelet count 278 times 109litre (150ndash400)
inr 10 (08ndash12)
aPt ratio 10 (08ndash13)
sodium 140 mmollitre (135ndash145)
Potassium 42 mmollitre (35ndash50)
Urea 56 mmollitre (25ndash75)
creatinine 65 μmollitre (45ndash120)
total bilirubin 66 μmollitre (0ndash15)
conjugated bilirubin 23 μmollitre (0ndash10)
alanine aminotransferase (alt) 2033 iUlitre (0ndash35)
alkaline phosphatase 987 iUlitre (71ndash234)
Gamma-glutamyl transferase (GGt) 870 iUlitre (0ndash51)
1 What is the name of this rash Choose ONE answer ONLY from the followingA Erythema multiformeB Erythema migransC GianottiminusCrosti syndromeD EczemaE Dermatitis herpetiformis
2 What is the most likely diagnosis Choose ONE Answer ONLY from the followingA Autoimmune hepatitisB Hepatitis BC Hepatitis DD Wilson diseaseE Alpha-1 antitrypsin deficiency
3 What is the best means of management Choose ONE answer ONLY from the followingA Isolation until the jaundice disappearsB ImmunosuppressionC Copper chelating agents and genetic counsellingD Patient and family education with consideration of
antiviral agentsE Liver transplantation
Case 3A 10-month-old boy presents with 3 weeks of vomiting and constipation ndash he is passing hard stools every 2ndash3 days He has fallen from the 9th to below the 04th centile in the last 6 weeks He passed meconium within the first 24 h of life On examina-tion he looks pale and there are some dysmorphic features ndash a short nose long philtrum and wide mouth He has normal heart sounds with a grade 3 ejection systolic murmur loudest at the upper right sternal edge Examination is otherwise normal
Initial investigations are as follows
haemoglobin 91 gdl (113ndash141)
total white blood cell count 124 times 109litre (60ndash170)
Platelet count 407 times 109litre (150ndash400)
sodium 144 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 78 mmollitre (25ndash75)
creatinine 78 μmollitre (45ndash120)
albumin 52 glitre (35ndash50)
corrected calcium 384 mmollitre (238ndash263)
Phosphate 167 mmollitre (099ndash157)
1 What is the most likely diagnosis Choose ONE answer ONLY from the followingA HyperparathyroidismB Acute leukaemiaC Williams syndromeD Hypervitaminosis DE Familial hypocalciuric hypercalcaemia
2 Which investigation would be most useful in establishing the diagnosis Choose ONE answer ONLY from the followingA Intact parathyroid hormone assayB Blood filmC Fluorescent in-situ hybridization for 7q1123 deletionD 25-hydroxyvitamin D assayE Urine calciumcreatinine ratio
3 Which of the following treatments would not be suitable for this patient Choose ONE answer ONLY from the followingA Low calcium dietB Normal saline infusionC FurosemideD CorticosteroidsE Bisphosphonates
Case 4A 10-week-old girl presents with a 2-day history of poor feed-ing Her mother has been concerned about weakness since birth She only has a flicker of movement in the arms none in the legs and has a weak cry She has been passing urine and opening her bowels normally She was born at full term by normal delivery and did not require any resuscitation at birth Normal fetal movements were felt antenatally and there was no polyhydramnios She is the first child of non- consanguineous parents and there is no significant family his-tory On examination she is alert and fixing and following appropriately She has a weak cry and a weak suck There is reduced central and peripheral tone with marked head lag
Figure 2 rash found on examination
Paediatrics and child health 184 203 copy 2008 elsevier ltd all rights reserved
self-assessment
Muscle power is grade 3 out of 5 in the arms and legs There is no muscle or tongue fasciculation and she has absent reflexes throughout The remainder of the examination is normal
Electromyogram shows irregular polyphasic motor unit potentials with marked instability consistent with a dener-vating and re-innervating process (Figure 3)
1 Which of the following additional investigations may be helpful Choose ONE answer ONLY from the followingA Nerve conduction studiesB Creatine kinase assayC Muscle biopsyD SMN1 gene analysisE All of the above
2 What is the most likely cause of this childrsquos symptoms Choose ONE answer ONLY from the followingA Congenital myotonic dystrophyB Duchenne muscular dystrophyC PraderminusWilli syndromeD Spinal muscular atrophyE Mitochondrial myopathy
3 What is the mode of inheritance of this disease Choose ONE answer ONLY from the followingA X-linked recessiveB Autosomal recessiveC Autosomal dominantD MitochondrialE Sporadic
Case 5A 13-year-old girl presents with a 3-week history of fever up to 40degC night sweats and headache She has a reduced appetite with some weight loss She has no other specific symptoms She was on holiday in China 7 months ago On examination she looks well and has a temperature of 387degC There is no lymphadenopathy and no rashes Examination is entirely normal
Results of investigations are as follows
haemoglobin 126 gdl (120ndash160)
total white blood cell count 132 times 109litre (43ndash108)
neutrophil count 115 times 109litre (25ndash75)
Platelet count 244 times 109litre (150ndash400)
Blood film neutrophilia with left shift
erythrocyte sedimentation rate 63 mmh (1ndash20)
c-reactive protein 219 mglitre (0ndash5)
Blood culture Streptococcus intermedius
from anaerobic bottle only
csf culture negative
Magnetic resonance imaging (MRI) of the brain shows acute frontal sinusitis with a large intracranial frontal extra-dural empyema (Figure 4)
1 Which of the following would be appropriate management Choose ONE answer ONLY from the followingA A 12-week course of intravenous antibioticsB Drainage of the frontal sinus followed by 2 weeks of
intravenous antibioticsC Drainage of the empyema followed by 2 weeks of
intravenous antibioticsD Drainage of the empyema and the frontal sinus
followed by 2 weeks of oral antibiotics
1151
1152
1153
1154
1155
1156
1157
1158
1159
1200
50ms 1mV
Figure 3 electromyogram recording from the patient Figure 4 Parasagittal section from mri scan of patient
Paediatrics and child health 184 204 copy 2008 elsevier ltd all rights reserved
self-assessment
E Drainage of the empyema and the frontal sinus followed by 8 weeks of intravenous antibiotics
2 Streptococcus intermedius is a potential pathogen in which of the following infections Choose ONE answer ONLY from the followingA Liver abscessB Urinary tract infectionC MeningitisD Thoracic empyemaE Pneumonia
3 Which of the following statements regarding lsquopyrexia of unknown originrsquo in children is false Choose ONE answer ONLY from the followingA Malignancy is the underlying pathology in 5ndash15 of
casesB An aetiology will be found in over 90 of casesC The most common cause is infectionD A rheumatological cause is found in 10ndash20 of casesE Familial Mediterranean fever can occur in children of
non-Mediterranean ethnicity
Answers
Case 11 AThe anion gap is a useful tool to differentiate the causes of a metabolic acidosis It is calculated by the equation
Anion gap = [Na K ] [Cl HCO ]3+ + minus minus+ minus +
It represents the effect of unmeasured anions on the plasma pH and is normally 10ndash18 mmollitre
2 CMicrovillus inclusion disease is a severe autosomal recessive enteropathy that is typically apparent within hours or days after birth It is the second most common cause of protracted diarrhoea in the newborn after infectious causes It is characterized by severe yellow watery diarrhoea and malabsorption due to hypoplasia andor atrophy of the villi of the small intestine secondary to an inherited defect in the brush border membrane This results in severe dehydration malnutrition and metabolic acidosis due to bicarbonate loss from the gut
3 CDiagnosis of microvillus inclusion disease is made on small bowel biopsy Electron microscopy findings are of intracellular brush border inclusions and densely packed apical cytoplasmic vesicular bodies indicating microvillous atrophy There is no cure Treatment is supportive with total parenteral nutrition and consideration of small bowel transplantation
Further reAding
Goulet O ruemmele f causes and management of intestinal failure
in children Gastroenterology 2006 130(suppl 1) s16ndash28
rhoads Jm Vogler rc lacey sr et al microvillus inclusion disease
In vitro jejunal electrolyte transport Gastroenterology 1991
100 811ndash817
Case 21 CGianottindashCrosti syndrome is a distinct self-limiting rash commonly associated with viral infections in children between 2 and 6 years of age It presents as multiple pink to redminusbrown papules or papulovesicles which may be pruritic and can become confluent Gianotti and Crosti initially described the exanthema as associated with hepatitis B virus and they termed it papular acrodermatitis of childhood It can occur in several viral diseases eg hepatitis A B and C coxsackie viruses and cytomegalovirus
2 BHepatitis is a syndrome characterized by inflammation or injury of liver cells which may develop into cell necrosis and subsequently fibrosis andor cirrhosis Biochemically there are raised liver enzymes The degree of transaminase elevation does not correlate with the severity of the disease process Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of viral hepatitis
3 DHepatitis B infection is transmitted via blood sexually or vertically Infection may be acute or chronic Diagnostic markers are the presence of surface antigen (HBsAg) and HBV DNA The presence of e antigen (HBeAg) indicates high infectivity Infected newborns have a 95 risk of becoming carriers this risk decreases with infection acquired later in childhood Approximately 15ndash25 of HBV carriers will die from cirrhosis or hepatocellular carcinoma Extrahepatic findings are more common in older children and include membranous glomerulonephritis and GianottiminusCrosti syndrome Fulminant hepatic failure occurs in severe cases resulting in persistent jaundice encephalopathy and coagulopathy Management includes counselling family members monitoring for ongoing liver disease and consideration of antiviral therapy
Further reAding
Brandt O abeck d Gianotti r Burgdorf W Gianotti crosti
syndrome J Am Acad Dermatol 2006 54 136ndash145
slowik mK Jhaveri r hepatitis B and c viruses in infants and
young children Semin Pediatr Infect Dis 2005 16 296ndash305
Case 31 CHypercalcaemia is uncommon in infancy The most common symptoms in this age group are irritability vomiting and constipation It may be a manifestation of Williams syndrome vitamin D or calcium excess as well as disorders associated with reduced bone formation such as hypophosphatasia or increased bone resorption such as malignancy Occasionally
Paediatrics and child health 184 205 copy 2008 elsevier ltd all rights reserved
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-
OccasiOnal review
been found to be less effective at promoting cognitive growth and learning in infants8
If researchers are interested in finding ways of providing sup-port for families of sick neonates then they must listen to what such families perceive their needs to be in order to avoid increas-ing anxiety and distress Furthermore the provision of appropri-ate support be it emotional informational or social will enhance parental coping abilities increase self-esteem and reduce anxiety It should be noted though that the research conducted around these issues has often taken lsquosupport needsrsquo as being synony-mous with lsquoinformation needsrsquo Such studies have examined the type the amount and quality of information that parents receive and perceive themselves as needing but have not explored in equal depth the perceived emotional support needs of families who have a sick infant In addition the needs of parents may change throughout their infantrsquos illness Ward examined the per-ceived needs of 52 parents of infants in an NICU9 Parents rated the needs of their hospitalized infant as most important along with the need to be reassured Interestingly they ranked their support needs as least important This research was conducted during the first week of the infantsrsquo hospitalization however which would explain the preoccupation of the parents with the infantrsquos health These results demonstrate that if researchers want to find ways of providing emotional support to parents of sick neonates they must be prepared not only to listen to parents but also to be flexible enough to satisfy the parentsrsquo changing needs and expectations
Interventions aimed at supporting parents
Most interventions that been evaluated in controlled studies have focused on supporting the motherndashinfant relationship and provid-ing information on infant development Many of these interven-tions have included the aim of improving the parental emotional state and thus psychological outcomes such as stress or anxi-ety have been assessed However few studies appear to include fathers This means that strategies implemented to provide emo-tional support to families of sick neonates are often derived from interventions tailored for mothers even though fathers may have different emotional needs
A wide range of interventions with mothers and infants has been evaluated in the NICU Increasing motherndashinfant contact through kangaroo care has been found to reduce maternal anxiety1011 and educational programmes delivered to fami-lies in the NICU have also been associated with reduced emo-tional difficulties in parents12ndash14 Kaaresen and colleagues implemented an intervention which consisted of eight sessions before discharge and four home visits all by trained nurses The sample included 71 premature infants in the intervention group 69 premature infants in the control group and 74 infants in the full-term control group The randomized controlled trial found that the intervention reduced parenting stress in both mothers and fathers of premature infants compared to controls to a level equivalent to parents in the term control group13 At 6 months corrected age mothers of preterm infants who had not received the intervention had total PSI scores which were 17 points higher than the mothers of infants born at term (an effect size of 057) A similar study evaluated the efficacy of an educationalndashbehavioural programmendashCreating Opportunities for
PaeDiaTrics anD cHilD HealTH 184 19
Parent Empowerment (COPE) ndash through a randomized controlled trial with 260 families of premature infants14 COPE was a four-phase educationalndashbehavioural programme which began as early as 2ndash4 d after mothers had given birth and continued until 1 week after discharge from the NICU The programme consisted of audiotaped and written infant behaviour information along with photographs which focused on common behaviours and characteristics of premature infants It also included various par-ent activities in the form of a four-phase workbook which aimed to assist mothers in the implementation of the experimental infor-mation COPE was found significantly to reduce maternal stress in the NICU as well as maternal anxiety and depressive symptoms after hospitalization In contrast a cluster randomized trial of a parenting intervention delivered to mothers of very premature infants from soon after birth showed no benefits for parenting stress1 The authors hypothesized that the intervention had not been of sufficient intensity particularly in the weeks surrounding discharge Neonatal care presents a significant barrier to parent-ing in the early weeks following a very preterm birth and so inter-ventions which focus on the developmental needs of infants and the parentndashchild relationship should particularly aim to support parents as they take on the parenting role There was also concern that the intervention had failed to reach those most at risk
Since large-scale projects can be costly to implement and may often fail to reach the families in most need it may be wiser to focus on intervention programmes which are more practical and easier to implement within a neonatal care setting Research has shown that even interventions which are based on one-off meet-ings with parents of sick neonates can be effective Jotzo and Poets examined the effect of an intervention programme aimed at reducing the severity of traumatic responses as a result of giv-ing birth prematurely15 Their programme consisted of a one-off intervention meeting along with additional psychological help throughout the hospitalization of the infant The meeting cov-ered a variety of issues including a reconstruction of the events shortly before and after the infantrsquos birth relaxation techniques discussion of coping strategies available resources and social support and support during emotional outbursts The measures used included the Impact of Event Scale (IES) and the Peritrau-matic Dissociative Experience Questionnaire At discharge the mothers who received the intervention were found to have a significantly lower traumatic impact as a result of premature birth Furthermore fewer mothers in the intervention group showed symptoms of clinically significant psychological trauma at discharge compared to mothers in the control group (36 vs 76)15 The lsquoParents Circle Programrsquo is another intervention with a similar structure16 This consisted of a 90 min session for parents with the aim of enhancing the developing relationship between parents and infants and to offer parents support A total of 104 parents (59 mothers and 45 fathers) and 44 members of hospital staff were asked to evaluate the programme and their results were analysed using content analysis Families reported gaining perspective on their situation feeling supported becom-ing aware of cues and optimizing interactions and becoming aware of available resources Parents and staff alike felt that participating in the intervention helped parents overcome the difficulties associated with the early time of their infantrsquos hos-pitalization Additional studies have also found positive results with fairly minimal interventions including discussion groups
7 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
in the NICU music during kangaroo care and pairing mothers of sick neonates with trained mothers who had been through similar experiences
Parent support programmes
Parent support programmes (PSPs) which are based in NICUs can provide parents with the opportunity to talk to parents who have been in similar situations and also to discuss their emo-tions with professionals who can help them cope with their situa-tion111718 The parent-to-parent support programme for mothers of preterm infants evaluated by Preyde and Ardal included edu-cational parental support group meetings and individual par-ent-to-parent support (primarily telephone support)19 Measures used included the Parental Stressor Scale NICU the State and the Trait Anxiety Inventories and the Beck Depression Inven-tory After 4 months of participation mothers in the intervention group reported lower levels of stress state anxiety and depres-sion compared to control group mothers The authors speculated however that the participants who were able to meet face to face with other parents were those who benefited the most Hurst conducted a comprehensive survey of an NICU-based PSP This PSP was provided in a variety of formats including a weekly parent support group hospital visitation and 24-h telephone sup-port20 Of the 477 participants 303 families used the PSP dur-ing a 2-year evaluation period with 78 using only one form of support and 18 using two forms Of a sub-sample of 48 parents asked to complete an evaluation of the PSP 92 stated that they would recommend such a programme to other parents Furthermore the majority of parents felt that it made them feel supported and helped them deal with their emotions20 This is an indication that such programmes can be very successful in sup-porting parents throughout their infantrsquos hospitalization It also shows that it can be beneficial to give parents several options and formats when it comes to such support services It is impor-tant to consider though that both the Hurst and the Preyde and Ardal studies found that some participants did not find the sup-port programmes helpful even reporting that they had caused them increased stress and anxiety Therefore it should not be assumed that support programmes will suit every individual and will provide the required support for all parents1920 NICUs need to be flexible enough to provide parents with a range of forms of support to choose from
The increased understanding of the strains that parents of sick neonates have to deal with has also led to efforts to improve customary practices in NICUs Family-centred care focuses on infants and their needs and attempts to redefine the relationship between parents and caregivers These practices strive to provide parents with support during their infantrsquos illness by focusing on freely sharing information and on the collaboration between parents and hospital staff Family-centred care has been found to be associated with several beneficial outcomes including improved parental satisfaction increased parental comfort staff satisfaction and decreased parental stress18 Research is already examining these practices and questioning how these can be improved further Such research reflects the increasing effort focused on lsquohumanizingrsquo the environment in NICUs in order to make parents feel more comfortable about spending time with their infants
PaeDiaTrics anD cHilD HealTH 184 19
Conclusion
Surprisingly few interventions have prioritized the provision of emotional support for parents of sick neonates or accounted for the changing needs and wishes of parents over the course of their infantrsquos care Large-scale supportive education-based inter-ventions have been shown to be effective in reducing parental distress However the feasibility and sustainability of such pro-grammes should also be considered Programmes which require significant additional resources can be expensive and there are also issues of training and quality control Interventions which require significant input from parents may also place additional burdens on families making them potentially less accessible to those most at risk Arguably the aim should be to explore ways of providing acceptable and effective informational support which could be complemented by emotional support from health professionals and from other parents in the unit Increasingly studies are exploring the use of computers and multimedia as an engaging flexible and cost-effective method of targeting indi-vidual needs and providing support and information Such com-puter-based and interactive multimedia interventions have been found to be successful with a range of patient groups and could therefore be examined as a complementary method of providing informational support to families with sick neonates
REfEREnCEs
1 Glazebrook c Marlow n israel c et al randomised trial of a
parenting intervention during neonatal intensive care Arch Dis Child
Fetal Neonatal Ed 2007 92 F438ndash443
2 singer lT salvator a Guo s collin M lilien l Baley J Maternal
psychological distress and parenting stress after the birth of a very
low-birth-weight infant JAMA 1999 281 799ndash805
3 shaw rJ Deblois T ikuta l Ginzburg K Fleisher B Koopman c
acute stress disorder among parents of infants in the neonatal
intensive care nursery Psychosomatics 2006 47 206ndash212
4 Hopper a sources of stress for parents of a sick neonate a
literature review Pediatr Nurs 2000 30 29ndash32
5 Davis l edwards H Mohay H wollin J The impact of very
premature birth on the psychological health of mothers Early Hum
Dev 2003 73 61ndash70
6 Bernazzani O saucier J-F David H Borgeat F Psychosocial
predictors of depressive symptomatology level in postpartum
women J Affect Disord 1997 46 39ndash49
7 Field T infants of depressed mothers Infant Behav Dev 1995 18
1ndash13
8 Kaplan Ps Bachorowski J-a Zarlengo-strouse P child-directed
speech produced by mothers with symptoms of depression fails
to promote associative learning in 4-month-old infants Child Dev
1999 70 560ndash570
9 ward K Perceived needs of parents of critically ill infants in
a neonatal intensive care unit (nicU) Pediatr Nurs 2001 27
281ndash286
10 lai Hl chen cJ Peng Tc et al randomized controlled trial of music
during kangaroo care on maternal state anxiety and preterm infantsrsquo
responses Int J Nurs Stud 2006 43 139ndash146
8 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
11 Tallandini Ma scalembra c Kangaroo mother care and mother-
premature infant dyadic interaction Infant Ment Health J 2006 27
251ndash275
12 Ohgi s Fukuda M akiyama T Gima H effect of an early intervention
programme on low birthweight infants with cerebral injuries
J Paediatr Child Health 2004 40 689ndash695
13 Kaaresen Pi ronning Ja Ulvund se Dahl lB a randomized
controlled trial of the effectiveness of an early-intervention program
in reducing parenting stress after preterm birth Pediatrics 2006
118 e9ndash19
14 Melnyk BM Feinstein nF alpert-Gillis l et al reducing premature
infantsrsquo length of stay and improving parentsrsquo mental health
outcomes with the creating opportunities for parent empowerment
(cOPe) neonatal intensive care unit program a randomized
controlled trial Pediatrics 2006 118 e1414ndash1427
15 Jotzo M Poets cF Helping parents cope with the trauma of
premature birth an evaluation of a trauma-preventive psychological
intervention Pediatrics 2005 115 915ndash919
16 Pearson J andersen K evaluation of a program to promote positive
parenting in the neonatal intensive care unit Neonatal Netw 2001
20 43ndash48
17 roman l lindsay J Boger r et al Parent-to-parent support
initiated in the neonatal intensive care unit Res Nurs Health 1995
18 385ndash394
18 Meyer ec coll cTG lester BM Boukydis cFZ McDonough sM Oh w
Family-based intervention improves maternal psychological well-
being and feeding interaction of preterm infants Pediatrics 1994
93 241ndash246
PaeDiaTrics anD cHilD HealTH 184 19
19 Preyde M ardal F effectiveness of a parent ldquobuddyrdquo program for
mothers of very preterm infants in a neonatal intensive care unit
CMAJ 2003 168 969ndash973
20 Hurst i One size does not fit all Parentsrsquo evaluations of a support
program in a newborn intensive care nursery J Perinat Neonatal
Nurs 2006 20 252ndash261
Practice points
bull Parents of sick neonates experience significant distress and
exhibit higher levels of stress anxiety and depression than
parents of healthy infants
bull educational support emotional support and increased
motherndashinfant contact have been shown to promote maternal
well-being
bull emotional support for fathers has been largely neglected in
the research literature
bull Parents benefit from a choice of supportive facilities which
could include face-to-face sessions with health professionals
telephone support hospital visitation parent-to-parent
support and unit-based group support meetings
bull Parentsrsquo support needs can change during their infantrsquos
hospitalization and not all parents want or benefit from the
provision of additional information and emotional support in
the neonatal unit
9 copy 2008 elsevier ltd all rights reserved
Personal Practice
When should enteral feeds be started in preterm infantsnicholas D embleton
AbstractPaediatricians are regularly faced with the question of when best to start
enteral feeds in preterm infants this is important as longer term out-
come may be compromised by sub-optimal nutrition in early life clinical
factors that may affect the decision to start and the risk and benefits
are discussed
Keywords breast milk feeding nutrition parenteral nutrition
Key points in the history
Alice is lsquonutritionally vulnerablersquo and whilst this may not be immediately apparent it will affect her long term outcome Her energy stores are extremely limited and consist primarily of pro-tein She has less than 5 fat and little energy associated with stored glycogen She is losing about 1 gkgd protein equivalent so she needs at least that and a minimum of 50ndash60 kcalkg of energy just to maintain the status quo let alone grow
Her weight is on the 25th centile Review of any antenatal his-tory may reveal whether fetal growth was normal Fetal growth retardation can occur with a weight greater than 10th centile The presence of antenatal absent or reversed end diastolic flow in the umbilical artery indicates poor gut blood flow This increases the risk of necrotizing enterocolitis (NEC) and might suggest a more cautious approach to starting feeds1
She has no important cardiovascular problems but if she were hypotensive gut blood flow may be low There is no umbilical
Nicholas D Embleton BSC (Hons) MBBS (Hons) MD FRCPCH is Consultant in
Neonatal Medicine at Newcastle Neonatal Service Royal Victoria
Infirmary Newcastle upon Tyne NE1 4LP UK
Should you start feeds at a day of age
alice was born following spontaneous labour at 30 weeksrsquo
gestation she weighed 1300 g and is now 18 h old she was
briefly ventilated and then extubated to continuous positive
airway pressure 12 h ago in 35 oxygen she has had caffeine
citrate but still has intermittent episodes of self-correcting
apnoea she was commenced on iv 10 dextrose but this was
replaced by a parenteral amino acid solution (referred to as
lsquotPnrsquo) along with intralipid at 0900 this morning serum glucose
is 11 mmoll and blood pressure is 42 systolic
PaeDiatrics anD cHilD HealtH 184 20
arterial catheter in situ but there is no good evidence that this should delay the decision to start feeds Her glucose is high but this is quite common in a baby like this Could this be a sign of sepsis Caffeine does not affect the incidence of NEC2 The great-est risk factor for NEC in this case is prematurity
What else might be found on examination
Up until 24 h ago she was swallowing large amounts of amniotic fluid What will have changed since then
General examination should confirm peripheral perfusion lsquogestaltrsquo view (does she look lsquowellrsquo) and cardiovascular status lsquoBowel soundsrsquo are not usually helpful
The most important variable likely to affect gut perfusion is the arterial duct Precordial lsquoheaversquo and a loud murmur are sug-gestive but it is possible to have a significant ductal shunt in a baby with a normal examination Cardiac ultrasound will con-firm this diagnosis It might be better to treat a large shunt first with indometacin and to delay starting feeds for a further 24 h
It is not possible to assess gut perfusion clinically but normal perfusion elsewhere (adequate urine output usually indicates adequate renal perfusion) would be reassuring Most preterm babies have a few abdominal lsquoloopsrsquo visible but a distended abdomen with many palpable loops suggests ileus This might be secondary to sepsis or poor gut blood flow Preterm babies do not pass much meconium in the first 24ndash48 h
Balance of risks between starting and withholding feeds
Alice requires 35ndash4 gkgd of protein and 120 kcalkgd to grow3 This will initially be provided parenterally Delaying feeds increases the risk of gut villous atrophy and prolongs the need for lsquototal parenteral nutrition (TPN)rsquo TPN requires intravenous access and so increases the risk of sepsis and when prolonged use is required combined with the lack of enteral feeding may result in hepatic impairment
Delaying feeds may allow a gut that has been chronically under-perfused to re-establish more normal perfusion although normal gut endocrine function digestive enzyme upregulation and motility require a source of intraluminal nutrients1 A recent study suggested benefit from delaying the introduction of feeds4 but methodologi-cal problems exist5 Although a Cochrane meta-analysis suggested no benefit only two studies were included6 A large UK-based trial is examining the effect of early or late feeding in preterm infants who were born growth retarded following identification of antena-tal absent or reversed end diastolic flow in the umbilical artery7
When starting feeds what volume should be used
There are no good data to guide this decision We start with 24 mlkg (1 mlkgh) and then increase by this amount each day Most babies achieve full enteral feeds (ge150 mlkgd) by a week of age Feeding guidelines improve the outcome8 Measure-ment or assessment of gastric aspirates is not consistently useful in predicting subsequent feeding intolerance or development of NEC Aspirate volumes equivalent to or sometimes greater than the amount given in the preceding 1ndash2 h are usually normal Most aspirates have a greenish colour Thick bloody or intensely bile-stained aspirates require detailed assessment
0 copy 2008 elsevier ltd all rights reserved
Personal Practice
What else affects decisions and outcome
Feeding success is affected by sepsis and NEC Scrupulous atten-tion should be paid to hand washing and intravenous access and blood sampling should be minimized There is no good evidence to support the routine use of pro-kinetic agents or H2 blockers
The most important clinical intervention affecting the occur-rence of NEC is the use of breast milk9 All efforts should be directed at persuading parents of the benefits and supporting the process Some clinicians delay starting feeds for a further 24 h whilst expressed breast milk becomes available Donor breast milk might be equally efficacious10
RefeRenceS
1 Dorling J Kempley s leaf a Feeding growth restricted preterm
infants with abnormal antenatal Doppler results Arch Dis Child Fetal
Neonatal Ed 2005 90 F359ndash363
2 schmidt B roberts rs Davis P et al caffeine therapy for apnea of
prematurity N Engl J Med 2006 354 2112ndash2121
PaeDiatrics anD cHilD HealtH 184 20
3 embleton nD Pang n cooke rJ Postnatal malnutrition and growth
retardation an inevitable consequence of current recommendations
in preterm infants Pediatrics 2001 107 270ndash273
4 Berseth cl Bisquera Ja Paje VU Prolonging small feeding volumes
early in life decreases the incidence of necrotizing enterocolitis in
very low birth weight infants Pediatrics 2003 111 529ndash534
5 Menon G Boyle eM embleton nD et al introduction of enteral
feeds in preterm infants Pediatrics 2004 114 327ndash328
6 Kennedy Ka tyson Je chamnanvanikij s early versus delayed
initiation of progressive enteral feedings for parenterally fed low
birth weight or preterm infants Cochrane Database Syst Rev 2000
cD001970
7 wwwnpeuoxacukadept
8 Patole sK de Klerk n impact of standardised feeding regimens on
incidence of neonatal necrotising enterocolitis a systematic review
and meta-analysis of observational studies Arch Dis Child Fetal
Neonatal Ed 2005 90 F147ndash151
9 lucas a cole tJ Breast milk and neonatal necrotising enterocolitis
Lancet 1990 336 1519ndash1523
10 Boyd ca Quigley Ma Brocklehurst P Donor breast milk versus
infant formula for preterm infants systematic review and meta-
analysis Arch Dis Child Fetal Neonatal Ed 2007 92 F169ndash175
1 copy 2008 elsevier ltd all rights reserved
self-assessment
Case 1A term male infant born to consanguineous parents is assessed at 24 h of age due to poor feeding profuse yellow watery diar-rhoea and irritability He weighed 32 kg at birth and delivery was uneventful There was no polyhydramnios He has been breastfed since birth On examination he is pale with a non-tender but distended abdomen and reduced bowel sounds His weight is 275 kg and he looks dehydrated Examination is otherwise normal
Initial investigations (normal values in parentheses) showed
sodium 149 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 65 mmollitre (25ndash75)
creatinine 147 μmollitre (40ndash110)
chloride 119 mmollitre (95ndash105)
haemoglobin 172 gdl (140ndash200)
White blood cell count 80 times 109litre (100ndash260)
Platelet count 302 times 109litre (150ndash400)
arterial blood gas
ph 720 (730ndash745)
PcO2 23 kPa (46ndash60)
Bicarbonate 68 mmollitre (220ndash260)
Base excess minus186 mmollitre (minus20 to +20)
lactate 59 mmollitre (06ndash24)
An abdominal X-ray shows distended bowel loops with no intramural thickening or pneumoperitoneum (Figure 1)
He was given nil by mouth and received intravenous fluids and antibiotics His dehydration improved but the metabolic acidosis and diarrhoea persisted despite receiving no enteral feeds and the commencement of total parenteral nutrition Blood and stool cultures were negative
1 Which of the following best describes these results Choose ONE answer ONLY from the followingA Hypernatraemia hyperchloraemic metabolic acidosis
with increased anion gapB Hypernatraemia hyperchloraemic metabolic acidosis
with normal anion gap
Manish Sadarangani BM BCh MA MRCPCH is Clinical Research Fellow
at the Department of Paediatrics University of Oxford Centre for
Clinical Vaccinology and Tropical Medicine Churchill Hospital
Oxford OX3 7LJ UK
Shabna Rajapaksa MB BChir MA MRCPCH is Specialist Registrar in
Paediatrics at the Paediatric Intensive Care Unit John Radcliffe
Hospital Oxford OX3 9DU UK
Nicholas Mann MD FRCP FRCPCH DCH is Consultant Paediatrician at the
Department of Paediatrics Royal Berkshire Hospital Reading RG1
5AN UK
self-assessment
C Hypernatraemic dehydration and compensated metabolic acidosis
D Acute renal failureE Renal tubular acidosis
2 What is the likely diagnosis Choose ONE answer ONLY from the followingA Hirschsprung disease ndash long segmentB Cystic fibrosis with meconium ileusC Microvillus inclusion diseaseD Cowrsquos milk protein intoleranceE Lactose intolerance
3 What is the investigation of choice Choose ONE answer ONLY from the followingA Rectal biopsy with staining for acetylcholine receptorsB Immunoreactive trypsinC Gastrointestinal endoscopy and biopsyD Stool microscopy and cultureE Stool reducing substances
Case 2A 4-year-old boy presents with a 3 d history of jaundice and a florid rash He has had orange urine and there is no change in his stool colour His family originate from Kosovo and have lived in the UK for the last 8 years He has never left the UK There is no history of blood transfusion or sex-ual abuse The grandmother was recently diagnosed with hepatitis B
On examination he is well apyrexial and mildly jaundiced with cervical and axillary lymphadenopathy He has an exten-sive papular rash over the face extremities and trunk (Figure 2) There is 3 cm hepatomegaly with no splenomegaly or ascites Examination is otherwise normal
Figure 1 abdominal X-ray of baby
Paediatrics and child health 184 202 copy 2008 elsevier ltd all rights reserved
self-assessment
Initial investigations are as follows
haemoglobin 110 gdl (113ndash135)
White blood cell count 108 times 109litre (50ndash150)
Platelet count 278 times 109litre (150ndash400)
inr 10 (08ndash12)
aPt ratio 10 (08ndash13)
sodium 140 mmollitre (135ndash145)
Potassium 42 mmollitre (35ndash50)
Urea 56 mmollitre (25ndash75)
creatinine 65 μmollitre (45ndash120)
total bilirubin 66 μmollitre (0ndash15)
conjugated bilirubin 23 μmollitre (0ndash10)
alanine aminotransferase (alt) 2033 iUlitre (0ndash35)
alkaline phosphatase 987 iUlitre (71ndash234)
Gamma-glutamyl transferase (GGt) 870 iUlitre (0ndash51)
1 What is the name of this rash Choose ONE answer ONLY from the followingA Erythema multiformeB Erythema migransC GianottiminusCrosti syndromeD EczemaE Dermatitis herpetiformis
2 What is the most likely diagnosis Choose ONE Answer ONLY from the followingA Autoimmune hepatitisB Hepatitis BC Hepatitis DD Wilson diseaseE Alpha-1 antitrypsin deficiency
3 What is the best means of management Choose ONE answer ONLY from the followingA Isolation until the jaundice disappearsB ImmunosuppressionC Copper chelating agents and genetic counsellingD Patient and family education with consideration of
antiviral agentsE Liver transplantation
Case 3A 10-month-old boy presents with 3 weeks of vomiting and constipation ndash he is passing hard stools every 2ndash3 days He has fallen from the 9th to below the 04th centile in the last 6 weeks He passed meconium within the first 24 h of life On examina-tion he looks pale and there are some dysmorphic features ndash a short nose long philtrum and wide mouth He has normal heart sounds with a grade 3 ejection systolic murmur loudest at the upper right sternal edge Examination is otherwise normal
Initial investigations are as follows
haemoglobin 91 gdl (113ndash141)
total white blood cell count 124 times 109litre (60ndash170)
Platelet count 407 times 109litre (150ndash400)
sodium 144 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 78 mmollitre (25ndash75)
creatinine 78 μmollitre (45ndash120)
albumin 52 glitre (35ndash50)
corrected calcium 384 mmollitre (238ndash263)
Phosphate 167 mmollitre (099ndash157)
1 What is the most likely diagnosis Choose ONE answer ONLY from the followingA HyperparathyroidismB Acute leukaemiaC Williams syndromeD Hypervitaminosis DE Familial hypocalciuric hypercalcaemia
2 Which investigation would be most useful in establishing the diagnosis Choose ONE answer ONLY from the followingA Intact parathyroid hormone assayB Blood filmC Fluorescent in-situ hybridization for 7q1123 deletionD 25-hydroxyvitamin D assayE Urine calciumcreatinine ratio
3 Which of the following treatments would not be suitable for this patient Choose ONE answer ONLY from the followingA Low calcium dietB Normal saline infusionC FurosemideD CorticosteroidsE Bisphosphonates
Case 4A 10-week-old girl presents with a 2-day history of poor feed-ing Her mother has been concerned about weakness since birth She only has a flicker of movement in the arms none in the legs and has a weak cry She has been passing urine and opening her bowels normally She was born at full term by normal delivery and did not require any resuscitation at birth Normal fetal movements were felt antenatally and there was no polyhydramnios She is the first child of non- consanguineous parents and there is no significant family his-tory On examination she is alert and fixing and following appropriately She has a weak cry and a weak suck There is reduced central and peripheral tone with marked head lag
Figure 2 rash found on examination
Paediatrics and child health 184 203 copy 2008 elsevier ltd all rights reserved
self-assessment
Muscle power is grade 3 out of 5 in the arms and legs There is no muscle or tongue fasciculation and she has absent reflexes throughout The remainder of the examination is normal
Electromyogram shows irregular polyphasic motor unit potentials with marked instability consistent with a dener-vating and re-innervating process (Figure 3)
1 Which of the following additional investigations may be helpful Choose ONE answer ONLY from the followingA Nerve conduction studiesB Creatine kinase assayC Muscle biopsyD SMN1 gene analysisE All of the above
2 What is the most likely cause of this childrsquos symptoms Choose ONE answer ONLY from the followingA Congenital myotonic dystrophyB Duchenne muscular dystrophyC PraderminusWilli syndromeD Spinal muscular atrophyE Mitochondrial myopathy
3 What is the mode of inheritance of this disease Choose ONE answer ONLY from the followingA X-linked recessiveB Autosomal recessiveC Autosomal dominantD MitochondrialE Sporadic
Case 5A 13-year-old girl presents with a 3-week history of fever up to 40degC night sweats and headache She has a reduced appetite with some weight loss She has no other specific symptoms She was on holiday in China 7 months ago On examination she looks well and has a temperature of 387degC There is no lymphadenopathy and no rashes Examination is entirely normal
Results of investigations are as follows
haemoglobin 126 gdl (120ndash160)
total white blood cell count 132 times 109litre (43ndash108)
neutrophil count 115 times 109litre (25ndash75)
Platelet count 244 times 109litre (150ndash400)
Blood film neutrophilia with left shift
erythrocyte sedimentation rate 63 mmh (1ndash20)
c-reactive protein 219 mglitre (0ndash5)
Blood culture Streptococcus intermedius
from anaerobic bottle only
csf culture negative
Magnetic resonance imaging (MRI) of the brain shows acute frontal sinusitis with a large intracranial frontal extra-dural empyema (Figure 4)
1 Which of the following would be appropriate management Choose ONE answer ONLY from the followingA A 12-week course of intravenous antibioticsB Drainage of the frontal sinus followed by 2 weeks of
intravenous antibioticsC Drainage of the empyema followed by 2 weeks of
intravenous antibioticsD Drainage of the empyema and the frontal sinus
followed by 2 weeks of oral antibiotics
1151
1152
1153
1154
1155
1156
1157
1158
1159
1200
50ms 1mV
Figure 3 electromyogram recording from the patient Figure 4 Parasagittal section from mri scan of patient
Paediatrics and child health 184 204 copy 2008 elsevier ltd all rights reserved
self-assessment
E Drainage of the empyema and the frontal sinus followed by 8 weeks of intravenous antibiotics
2 Streptococcus intermedius is a potential pathogen in which of the following infections Choose ONE answer ONLY from the followingA Liver abscessB Urinary tract infectionC MeningitisD Thoracic empyemaE Pneumonia
3 Which of the following statements regarding lsquopyrexia of unknown originrsquo in children is false Choose ONE answer ONLY from the followingA Malignancy is the underlying pathology in 5ndash15 of
casesB An aetiology will be found in over 90 of casesC The most common cause is infectionD A rheumatological cause is found in 10ndash20 of casesE Familial Mediterranean fever can occur in children of
non-Mediterranean ethnicity
Answers
Case 11 AThe anion gap is a useful tool to differentiate the causes of a metabolic acidosis It is calculated by the equation
Anion gap = [Na K ] [Cl HCO ]3+ + minus minus+ minus +
It represents the effect of unmeasured anions on the plasma pH and is normally 10ndash18 mmollitre
2 CMicrovillus inclusion disease is a severe autosomal recessive enteropathy that is typically apparent within hours or days after birth It is the second most common cause of protracted diarrhoea in the newborn after infectious causes It is characterized by severe yellow watery diarrhoea and malabsorption due to hypoplasia andor atrophy of the villi of the small intestine secondary to an inherited defect in the brush border membrane This results in severe dehydration malnutrition and metabolic acidosis due to bicarbonate loss from the gut
3 CDiagnosis of microvillus inclusion disease is made on small bowel biopsy Electron microscopy findings are of intracellular brush border inclusions and densely packed apical cytoplasmic vesicular bodies indicating microvillous atrophy There is no cure Treatment is supportive with total parenteral nutrition and consideration of small bowel transplantation
Further reAding
Goulet O ruemmele f causes and management of intestinal failure
in children Gastroenterology 2006 130(suppl 1) s16ndash28
rhoads Jm Vogler rc lacey sr et al microvillus inclusion disease
In vitro jejunal electrolyte transport Gastroenterology 1991
100 811ndash817
Case 21 CGianottindashCrosti syndrome is a distinct self-limiting rash commonly associated with viral infections in children between 2 and 6 years of age It presents as multiple pink to redminusbrown papules or papulovesicles which may be pruritic and can become confluent Gianotti and Crosti initially described the exanthema as associated with hepatitis B virus and they termed it papular acrodermatitis of childhood It can occur in several viral diseases eg hepatitis A B and C coxsackie viruses and cytomegalovirus
2 BHepatitis is a syndrome characterized by inflammation or injury of liver cells which may develop into cell necrosis and subsequently fibrosis andor cirrhosis Biochemically there are raised liver enzymes The degree of transaminase elevation does not correlate with the severity of the disease process Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of viral hepatitis
3 DHepatitis B infection is transmitted via blood sexually or vertically Infection may be acute or chronic Diagnostic markers are the presence of surface antigen (HBsAg) and HBV DNA The presence of e antigen (HBeAg) indicates high infectivity Infected newborns have a 95 risk of becoming carriers this risk decreases with infection acquired later in childhood Approximately 15ndash25 of HBV carriers will die from cirrhosis or hepatocellular carcinoma Extrahepatic findings are more common in older children and include membranous glomerulonephritis and GianottiminusCrosti syndrome Fulminant hepatic failure occurs in severe cases resulting in persistent jaundice encephalopathy and coagulopathy Management includes counselling family members monitoring for ongoing liver disease and consideration of antiviral therapy
Further reAding
Brandt O abeck d Gianotti r Burgdorf W Gianotti crosti
syndrome J Am Acad Dermatol 2006 54 136ndash145
slowik mK Jhaveri r hepatitis B and c viruses in infants and
young children Semin Pediatr Infect Dis 2005 16 296ndash305
Case 31 CHypercalcaemia is uncommon in infancy The most common symptoms in this age group are irritability vomiting and constipation It may be a manifestation of Williams syndrome vitamin D or calcium excess as well as disorders associated with reduced bone formation such as hypophosphatasia or increased bone resorption such as malignancy Occasionally
Paediatrics and child health 184 205 copy 2008 elsevier ltd all rights reserved
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-
OccasiOnal review
in the NICU music during kangaroo care and pairing mothers of sick neonates with trained mothers who had been through similar experiences
Parent support programmes
Parent support programmes (PSPs) which are based in NICUs can provide parents with the opportunity to talk to parents who have been in similar situations and also to discuss their emo-tions with professionals who can help them cope with their situa-tion111718 The parent-to-parent support programme for mothers of preterm infants evaluated by Preyde and Ardal included edu-cational parental support group meetings and individual par-ent-to-parent support (primarily telephone support)19 Measures used included the Parental Stressor Scale NICU the State and the Trait Anxiety Inventories and the Beck Depression Inven-tory After 4 months of participation mothers in the intervention group reported lower levels of stress state anxiety and depres-sion compared to control group mothers The authors speculated however that the participants who were able to meet face to face with other parents were those who benefited the most Hurst conducted a comprehensive survey of an NICU-based PSP This PSP was provided in a variety of formats including a weekly parent support group hospital visitation and 24-h telephone sup-port20 Of the 477 participants 303 families used the PSP dur-ing a 2-year evaluation period with 78 using only one form of support and 18 using two forms Of a sub-sample of 48 parents asked to complete an evaluation of the PSP 92 stated that they would recommend such a programme to other parents Furthermore the majority of parents felt that it made them feel supported and helped them deal with their emotions20 This is an indication that such programmes can be very successful in sup-porting parents throughout their infantrsquos hospitalization It also shows that it can be beneficial to give parents several options and formats when it comes to such support services It is impor-tant to consider though that both the Hurst and the Preyde and Ardal studies found that some participants did not find the sup-port programmes helpful even reporting that they had caused them increased stress and anxiety Therefore it should not be assumed that support programmes will suit every individual and will provide the required support for all parents1920 NICUs need to be flexible enough to provide parents with a range of forms of support to choose from
The increased understanding of the strains that parents of sick neonates have to deal with has also led to efforts to improve customary practices in NICUs Family-centred care focuses on infants and their needs and attempts to redefine the relationship between parents and caregivers These practices strive to provide parents with support during their infantrsquos illness by focusing on freely sharing information and on the collaboration between parents and hospital staff Family-centred care has been found to be associated with several beneficial outcomes including improved parental satisfaction increased parental comfort staff satisfaction and decreased parental stress18 Research is already examining these practices and questioning how these can be improved further Such research reflects the increasing effort focused on lsquohumanizingrsquo the environment in NICUs in order to make parents feel more comfortable about spending time with their infants
PaeDiaTrics anD cHilD HealTH 184 19
Conclusion
Surprisingly few interventions have prioritized the provision of emotional support for parents of sick neonates or accounted for the changing needs and wishes of parents over the course of their infantrsquos care Large-scale supportive education-based inter-ventions have been shown to be effective in reducing parental distress However the feasibility and sustainability of such pro-grammes should also be considered Programmes which require significant additional resources can be expensive and there are also issues of training and quality control Interventions which require significant input from parents may also place additional burdens on families making them potentially less accessible to those most at risk Arguably the aim should be to explore ways of providing acceptable and effective informational support which could be complemented by emotional support from health professionals and from other parents in the unit Increasingly studies are exploring the use of computers and multimedia as an engaging flexible and cost-effective method of targeting indi-vidual needs and providing support and information Such com-puter-based and interactive multimedia interventions have been found to be successful with a range of patient groups and could therefore be examined as a complementary method of providing informational support to families with sick neonates
REfEREnCEs
1 Glazebrook c Marlow n israel c et al randomised trial of a
parenting intervention during neonatal intensive care Arch Dis Child
Fetal Neonatal Ed 2007 92 F438ndash443
2 singer lT salvator a Guo s collin M lilien l Baley J Maternal
psychological distress and parenting stress after the birth of a very
low-birth-weight infant JAMA 1999 281 799ndash805
3 shaw rJ Deblois T ikuta l Ginzburg K Fleisher B Koopman c
acute stress disorder among parents of infants in the neonatal
intensive care nursery Psychosomatics 2006 47 206ndash212
4 Hopper a sources of stress for parents of a sick neonate a
literature review Pediatr Nurs 2000 30 29ndash32
5 Davis l edwards H Mohay H wollin J The impact of very
premature birth on the psychological health of mothers Early Hum
Dev 2003 73 61ndash70
6 Bernazzani O saucier J-F David H Borgeat F Psychosocial
predictors of depressive symptomatology level in postpartum
women J Affect Disord 1997 46 39ndash49
7 Field T infants of depressed mothers Infant Behav Dev 1995 18
1ndash13
8 Kaplan Ps Bachorowski J-a Zarlengo-strouse P child-directed
speech produced by mothers with symptoms of depression fails
to promote associative learning in 4-month-old infants Child Dev
1999 70 560ndash570
9 ward K Perceived needs of parents of critically ill infants in
a neonatal intensive care unit (nicU) Pediatr Nurs 2001 27
281ndash286
10 lai Hl chen cJ Peng Tc et al randomized controlled trial of music
during kangaroo care on maternal state anxiety and preterm infantsrsquo
responses Int J Nurs Stud 2006 43 139ndash146
8 copy 2008 elsevier ltd all rights reserved
OccasiOnal review
11 Tallandini Ma scalembra c Kangaroo mother care and mother-
premature infant dyadic interaction Infant Ment Health J 2006 27
251ndash275
12 Ohgi s Fukuda M akiyama T Gima H effect of an early intervention
programme on low birthweight infants with cerebral injuries
J Paediatr Child Health 2004 40 689ndash695
13 Kaaresen Pi ronning Ja Ulvund se Dahl lB a randomized
controlled trial of the effectiveness of an early-intervention program
in reducing parenting stress after preterm birth Pediatrics 2006
118 e9ndash19
14 Melnyk BM Feinstein nF alpert-Gillis l et al reducing premature
infantsrsquo length of stay and improving parentsrsquo mental health
outcomes with the creating opportunities for parent empowerment
(cOPe) neonatal intensive care unit program a randomized
controlled trial Pediatrics 2006 118 e1414ndash1427
15 Jotzo M Poets cF Helping parents cope with the trauma of
premature birth an evaluation of a trauma-preventive psychological
intervention Pediatrics 2005 115 915ndash919
16 Pearson J andersen K evaluation of a program to promote positive
parenting in the neonatal intensive care unit Neonatal Netw 2001
20 43ndash48
17 roman l lindsay J Boger r et al Parent-to-parent support
initiated in the neonatal intensive care unit Res Nurs Health 1995
18 385ndash394
18 Meyer ec coll cTG lester BM Boukydis cFZ McDonough sM Oh w
Family-based intervention improves maternal psychological well-
being and feeding interaction of preterm infants Pediatrics 1994
93 241ndash246
PaeDiaTrics anD cHilD HealTH 184 19
19 Preyde M ardal F effectiveness of a parent ldquobuddyrdquo program for
mothers of very preterm infants in a neonatal intensive care unit
CMAJ 2003 168 969ndash973
20 Hurst i One size does not fit all Parentsrsquo evaluations of a support
program in a newborn intensive care nursery J Perinat Neonatal
Nurs 2006 20 252ndash261
Practice points
bull Parents of sick neonates experience significant distress and
exhibit higher levels of stress anxiety and depression than
parents of healthy infants
bull educational support emotional support and increased
motherndashinfant contact have been shown to promote maternal
well-being
bull emotional support for fathers has been largely neglected in
the research literature
bull Parents benefit from a choice of supportive facilities which
could include face-to-face sessions with health professionals
telephone support hospital visitation parent-to-parent
support and unit-based group support meetings
bull Parentsrsquo support needs can change during their infantrsquos
hospitalization and not all parents want or benefit from the
provision of additional information and emotional support in
the neonatal unit
9 copy 2008 elsevier ltd all rights reserved
Personal Practice
When should enteral feeds be started in preterm infantsnicholas D embleton
AbstractPaediatricians are regularly faced with the question of when best to start
enteral feeds in preterm infants this is important as longer term out-
come may be compromised by sub-optimal nutrition in early life clinical
factors that may affect the decision to start and the risk and benefits
are discussed
Keywords breast milk feeding nutrition parenteral nutrition
Key points in the history
Alice is lsquonutritionally vulnerablersquo and whilst this may not be immediately apparent it will affect her long term outcome Her energy stores are extremely limited and consist primarily of pro-tein She has less than 5 fat and little energy associated with stored glycogen She is losing about 1 gkgd protein equivalent so she needs at least that and a minimum of 50ndash60 kcalkg of energy just to maintain the status quo let alone grow
Her weight is on the 25th centile Review of any antenatal his-tory may reveal whether fetal growth was normal Fetal growth retardation can occur with a weight greater than 10th centile The presence of antenatal absent or reversed end diastolic flow in the umbilical artery indicates poor gut blood flow This increases the risk of necrotizing enterocolitis (NEC) and might suggest a more cautious approach to starting feeds1
She has no important cardiovascular problems but if she were hypotensive gut blood flow may be low There is no umbilical
Nicholas D Embleton BSC (Hons) MBBS (Hons) MD FRCPCH is Consultant in
Neonatal Medicine at Newcastle Neonatal Service Royal Victoria
Infirmary Newcastle upon Tyne NE1 4LP UK
Should you start feeds at a day of age
alice was born following spontaneous labour at 30 weeksrsquo
gestation she weighed 1300 g and is now 18 h old she was
briefly ventilated and then extubated to continuous positive
airway pressure 12 h ago in 35 oxygen she has had caffeine
citrate but still has intermittent episodes of self-correcting
apnoea she was commenced on iv 10 dextrose but this was
replaced by a parenteral amino acid solution (referred to as
lsquotPnrsquo) along with intralipid at 0900 this morning serum glucose
is 11 mmoll and blood pressure is 42 systolic
PaeDiatrics anD cHilD HealtH 184 20
arterial catheter in situ but there is no good evidence that this should delay the decision to start feeds Her glucose is high but this is quite common in a baby like this Could this be a sign of sepsis Caffeine does not affect the incidence of NEC2 The great-est risk factor for NEC in this case is prematurity
What else might be found on examination
Up until 24 h ago she was swallowing large amounts of amniotic fluid What will have changed since then
General examination should confirm peripheral perfusion lsquogestaltrsquo view (does she look lsquowellrsquo) and cardiovascular status lsquoBowel soundsrsquo are not usually helpful
The most important variable likely to affect gut perfusion is the arterial duct Precordial lsquoheaversquo and a loud murmur are sug-gestive but it is possible to have a significant ductal shunt in a baby with a normal examination Cardiac ultrasound will con-firm this diagnosis It might be better to treat a large shunt first with indometacin and to delay starting feeds for a further 24 h
It is not possible to assess gut perfusion clinically but normal perfusion elsewhere (adequate urine output usually indicates adequate renal perfusion) would be reassuring Most preterm babies have a few abdominal lsquoloopsrsquo visible but a distended abdomen with many palpable loops suggests ileus This might be secondary to sepsis or poor gut blood flow Preterm babies do not pass much meconium in the first 24ndash48 h
Balance of risks between starting and withholding feeds
Alice requires 35ndash4 gkgd of protein and 120 kcalkgd to grow3 This will initially be provided parenterally Delaying feeds increases the risk of gut villous atrophy and prolongs the need for lsquototal parenteral nutrition (TPN)rsquo TPN requires intravenous access and so increases the risk of sepsis and when prolonged use is required combined with the lack of enteral feeding may result in hepatic impairment
Delaying feeds may allow a gut that has been chronically under-perfused to re-establish more normal perfusion although normal gut endocrine function digestive enzyme upregulation and motility require a source of intraluminal nutrients1 A recent study suggested benefit from delaying the introduction of feeds4 but methodologi-cal problems exist5 Although a Cochrane meta-analysis suggested no benefit only two studies were included6 A large UK-based trial is examining the effect of early or late feeding in preterm infants who were born growth retarded following identification of antena-tal absent or reversed end diastolic flow in the umbilical artery7
When starting feeds what volume should be used
There are no good data to guide this decision We start with 24 mlkg (1 mlkgh) and then increase by this amount each day Most babies achieve full enteral feeds (ge150 mlkgd) by a week of age Feeding guidelines improve the outcome8 Measure-ment or assessment of gastric aspirates is not consistently useful in predicting subsequent feeding intolerance or development of NEC Aspirate volumes equivalent to or sometimes greater than the amount given in the preceding 1ndash2 h are usually normal Most aspirates have a greenish colour Thick bloody or intensely bile-stained aspirates require detailed assessment
0 copy 2008 elsevier ltd all rights reserved
Personal Practice
What else affects decisions and outcome
Feeding success is affected by sepsis and NEC Scrupulous atten-tion should be paid to hand washing and intravenous access and blood sampling should be minimized There is no good evidence to support the routine use of pro-kinetic agents or H2 blockers
The most important clinical intervention affecting the occur-rence of NEC is the use of breast milk9 All efforts should be directed at persuading parents of the benefits and supporting the process Some clinicians delay starting feeds for a further 24 h whilst expressed breast milk becomes available Donor breast milk might be equally efficacious10
RefeRenceS
1 Dorling J Kempley s leaf a Feeding growth restricted preterm
infants with abnormal antenatal Doppler results Arch Dis Child Fetal
Neonatal Ed 2005 90 F359ndash363
2 schmidt B roberts rs Davis P et al caffeine therapy for apnea of
prematurity N Engl J Med 2006 354 2112ndash2121
PaeDiatrics anD cHilD HealtH 184 20
3 embleton nD Pang n cooke rJ Postnatal malnutrition and growth
retardation an inevitable consequence of current recommendations
in preterm infants Pediatrics 2001 107 270ndash273
4 Berseth cl Bisquera Ja Paje VU Prolonging small feeding volumes
early in life decreases the incidence of necrotizing enterocolitis in
very low birth weight infants Pediatrics 2003 111 529ndash534
5 Menon G Boyle eM embleton nD et al introduction of enteral
feeds in preterm infants Pediatrics 2004 114 327ndash328
6 Kennedy Ka tyson Je chamnanvanikij s early versus delayed
initiation of progressive enteral feedings for parenterally fed low
birth weight or preterm infants Cochrane Database Syst Rev 2000
cD001970
7 wwwnpeuoxacukadept
8 Patole sK de Klerk n impact of standardised feeding regimens on
incidence of neonatal necrotising enterocolitis a systematic review
and meta-analysis of observational studies Arch Dis Child Fetal
Neonatal Ed 2005 90 F147ndash151
9 lucas a cole tJ Breast milk and neonatal necrotising enterocolitis
Lancet 1990 336 1519ndash1523
10 Boyd ca Quigley Ma Brocklehurst P Donor breast milk versus
infant formula for preterm infants systematic review and meta-
analysis Arch Dis Child Fetal Neonatal Ed 2007 92 F169ndash175
1 copy 2008 elsevier ltd all rights reserved
self-assessment
Case 1A term male infant born to consanguineous parents is assessed at 24 h of age due to poor feeding profuse yellow watery diar-rhoea and irritability He weighed 32 kg at birth and delivery was uneventful There was no polyhydramnios He has been breastfed since birth On examination he is pale with a non-tender but distended abdomen and reduced bowel sounds His weight is 275 kg and he looks dehydrated Examination is otherwise normal
Initial investigations (normal values in parentheses) showed
sodium 149 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 65 mmollitre (25ndash75)
creatinine 147 μmollitre (40ndash110)
chloride 119 mmollitre (95ndash105)
haemoglobin 172 gdl (140ndash200)
White blood cell count 80 times 109litre (100ndash260)
Platelet count 302 times 109litre (150ndash400)
arterial blood gas
ph 720 (730ndash745)
PcO2 23 kPa (46ndash60)
Bicarbonate 68 mmollitre (220ndash260)
Base excess minus186 mmollitre (minus20 to +20)
lactate 59 mmollitre (06ndash24)
An abdominal X-ray shows distended bowel loops with no intramural thickening or pneumoperitoneum (Figure 1)
He was given nil by mouth and received intravenous fluids and antibiotics His dehydration improved but the metabolic acidosis and diarrhoea persisted despite receiving no enteral feeds and the commencement of total parenteral nutrition Blood and stool cultures were negative
1 Which of the following best describes these results Choose ONE answer ONLY from the followingA Hypernatraemia hyperchloraemic metabolic acidosis
with increased anion gapB Hypernatraemia hyperchloraemic metabolic acidosis
with normal anion gap
Manish Sadarangani BM BCh MA MRCPCH is Clinical Research Fellow
at the Department of Paediatrics University of Oxford Centre for
Clinical Vaccinology and Tropical Medicine Churchill Hospital
Oxford OX3 7LJ UK
Shabna Rajapaksa MB BChir MA MRCPCH is Specialist Registrar in
Paediatrics at the Paediatric Intensive Care Unit John Radcliffe
Hospital Oxford OX3 9DU UK
Nicholas Mann MD FRCP FRCPCH DCH is Consultant Paediatrician at the
Department of Paediatrics Royal Berkshire Hospital Reading RG1
5AN UK
self-assessment
C Hypernatraemic dehydration and compensated metabolic acidosis
D Acute renal failureE Renal tubular acidosis
2 What is the likely diagnosis Choose ONE answer ONLY from the followingA Hirschsprung disease ndash long segmentB Cystic fibrosis with meconium ileusC Microvillus inclusion diseaseD Cowrsquos milk protein intoleranceE Lactose intolerance
3 What is the investigation of choice Choose ONE answer ONLY from the followingA Rectal biopsy with staining for acetylcholine receptorsB Immunoreactive trypsinC Gastrointestinal endoscopy and biopsyD Stool microscopy and cultureE Stool reducing substances
Case 2A 4-year-old boy presents with a 3 d history of jaundice and a florid rash He has had orange urine and there is no change in his stool colour His family originate from Kosovo and have lived in the UK for the last 8 years He has never left the UK There is no history of blood transfusion or sex-ual abuse The grandmother was recently diagnosed with hepatitis B
On examination he is well apyrexial and mildly jaundiced with cervical and axillary lymphadenopathy He has an exten-sive papular rash over the face extremities and trunk (Figure 2) There is 3 cm hepatomegaly with no splenomegaly or ascites Examination is otherwise normal
Figure 1 abdominal X-ray of baby
Paediatrics and child health 184 202 copy 2008 elsevier ltd all rights reserved
self-assessment
Initial investigations are as follows
haemoglobin 110 gdl (113ndash135)
White blood cell count 108 times 109litre (50ndash150)
Platelet count 278 times 109litre (150ndash400)
inr 10 (08ndash12)
aPt ratio 10 (08ndash13)
sodium 140 mmollitre (135ndash145)
Potassium 42 mmollitre (35ndash50)
Urea 56 mmollitre (25ndash75)
creatinine 65 μmollitre (45ndash120)
total bilirubin 66 μmollitre (0ndash15)
conjugated bilirubin 23 μmollitre (0ndash10)
alanine aminotransferase (alt) 2033 iUlitre (0ndash35)
alkaline phosphatase 987 iUlitre (71ndash234)
Gamma-glutamyl transferase (GGt) 870 iUlitre (0ndash51)
1 What is the name of this rash Choose ONE answer ONLY from the followingA Erythema multiformeB Erythema migransC GianottiminusCrosti syndromeD EczemaE Dermatitis herpetiformis
2 What is the most likely diagnosis Choose ONE Answer ONLY from the followingA Autoimmune hepatitisB Hepatitis BC Hepatitis DD Wilson diseaseE Alpha-1 antitrypsin deficiency
3 What is the best means of management Choose ONE answer ONLY from the followingA Isolation until the jaundice disappearsB ImmunosuppressionC Copper chelating agents and genetic counsellingD Patient and family education with consideration of
antiviral agentsE Liver transplantation
Case 3A 10-month-old boy presents with 3 weeks of vomiting and constipation ndash he is passing hard stools every 2ndash3 days He has fallen from the 9th to below the 04th centile in the last 6 weeks He passed meconium within the first 24 h of life On examina-tion he looks pale and there are some dysmorphic features ndash a short nose long philtrum and wide mouth He has normal heart sounds with a grade 3 ejection systolic murmur loudest at the upper right sternal edge Examination is otherwise normal
Initial investigations are as follows
haemoglobin 91 gdl (113ndash141)
total white blood cell count 124 times 109litre (60ndash170)
Platelet count 407 times 109litre (150ndash400)
sodium 144 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 78 mmollitre (25ndash75)
creatinine 78 μmollitre (45ndash120)
albumin 52 glitre (35ndash50)
corrected calcium 384 mmollitre (238ndash263)
Phosphate 167 mmollitre (099ndash157)
1 What is the most likely diagnosis Choose ONE answer ONLY from the followingA HyperparathyroidismB Acute leukaemiaC Williams syndromeD Hypervitaminosis DE Familial hypocalciuric hypercalcaemia
2 Which investigation would be most useful in establishing the diagnosis Choose ONE answer ONLY from the followingA Intact parathyroid hormone assayB Blood filmC Fluorescent in-situ hybridization for 7q1123 deletionD 25-hydroxyvitamin D assayE Urine calciumcreatinine ratio
3 Which of the following treatments would not be suitable for this patient Choose ONE answer ONLY from the followingA Low calcium dietB Normal saline infusionC FurosemideD CorticosteroidsE Bisphosphonates
Case 4A 10-week-old girl presents with a 2-day history of poor feed-ing Her mother has been concerned about weakness since birth She only has a flicker of movement in the arms none in the legs and has a weak cry She has been passing urine and opening her bowels normally She was born at full term by normal delivery and did not require any resuscitation at birth Normal fetal movements were felt antenatally and there was no polyhydramnios She is the first child of non- consanguineous parents and there is no significant family his-tory On examination she is alert and fixing and following appropriately She has a weak cry and a weak suck There is reduced central and peripheral tone with marked head lag
Figure 2 rash found on examination
Paediatrics and child health 184 203 copy 2008 elsevier ltd all rights reserved
self-assessment
Muscle power is grade 3 out of 5 in the arms and legs There is no muscle or tongue fasciculation and she has absent reflexes throughout The remainder of the examination is normal
Electromyogram shows irregular polyphasic motor unit potentials with marked instability consistent with a dener-vating and re-innervating process (Figure 3)
1 Which of the following additional investigations may be helpful Choose ONE answer ONLY from the followingA Nerve conduction studiesB Creatine kinase assayC Muscle biopsyD SMN1 gene analysisE All of the above
2 What is the most likely cause of this childrsquos symptoms Choose ONE answer ONLY from the followingA Congenital myotonic dystrophyB Duchenne muscular dystrophyC PraderminusWilli syndromeD Spinal muscular atrophyE Mitochondrial myopathy
3 What is the mode of inheritance of this disease Choose ONE answer ONLY from the followingA X-linked recessiveB Autosomal recessiveC Autosomal dominantD MitochondrialE Sporadic
Case 5A 13-year-old girl presents with a 3-week history of fever up to 40degC night sweats and headache She has a reduced appetite with some weight loss She has no other specific symptoms She was on holiday in China 7 months ago On examination she looks well and has a temperature of 387degC There is no lymphadenopathy and no rashes Examination is entirely normal
Results of investigations are as follows
haemoglobin 126 gdl (120ndash160)
total white blood cell count 132 times 109litre (43ndash108)
neutrophil count 115 times 109litre (25ndash75)
Platelet count 244 times 109litre (150ndash400)
Blood film neutrophilia with left shift
erythrocyte sedimentation rate 63 mmh (1ndash20)
c-reactive protein 219 mglitre (0ndash5)
Blood culture Streptococcus intermedius
from anaerobic bottle only
csf culture negative
Magnetic resonance imaging (MRI) of the brain shows acute frontal sinusitis with a large intracranial frontal extra-dural empyema (Figure 4)
1 Which of the following would be appropriate management Choose ONE answer ONLY from the followingA A 12-week course of intravenous antibioticsB Drainage of the frontal sinus followed by 2 weeks of
intravenous antibioticsC Drainage of the empyema followed by 2 weeks of
intravenous antibioticsD Drainage of the empyema and the frontal sinus
followed by 2 weeks of oral antibiotics
1151
1152
1153
1154
1155
1156
1157
1158
1159
1200
50ms 1mV
Figure 3 electromyogram recording from the patient Figure 4 Parasagittal section from mri scan of patient
Paediatrics and child health 184 204 copy 2008 elsevier ltd all rights reserved
self-assessment
E Drainage of the empyema and the frontal sinus followed by 8 weeks of intravenous antibiotics
2 Streptococcus intermedius is a potential pathogen in which of the following infections Choose ONE answer ONLY from the followingA Liver abscessB Urinary tract infectionC MeningitisD Thoracic empyemaE Pneumonia
3 Which of the following statements regarding lsquopyrexia of unknown originrsquo in children is false Choose ONE answer ONLY from the followingA Malignancy is the underlying pathology in 5ndash15 of
casesB An aetiology will be found in over 90 of casesC The most common cause is infectionD A rheumatological cause is found in 10ndash20 of casesE Familial Mediterranean fever can occur in children of
non-Mediterranean ethnicity
Answers
Case 11 AThe anion gap is a useful tool to differentiate the causes of a metabolic acidosis It is calculated by the equation
Anion gap = [Na K ] [Cl HCO ]3+ + minus minus+ minus +
It represents the effect of unmeasured anions on the plasma pH and is normally 10ndash18 mmollitre
2 CMicrovillus inclusion disease is a severe autosomal recessive enteropathy that is typically apparent within hours or days after birth It is the second most common cause of protracted diarrhoea in the newborn after infectious causes It is characterized by severe yellow watery diarrhoea and malabsorption due to hypoplasia andor atrophy of the villi of the small intestine secondary to an inherited defect in the brush border membrane This results in severe dehydration malnutrition and metabolic acidosis due to bicarbonate loss from the gut
3 CDiagnosis of microvillus inclusion disease is made on small bowel biopsy Electron microscopy findings are of intracellular brush border inclusions and densely packed apical cytoplasmic vesicular bodies indicating microvillous atrophy There is no cure Treatment is supportive with total parenteral nutrition and consideration of small bowel transplantation
Further reAding
Goulet O ruemmele f causes and management of intestinal failure
in children Gastroenterology 2006 130(suppl 1) s16ndash28
rhoads Jm Vogler rc lacey sr et al microvillus inclusion disease
In vitro jejunal electrolyte transport Gastroenterology 1991
100 811ndash817
Case 21 CGianottindashCrosti syndrome is a distinct self-limiting rash commonly associated with viral infections in children between 2 and 6 years of age It presents as multiple pink to redminusbrown papules or papulovesicles which may be pruritic and can become confluent Gianotti and Crosti initially described the exanthema as associated with hepatitis B virus and they termed it papular acrodermatitis of childhood It can occur in several viral diseases eg hepatitis A B and C coxsackie viruses and cytomegalovirus
2 BHepatitis is a syndrome characterized by inflammation or injury of liver cells which may develop into cell necrosis and subsequently fibrosis andor cirrhosis Biochemically there are raised liver enzymes The degree of transaminase elevation does not correlate with the severity of the disease process Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of viral hepatitis
3 DHepatitis B infection is transmitted via blood sexually or vertically Infection may be acute or chronic Diagnostic markers are the presence of surface antigen (HBsAg) and HBV DNA The presence of e antigen (HBeAg) indicates high infectivity Infected newborns have a 95 risk of becoming carriers this risk decreases with infection acquired later in childhood Approximately 15ndash25 of HBV carriers will die from cirrhosis or hepatocellular carcinoma Extrahepatic findings are more common in older children and include membranous glomerulonephritis and GianottiminusCrosti syndrome Fulminant hepatic failure occurs in severe cases resulting in persistent jaundice encephalopathy and coagulopathy Management includes counselling family members monitoring for ongoing liver disease and consideration of antiviral therapy
Further reAding
Brandt O abeck d Gianotti r Burgdorf W Gianotti crosti
syndrome J Am Acad Dermatol 2006 54 136ndash145
slowik mK Jhaveri r hepatitis B and c viruses in infants and
young children Semin Pediatr Infect Dis 2005 16 296ndash305
Case 31 CHypercalcaemia is uncommon in infancy The most common symptoms in this age group are irritability vomiting and constipation It may be a manifestation of Williams syndrome vitamin D or calcium excess as well as disorders associated with reduced bone formation such as hypophosphatasia or increased bone resorption such as malignancy Occasionally
Paediatrics and child health 184 205 copy 2008 elsevier ltd all rights reserved
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-
OccasiOnal review
11 Tallandini Ma scalembra c Kangaroo mother care and mother-
premature infant dyadic interaction Infant Ment Health J 2006 27
251ndash275
12 Ohgi s Fukuda M akiyama T Gima H effect of an early intervention
programme on low birthweight infants with cerebral injuries
J Paediatr Child Health 2004 40 689ndash695
13 Kaaresen Pi ronning Ja Ulvund se Dahl lB a randomized
controlled trial of the effectiveness of an early-intervention program
in reducing parenting stress after preterm birth Pediatrics 2006
118 e9ndash19
14 Melnyk BM Feinstein nF alpert-Gillis l et al reducing premature
infantsrsquo length of stay and improving parentsrsquo mental health
outcomes with the creating opportunities for parent empowerment
(cOPe) neonatal intensive care unit program a randomized
controlled trial Pediatrics 2006 118 e1414ndash1427
15 Jotzo M Poets cF Helping parents cope with the trauma of
premature birth an evaluation of a trauma-preventive psychological
intervention Pediatrics 2005 115 915ndash919
16 Pearson J andersen K evaluation of a program to promote positive
parenting in the neonatal intensive care unit Neonatal Netw 2001
20 43ndash48
17 roman l lindsay J Boger r et al Parent-to-parent support
initiated in the neonatal intensive care unit Res Nurs Health 1995
18 385ndash394
18 Meyer ec coll cTG lester BM Boukydis cFZ McDonough sM Oh w
Family-based intervention improves maternal psychological well-
being and feeding interaction of preterm infants Pediatrics 1994
93 241ndash246
PaeDiaTrics anD cHilD HealTH 184 19
19 Preyde M ardal F effectiveness of a parent ldquobuddyrdquo program for
mothers of very preterm infants in a neonatal intensive care unit
CMAJ 2003 168 969ndash973
20 Hurst i One size does not fit all Parentsrsquo evaluations of a support
program in a newborn intensive care nursery J Perinat Neonatal
Nurs 2006 20 252ndash261
Practice points
bull Parents of sick neonates experience significant distress and
exhibit higher levels of stress anxiety and depression than
parents of healthy infants
bull educational support emotional support and increased
motherndashinfant contact have been shown to promote maternal
well-being
bull emotional support for fathers has been largely neglected in
the research literature
bull Parents benefit from a choice of supportive facilities which
could include face-to-face sessions with health professionals
telephone support hospital visitation parent-to-parent
support and unit-based group support meetings
bull Parentsrsquo support needs can change during their infantrsquos
hospitalization and not all parents want or benefit from the
provision of additional information and emotional support in
the neonatal unit
9 copy 2008 elsevier ltd all rights reserved
Personal Practice
When should enteral feeds be started in preterm infantsnicholas D embleton
AbstractPaediatricians are regularly faced with the question of when best to start
enteral feeds in preterm infants this is important as longer term out-
come may be compromised by sub-optimal nutrition in early life clinical
factors that may affect the decision to start and the risk and benefits
are discussed
Keywords breast milk feeding nutrition parenteral nutrition
Key points in the history
Alice is lsquonutritionally vulnerablersquo and whilst this may not be immediately apparent it will affect her long term outcome Her energy stores are extremely limited and consist primarily of pro-tein She has less than 5 fat and little energy associated with stored glycogen She is losing about 1 gkgd protein equivalent so she needs at least that and a minimum of 50ndash60 kcalkg of energy just to maintain the status quo let alone grow
Her weight is on the 25th centile Review of any antenatal his-tory may reveal whether fetal growth was normal Fetal growth retardation can occur with a weight greater than 10th centile The presence of antenatal absent or reversed end diastolic flow in the umbilical artery indicates poor gut blood flow This increases the risk of necrotizing enterocolitis (NEC) and might suggest a more cautious approach to starting feeds1
She has no important cardiovascular problems but if she were hypotensive gut blood flow may be low There is no umbilical
Nicholas D Embleton BSC (Hons) MBBS (Hons) MD FRCPCH is Consultant in
Neonatal Medicine at Newcastle Neonatal Service Royal Victoria
Infirmary Newcastle upon Tyne NE1 4LP UK
Should you start feeds at a day of age
alice was born following spontaneous labour at 30 weeksrsquo
gestation she weighed 1300 g and is now 18 h old she was
briefly ventilated and then extubated to continuous positive
airway pressure 12 h ago in 35 oxygen she has had caffeine
citrate but still has intermittent episodes of self-correcting
apnoea she was commenced on iv 10 dextrose but this was
replaced by a parenteral amino acid solution (referred to as
lsquotPnrsquo) along with intralipid at 0900 this morning serum glucose
is 11 mmoll and blood pressure is 42 systolic
PaeDiatrics anD cHilD HealtH 184 20
arterial catheter in situ but there is no good evidence that this should delay the decision to start feeds Her glucose is high but this is quite common in a baby like this Could this be a sign of sepsis Caffeine does not affect the incidence of NEC2 The great-est risk factor for NEC in this case is prematurity
What else might be found on examination
Up until 24 h ago she was swallowing large amounts of amniotic fluid What will have changed since then
General examination should confirm peripheral perfusion lsquogestaltrsquo view (does she look lsquowellrsquo) and cardiovascular status lsquoBowel soundsrsquo are not usually helpful
The most important variable likely to affect gut perfusion is the arterial duct Precordial lsquoheaversquo and a loud murmur are sug-gestive but it is possible to have a significant ductal shunt in a baby with a normal examination Cardiac ultrasound will con-firm this diagnosis It might be better to treat a large shunt first with indometacin and to delay starting feeds for a further 24 h
It is not possible to assess gut perfusion clinically but normal perfusion elsewhere (adequate urine output usually indicates adequate renal perfusion) would be reassuring Most preterm babies have a few abdominal lsquoloopsrsquo visible but a distended abdomen with many palpable loops suggests ileus This might be secondary to sepsis or poor gut blood flow Preterm babies do not pass much meconium in the first 24ndash48 h
Balance of risks between starting and withholding feeds
Alice requires 35ndash4 gkgd of protein and 120 kcalkgd to grow3 This will initially be provided parenterally Delaying feeds increases the risk of gut villous atrophy and prolongs the need for lsquototal parenteral nutrition (TPN)rsquo TPN requires intravenous access and so increases the risk of sepsis and when prolonged use is required combined with the lack of enteral feeding may result in hepatic impairment
Delaying feeds may allow a gut that has been chronically under-perfused to re-establish more normal perfusion although normal gut endocrine function digestive enzyme upregulation and motility require a source of intraluminal nutrients1 A recent study suggested benefit from delaying the introduction of feeds4 but methodologi-cal problems exist5 Although a Cochrane meta-analysis suggested no benefit only two studies were included6 A large UK-based trial is examining the effect of early or late feeding in preterm infants who were born growth retarded following identification of antena-tal absent or reversed end diastolic flow in the umbilical artery7
When starting feeds what volume should be used
There are no good data to guide this decision We start with 24 mlkg (1 mlkgh) and then increase by this amount each day Most babies achieve full enteral feeds (ge150 mlkgd) by a week of age Feeding guidelines improve the outcome8 Measure-ment or assessment of gastric aspirates is not consistently useful in predicting subsequent feeding intolerance or development of NEC Aspirate volumes equivalent to or sometimes greater than the amount given in the preceding 1ndash2 h are usually normal Most aspirates have a greenish colour Thick bloody or intensely bile-stained aspirates require detailed assessment
0 copy 2008 elsevier ltd all rights reserved
Personal Practice
What else affects decisions and outcome
Feeding success is affected by sepsis and NEC Scrupulous atten-tion should be paid to hand washing and intravenous access and blood sampling should be minimized There is no good evidence to support the routine use of pro-kinetic agents or H2 blockers
The most important clinical intervention affecting the occur-rence of NEC is the use of breast milk9 All efforts should be directed at persuading parents of the benefits and supporting the process Some clinicians delay starting feeds for a further 24 h whilst expressed breast milk becomes available Donor breast milk might be equally efficacious10
RefeRenceS
1 Dorling J Kempley s leaf a Feeding growth restricted preterm
infants with abnormal antenatal Doppler results Arch Dis Child Fetal
Neonatal Ed 2005 90 F359ndash363
2 schmidt B roberts rs Davis P et al caffeine therapy for apnea of
prematurity N Engl J Med 2006 354 2112ndash2121
PaeDiatrics anD cHilD HealtH 184 20
3 embleton nD Pang n cooke rJ Postnatal malnutrition and growth
retardation an inevitable consequence of current recommendations
in preterm infants Pediatrics 2001 107 270ndash273
4 Berseth cl Bisquera Ja Paje VU Prolonging small feeding volumes
early in life decreases the incidence of necrotizing enterocolitis in
very low birth weight infants Pediatrics 2003 111 529ndash534
5 Menon G Boyle eM embleton nD et al introduction of enteral
feeds in preterm infants Pediatrics 2004 114 327ndash328
6 Kennedy Ka tyson Je chamnanvanikij s early versus delayed
initiation of progressive enteral feedings for parenterally fed low
birth weight or preterm infants Cochrane Database Syst Rev 2000
cD001970
7 wwwnpeuoxacukadept
8 Patole sK de Klerk n impact of standardised feeding regimens on
incidence of neonatal necrotising enterocolitis a systematic review
and meta-analysis of observational studies Arch Dis Child Fetal
Neonatal Ed 2005 90 F147ndash151
9 lucas a cole tJ Breast milk and neonatal necrotising enterocolitis
Lancet 1990 336 1519ndash1523
10 Boyd ca Quigley Ma Brocklehurst P Donor breast milk versus
infant formula for preterm infants systematic review and meta-
analysis Arch Dis Child Fetal Neonatal Ed 2007 92 F169ndash175
1 copy 2008 elsevier ltd all rights reserved
self-assessment
Case 1A term male infant born to consanguineous parents is assessed at 24 h of age due to poor feeding profuse yellow watery diar-rhoea and irritability He weighed 32 kg at birth and delivery was uneventful There was no polyhydramnios He has been breastfed since birth On examination he is pale with a non-tender but distended abdomen and reduced bowel sounds His weight is 275 kg and he looks dehydrated Examination is otherwise normal
Initial investigations (normal values in parentheses) showed
sodium 149 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 65 mmollitre (25ndash75)
creatinine 147 μmollitre (40ndash110)
chloride 119 mmollitre (95ndash105)
haemoglobin 172 gdl (140ndash200)
White blood cell count 80 times 109litre (100ndash260)
Platelet count 302 times 109litre (150ndash400)
arterial blood gas
ph 720 (730ndash745)
PcO2 23 kPa (46ndash60)
Bicarbonate 68 mmollitre (220ndash260)
Base excess minus186 mmollitre (minus20 to +20)
lactate 59 mmollitre (06ndash24)
An abdominal X-ray shows distended bowel loops with no intramural thickening or pneumoperitoneum (Figure 1)
He was given nil by mouth and received intravenous fluids and antibiotics His dehydration improved but the metabolic acidosis and diarrhoea persisted despite receiving no enteral feeds and the commencement of total parenteral nutrition Blood and stool cultures were negative
1 Which of the following best describes these results Choose ONE answer ONLY from the followingA Hypernatraemia hyperchloraemic metabolic acidosis
with increased anion gapB Hypernatraemia hyperchloraemic metabolic acidosis
with normal anion gap
Manish Sadarangani BM BCh MA MRCPCH is Clinical Research Fellow
at the Department of Paediatrics University of Oxford Centre for
Clinical Vaccinology and Tropical Medicine Churchill Hospital
Oxford OX3 7LJ UK
Shabna Rajapaksa MB BChir MA MRCPCH is Specialist Registrar in
Paediatrics at the Paediatric Intensive Care Unit John Radcliffe
Hospital Oxford OX3 9DU UK
Nicholas Mann MD FRCP FRCPCH DCH is Consultant Paediatrician at the
Department of Paediatrics Royal Berkshire Hospital Reading RG1
5AN UK
self-assessment
C Hypernatraemic dehydration and compensated metabolic acidosis
D Acute renal failureE Renal tubular acidosis
2 What is the likely diagnosis Choose ONE answer ONLY from the followingA Hirschsprung disease ndash long segmentB Cystic fibrosis with meconium ileusC Microvillus inclusion diseaseD Cowrsquos milk protein intoleranceE Lactose intolerance
3 What is the investigation of choice Choose ONE answer ONLY from the followingA Rectal biopsy with staining for acetylcholine receptorsB Immunoreactive trypsinC Gastrointestinal endoscopy and biopsyD Stool microscopy and cultureE Stool reducing substances
Case 2A 4-year-old boy presents with a 3 d history of jaundice and a florid rash He has had orange urine and there is no change in his stool colour His family originate from Kosovo and have lived in the UK for the last 8 years He has never left the UK There is no history of blood transfusion or sex-ual abuse The grandmother was recently diagnosed with hepatitis B
On examination he is well apyrexial and mildly jaundiced with cervical and axillary lymphadenopathy He has an exten-sive papular rash over the face extremities and trunk (Figure 2) There is 3 cm hepatomegaly with no splenomegaly or ascites Examination is otherwise normal
Figure 1 abdominal X-ray of baby
Paediatrics and child health 184 202 copy 2008 elsevier ltd all rights reserved
self-assessment
Initial investigations are as follows
haemoglobin 110 gdl (113ndash135)
White blood cell count 108 times 109litre (50ndash150)
Platelet count 278 times 109litre (150ndash400)
inr 10 (08ndash12)
aPt ratio 10 (08ndash13)
sodium 140 mmollitre (135ndash145)
Potassium 42 mmollitre (35ndash50)
Urea 56 mmollitre (25ndash75)
creatinine 65 μmollitre (45ndash120)
total bilirubin 66 μmollitre (0ndash15)
conjugated bilirubin 23 μmollitre (0ndash10)
alanine aminotransferase (alt) 2033 iUlitre (0ndash35)
alkaline phosphatase 987 iUlitre (71ndash234)
Gamma-glutamyl transferase (GGt) 870 iUlitre (0ndash51)
1 What is the name of this rash Choose ONE answer ONLY from the followingA Erythema multiformeB Erythema migransC GianottiminusCrosti syndromeD EczemaE Dermatitis herpetiformis
2 What is the most likely diagnosis Choose ONE Answer ONLY from the followingA Autoimmune hepatitisB Hepatitis BC Hepatitis DD Wilson diseaseE Alpha-1 antitrypsin deficiency
3 What is the best means of management Choose ONE answer ONLY from the followingA Isolation until the jaundice disappearsB ImmunosuppressionC Copper chelating agents and genetic counsellingD Patient and family education with consideration of
antiviral agentsE Liver transplantation
Case 3A 10-month-old boy presents with 3 weeks of vomiting and constipation ndash he is passing hard stools every 2ndash3 days He has fallen from the 9th to below the 04th centile in the last 6 weeks He passed meconium within the first 24 h of life On examina-tion he looks pale and there are some dysmorphic features ndash a short nose long philtrum and wide mouth He has normal heart sounds with a grade 3 ejection systolic murmur loudest at the upper right sternal edge Examination is otherwise normal
Initial investigations are as follows
haemoglobin 91 gdl (113ndash141)
total white blood cell count 124 times 109litre (60ndash170)
Platelet count 407 times 109litre (150ndash400)
sodium 144 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 78 mmollitre (25ndash75)
creatinine 78 μmollitre (45ndash120)
albumin 52 glitre (35ndash50)
corrected calcium 384 mmollitre (238ndash263)
Phosphate 167 mmollitre (099ndash157)
1 What is the most likely diagnosis Choose ONE answer ONLY from the followingA HyperparathyroidismB Acute leukaemiaC Williams syndromeD Hypervitaminosis DE Familial hypocalciuric hypercalcaemia
2 Which investigation would be most useful in establishing the diagnosis Choose ONE answer ONLY from the followingA Intact parathyroid hormone assayB Blood filmC Fluorescent in-situ hybridization for 7q1123 deletionD 25-hydroxyvitamin D assayE Urine calciumcreatinine ratio
3 Which of the following treatments would not be suitable for this patient Choose ONE answer ONLY from the followingA Low calcium dietB Normal saline infusionC FurosemideD CorticosteroidsE Bisphosphonates
Case 4A 10-week-old girl presents with a 2-day history of poor feed-ing Her mother has been concerned about weakness since birth She only has a flicker of movement in the arms none in the legs and has a weak cry She has been passing urine and opening her bowels normally She was born at full term by normal delivery and did not require any resuscitation at birth Normal fetal movements were felt antenatally and there was no polyhydramnios She is the first child of non- consanguineous parents and there is no significant family his-tory On examination she is alert and fixing and following appropriately She has a weak cry and a weak suck There is reduced central and peripheral tone with marked head lag
Figure 2 rash found on examination
Paediatrics and child health 184 203 copy 2008 elsevier ltd all rights reserved
self-assessment
Muscle power is grade 3 out of 5 in the arms and legs There is no muscle or tongue fasciculation and she has absent reflexes throughout The remainder of the examination is normal
Electromyogram shows irregular polyphasic motor unit potentials with marked instability consistent with a dener-vating and re-innervating process (Figure 3)
1 Which of the following additional investigations may be helpful Choose ONE answer ONLY from the followingA Nerve conduction studiesB Creatine kinase assayC Muscle biopsyD SMN1 gene analysisE All of the above
2 What is the most likely cause of this childrsquos symptoms Choose ONE answer ONLY from the followingA Congenital myotonic dystrophyB Duchenne muscular dystrophyC PraderminusWilli syndromeD Spinal muscular atrophyE Mitochondrial myopathy
3 What is the mode of inheritance of this disease Choose ONE answer ONLY from the followingA X-linked recessiveB Autosomal recessiveC Autosomal dominantD MitochondrialE Sporadic
Case 5A 13-year-old girl presents with a 3-week history of fever up to 40degC night sweats and headache She has a reduced appetite with some weight loss She has no other specific symptoms She was on holiday in China 7 months ago On examination she looks well and has a temperature of 387degC There is no lymphadenopathy and no rashes Examination is entirely normal
Results of investigations are as follows
haemoglobin 126 gdl (120ndash160)
total white blood cell count 132 times 109litre (43ndash108)
neutrophil count 115 times 109litre (25ndash75)
Platelet count 244 times 109litre (150ndash400)
Blood film neutrophilia with left shift
erythrocyte sedimentation rate 63 mmh (1ndash20)
c-reactive protein 219 mglitre (0ndash5)
Blood culture Streptococcus intermedius
from anaerobic bottle only
csf culture negative
Magnetic resonance imaging (MRI) of the brain shows acute frontal sinusitis with a large intracranial frontal extra-dural empyema (Figure 4)
1 Which of the following would be appropriate management Choose ONE answer ONLY from the followingA A 12-week course of intravenous antibioticsB Drainage of the frontal sinus followed by 2 weeks of
intravenous antibioticsC Drainage of the empyema followed by 2 weeks of
intravenous antibioticsD Drainage of the empyema and the frontal sinus
followed by 2 weeks of oral antibiotics
1151
1152
1153
1154
1155
1156
1157
1158
1159
1200
50ms 1mV
Figure 3 electromyogram recording from the patient Figure 4 Parasagittal section from mri scan of patient
Paediatrics and child health 184 204 copy 2008 elsevier ltd all rights reserved
self-assessment
E Drainage of the empyema and the frontal sinus followed by 8 weeks of intravenous antibiotics
2 Streptococcus intermedius is a potential pathogen in which of the following infections Choose ONE answer ONLY from the followingA Liver abscessB Urinary tract infectionC MeningitisD Thoracic empyemaE Pneumonia
3 Which of the following statements regarding lsquopyrexia of unknown originrsquo in children is false Choose ONE answer ONLY from the followingA Malignancy is the underlying pathology in 5ndash15 of
casesB An aetiology will be found in over 90 of casesC The most common cause is infectionD A rheumatological cause is found in 10ndash20 of casesE Familial Mediterranean fever can occur in children of
non-Mediterranean ethnicity
Answers
Case 11 AThe anion gap is a useful tool to differentiate the causes of a metabolic acidosis It is calculated by the equation
Anion gap = [Na K ] [Cl HCO ]3+ + minus minus+ minus +
It represents the effect of unmeasured anions on the plasma pH and is normally 10ndash18 mmollitre
2 CMicrovillus inclusion disease is a severe autosomal recessive enteropathy that is typically apparent within hours or days after birth It is the second most common cause of protracted diarrhoea in the newborn after infectious causes It is characterized by severe yellow watery diarrhoea and malabsorption due to hypoplasia andor atrophy of the villi of the small intestine secondary to an inherited defect in the brush border membrane This results in severe dehydration malnutrition and metabolic acidosis due to bicarbonate loss from the gut
3 CDiagnosis of microvillus inclusion disease is made on small bowel biopsy Electron microscopy findings are of intracellular brush border inclusions and densely packed apical cytoplasmic vesicular bodies indicating microvillous atrophy There is no cure Treatment is supportive with total parenteral nutrition and consideration of small bowel transplantation
Further reAding
Goulet O ruemmele f causes and management of intestinal failure
in children Gastroenterology 2006 130(suppl 1) s16ndash28
rhoads Jm Vogler rc lacey sr et al microvillus inclusion disease
In vitro jejunal electrolyte transport Gastroenterology 1991
100 811ndash817
Case 21 CGianottindashCrosti syndrome is a distinct self-limiting rash commonly associated with viral infections in children between 2 and 6 years of age It presents as multiple pink to redminusbrown papules or papulovesicles which may be pruritic and can become confluent Gianotti and Crosti initially described the exanthema as associated with hepatitis B virus and they termed it papular acrodermatitis of childhood It can occur in several viral diseases eg hepatitis A B and C coxsackie viruses and cytomegalovirus
2 BHepatitis is a syndrome characterized by inflammation or injury of liver cells which may develop into cell necrosis and subsequently fibrosis andor cirrhosis Biochemically there are raised liver enzymes The degree of transaminase elevation does not correlate with the severity of the disease process Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of viral hepatitis
3 DHepatitis B infection is transmitted via blood sexually or vertically Infection may be acute or chronic Diagnostic markers are the presence of surface antigen (HBsAg) and HBV DNA The presence of e antigen (HBeAg) indicates high infectivity Infected newborns have a 95 risk of becoming carriers this risk decreases with infection acquired later in childhood Approximately 15ndash25 of HBV carriers will die from cirrhosis or hepatocellular carcinoma Extrahepatic findings are more common in older children and include membranous glomerulonephritis and GianottiminusCrosti syndrome Fulminant hepatic failure occurs in severe cases resulting in persistent jaundice encephalopathy and coagulopathy Management includes counselling family members monitoring for ongoing liver disease and consideration of antiviral therapy
Further reAding
Brandt O abeck d Gianotti r Burgdorf W Gianotti crosti
syndrome J Am Acad Dermatol 2006 54 136ndash145
slowik mK Jhaveri r hepatitis B and c viruses in infants and
young children Semin Pediatr Infect Dis 2005 16 296ndash305
Case 31 CHypercalcaemia is uncommon in infancy The most common symptoms in this age group are irritability vomiting and constipation It may be a manifestation of Williams syndrome vitamin D or calcium excess as well as disorders associated with reduced bone formation such as hypophosphatasia or increased bone resorption such as malignancy Occasionally
Paediatrics and child health 184 205 copy 2008 elsevier ltd all rights reserved
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-
Personal Practice
When should enteral feeds be started in preterm infantsnicholas D embleton
AbstractPaediatricians are regularly faced with the question of when best to start
enteral feeds in preterm infants this is important as longer term out-
come may be compromised by sub-optimal nutrition in early life clinical
factors that may affect the decision to start and the risk and benefits
are discussed
Keywords breast milk feeding nutrition parenteral nutrition
Key points in the history
Alice is lsquonutritionally vulnerablersquo and whilst this may not be immediately apparent it will affect her long term outcome Her energy stores are extremely limited and consist primarily of pro-tein She has less than 5 fat and little energy associated with stored glycogen She is losing about 1 gkgd protein equivalent so she needs at least that and a minimum of 50ndash60 kcalkg of energy just to maintain the status quo let alone grow
Her weight is on the 25th centile Review of any antenatal his-tory may reveal whether fetal growth was normal Fetal growth retardation can occur with a weight greater than 10th centile The presence of antenatal absent or reversed end diastolic flow in the umbilical artery indicates poor gut blood flow This increases the risk of necrotizing enterocolitis (NEC) and might suggest a more cautious approach to starting feeds1
She has no important cardiovascular problems but if she were hypotensive gut blood flow may be low There is no umbilical
Nicholas D Embleton BSC (Hons) MBBS (Hons) MD FRCPCH is Consultant in
Neonatal Medicine at Newcastle Neonatal Service Royal Victoria
Infirmary Newcastle upon Tyne NE1 4LP UK
Should you start feeds at a day of age
alice was born following spontaneous labour at 30 weeksrsquo
gestation she weighed 1300 g and is now 18 h old she was
briefly ventilated and then extubated to continuous positive
airway pressure 12 h ago in 35 oxygen she has had caffeine
citrate but still has intermittent episodes of self-correcting
apnoea she was commenced on iv 10 dextrose but this was
replaced by a parenteral amino acid solution (referred to as
lsquotPnrsquo) along with intralipid at 0900 this morning serum glucose
is 11 mmoll and blood pressure is 42 systolic
PaeDiatrics anD cHilD HealtH 184 20
arterial catheter in situ but there is no good evidence that this should delay the decision to start feeds Her glucose is high but this is quite common in a baby like this Could this be a sign of sepsis Caffeine does not affect the incidence of NEC2 The great-est risk factor for NEC in this case is prematurity
What else might be found on examination
Up until 24 h ago she was swallowing large amounts of amniotic fluid What will have changed since then
General examination should confirm peripheral perfusion lsquogestaltrsquo view (does she look lsquowellrsquo) and cardiovascular status lsquoBowel soundsrsquo are not usually helpful
The most important variable likely to affect gut perfusion is the arterial duct Precordial lsquoheaversquo and a loud murmur are sug-gestive but it is possible to have a significant ductal shunt in a baby with a normal examination Cardiac ultrasound will con-firm this diagnosis It might be better to treat a large shunt first with indometacin and to delay starting feeds for a further 24 h
It is not possible to assess gut perfusion clinically but normal perfusion elsewhere (adequate urine output usually indicates adequate renal perfusion) would be reassuring Most preterm babies have a few abdominal lsquoloopsrsquo visible but a distended abdomen with many palpable loops suggests ileus This might be secondary to sepsis or poor gut blood flow Preterm babies do not pass much meconium in the first 24ndash48 h
Balance of risks between starting and withholding feeds
Alice requires 35ndash4 gkgd of protein and 120 kcalkgd to grow3 This will initially be provided parenterally Delaying feeds increases the risk of gut villous atrophy and prolongs the need for lsquototal parenteral nutrition (TPN)rsquo TPN requires intravenous access and so increases the risk of sepsis and when prolonged use is required combined with the lack of enteral feeding may result in hepatic impairment
Delaying feeds may allow a gut that has been chronically under-perfused to re-establish more normal perfusion although normal gut endocrine function digestive enzyme upregulation and motility require a source of intraluminal nutrients1 A recent study suggested benefit from delaying the introduction of feeds4 but methodologi-cal problems exist5 Although a Cochrane meta-analysis suggested no benefit only two studies were included6 A large UK-based trial is examining the effect of early or late feeding in preterm infants who were born growth retarded following identification of antena-tal absent or reversed end diastolic flow in the umbilical artery7
When starting feeds what volume should be used
There are no good data to guide this decision We start with 24 mlkg (1 mlkgh) and then increase by this amount each day Most babies achieve full enteral feeds (ge150 mlkgd) by a week of age Feeding guidelines improve the outcome8 Measure-ment or assessment of gastric aspirates is not consistently useful in predicting subsequent feeding intolerance or development of NEC Aspirate volumes equivalent to or sometimes greater than the amount given in the preceding 1ndash2 h are usually normal Most aspirates have a greenish colour Thick bloody or intensely bile-stained aspirates require detailed assessment
0 copy 2008 elsevier ltd all rights reserved
Personal Practice
What else affects decisions and outcome
Feeding success is affected by sepsis and NEC Scrupulous atten-tion should be paid to hand washing and intravenous access and blood sampling should be minimized There is no good evidence to support the routine use of pro-kinetic agents or H2 blockers
The most important clinical intervention affecting the occur-rence of NEC is the use of breast milk9 All efforts should be directed at persuading parents of the benefits and supporting the process Some clinicians delay starting feeds for a further 24 h whilst expressed breast milk becomes available Donor breast milk might be equally efficacious10
RefeRenceS
1 Dorling J Kempley s leaf a Feeding growth restricted preterm
infants with abnormal antenatal Doppler results Arch Dis Child Fetal
Neonatal Ed 2005 90 F359ndash363
2 schmidt B roberts rs Davis P et al caffeine therapy for apnea of
prematurity N Engl J Med 2006 354 2112ndash2121
PaeDiatrics anD cHilD HealtH 184 20
3 embleton nD Pang n cooke rJ Postnatal malnutrition and growth
retardation an inevitable consequence of current recommendations
in preterm infants Pediatrics 2001 107 270ndash273
4 Berseth cl Bisquera Ja Paje VU Prolonging small feeding volumes
early in life decreases the incidence of necrotizing enterocolitis in
very low birth weight infants Pediatrics 2003 111 529ndash534
5 Menon G Boyle eM embleton nD et al introduction of enteral
feeds in preterm infants Pediatrics 2004 114 327ndash328
6 Kennedy Ka tyson Je chamnanvanikij s early versus delayed
initiation of progressive enteral feedings for parenterally fed low
birth weight or preterm infants Cochrane Database Syst Rev 2000
cD001970
7 wwwnpeuoxacukadept
8 Patole sK de Klerk n impact of standardised feeding regimens on
incidence of neonatal necrotising enterocolitis a systematic review
and meta-analysis of observational studies Arch Dis Child Fetal
Neonatal Ed 2005 90 F147ndash151
9 lucas a cole tJ Breast milk and neonatal necrotising enterocolitis
Lancet 1990 336 1519ndash1523
10 Boyd ca Quigley Ma Brocklehurst P Donor breast milk versus
infant formula for preterm infants systematic review and meta-
analysis Arch Dis Child Fetal Neonatal Ed 2007 92 F169ndash175
1 copy 2008 elsevier ltd all rights reserved
self-assessment
Case 1A term male infant born to consanguineous parents is assessed at 24 h of age due to poor feeding profuse yellow watery diar-rhoea and irritability He weighed 32 kg at birth and delivery was uneventful There was no polyhydramnios He has been breastfed since birth On examination he is pale with a non-tender but distended abdomen and reduced bowel sounds His weight is 275 kg and he looks dehydrated Examination is otherwise normal
Initial investigations (normal values in parentheses) showed
sodium 149 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 65 mmollitre (25ndash75)
creatinine 147 μmollitre (40ndash110)
chloride 119 mmollitre (95ndash105)
haemoglobin 172 gdl (140ndash200)
White blood cell count 80 times 109litre (100ndash260)
Platelet count 302 times 109litre (150ndash400)
arterial blood gas
ph 720 (730ndash745)
PcO2 23 kPa (46ndash60)
Bicarbonate 68 mmollitre (220ndash260)
Base excess minus186 mmollitre (minus20 to +20)
lactate 59 mmollitre (06ndash24)
An abdominal X-ray shows distended bowel loops with no intramural thickening or pneumoperitoneum (Figure 1)
He was given nil by mouth and received intravenous fluids and antibiotics His dehydration improved but the metabolic acidosis and diarrhoea persisted despite receiving no enteral feeds and the commencement of total parenteral nutrition Blood and stool cultures were negative
1 Which of the following best describes these results Choose ONE answer ONLY from the followingA Hypernatraemia hyperchloraemic metabolic acidosis
with increased anion gapB Hypernatraemia hyperchloraemic metabolic acidosis
with normal anion gap
Manish Sadarangani BM BCh MA MRCPCH is Clinical Research Fellow
at the Department of Paediatrics University of Oxford Centre for
Clinical Vaccinology and Tropical Medicine Churchill Hospital
Oxford OX3 7LJ UK
Shabna Rajapaksa MB BChir MA MRCPCH is Specialist Registrar in
Paediatrics at the Paediatric Intensive Care Unit John Radcliffe
Hospital Oxford OX3 9DU UK
Nicholas Mann MD FRCP FRCPCH DCH is Consultant Paediatrician at the
Department of Paediatrics Royal Berkshire Hospital Reading RG1
5AN UK
self-assessment
C Hypernatraemic dehydration and compensated metabolic acidosis
D Acute renal failureE Renal tubular acidosis
2 What is the likely diagnosis Choose ONE answer ONLY from the followingA Hirschsprung disease ndash long segmentB Cystic fibrosis with meconium ileusC Microvillus inclusion diseaseD Cowrsquos milk protein intoleranceE Lactose intolerance
3 What is the investigation of choice Choose ONE answer ONLY from the followingA Rectal biopsy with staining for acetylcholine receptorsB Immunoreactive trypsinC Gastrointestinal endoscopy and biopsyD Stool microscopy and cultureE Stool reducing substances
Case 2A 4-year-old boy presents with a 3 d history of jaundice and a florid rash He has had orange urine and there is no change in his stool colour His family originate from Kosovo and have lived in the UK for the last 8 years He has never left the UK There is no history of blood transfusion or sex-ual abuse The grandmother was recently diagnosed with hepatitis B
On examination he is well apyrexial and mildly jaundiced with cervical and axillary lymphadenopathy He has an exten-sive papular rash over the face extremities and trunk (Figure 2) There is 3 cm hepatomegaly with no splenomegaly or ascites Examination is otherwise normal
Figure 1 abdominal X-ray of baby
Paediatrics and child health 184 202 copy 2008 elsevier ltd all rights reserved
self-assessment
Initial investigations are as follows
haemoglobin 110 gdl (113ndash135)
White blood cell count 108 times 109litre (50ndash150)
Platelet count 278 times 109litre (150ndash400)
inr 10 (08ndash12)
aPt ratio 10 (08ndash13)
sodium 140 mmollitre (135ndash145)
Potassium 42 mmollitre (35ndash50)
Urea 56 mmollitre (25ndash75)
creatinine 65 μmollitre (45ndash120)
total bilirubin 66 μmollitre (0ndash15)
conjugated bilirubin 23 μmollitre (0ndash10)
alanine aminotransferase (alt) 2033 iUlitre (0ndash35)
alkaline phosphatase 987 iUlitre (71ndash234)
Gamma-glutamyl transferase (GGt) 870 iUlitre (0ndash51)
1 What is the name of this rash Choose ONE answer ONLY from the followingA Erythema multiformeB Erythema migransC GianottiminusCrosti syndromeD EczemaE Dermatitis herpetiformis
2 What is the most likely diagnosis Choose ONE Answer ONLY from the followingA Autoimmune hepatitisB Hepatitis BC Hepatitis DD Wilson diseaseE Alpha-1 antitrypsin deficiency
3 What is the best means of management Choose ONE answer ONLY from the followingA Isolation until the jaundice disappearsB ImmunosuppressionC Copper chelating agents and genetic counsellingD Patient and family education with consideration of
antiviral agentsE Liver transplantation
Case 3A 10-month-old boy presents with 3 weeks of vomiting and constipation ndash he is passing hard stools every 2ndash3 days He has fallen from the 9th to below the 04th centile in the last 6 weeks He passed meconium within the first 24 h of life On examina-tion he looks pale and there are some dysmorphic features ndash a short nose long philtrum and wide mouth He has normal heart sounds with a grade 3 ejection systolic murmur loudest at the upper right sternal edge Examination is otherwise normal
Initial investigations are as follows
haemoglobin 91 gdl (113ndash141)
total white blood cell count 124 times 109litre (60ndash170)
Platelet count 407 times 109litre (150ndash400)
sodium 144 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 78 mmollitre (25ndash75)
creatinine 78 μmollitre (45ndash120)
albumin 52 glitre (35ndash50)
corrected calcium 384 mmollitre (238ndash263)
Phosphate 167 mmollitre (099ndash157)
1 What is the most likely diagnosis Choose ONE answer ONLY from the followingA HyperparathyroidismB Acute leukaemiaC Williams syndromeD Hypervitaminosis DE Familial hypocalciuric hypercalcaemia
2 Which investigation would be most useful in establishing the diagnosis Choose ONE answer ONLY from the followingA Intact parathyroid hormone assayB Blood filmC Fluorescent in-situ hybridization for 7q1123 deletionD 25-hydroxyvitamin D assayE Urine calciumcreatinine ratio
3 Which of the following treatments would not be suitable for this patient Choose ONE answer ONLY from the followingA Low calcium dietB Normal saline infusionC FurosemideD CorticosteroidsE Bisphosphonates
Case 4A 10-week-old girl presents with a 2-day history of poor feed-ing Her mother has been concerned about weakness since birth She only has a flicker of movement in the arms none in the legs and has a weak cry She has been passing urine and opening her bowels normally She was born at full term by normal delivery and did not require any resuscitation at birth Normal fetal movements were felt antenatally and there was no polyhydramnios She is the first child of non- consanguineous parents and there is no significant family his-tory On examination she is alert and fixing and following appropriately She has a weak cry and a weak suck There is reduced central and peripheral tone with marked head lag
Figure 2 rash found on examination
Paediatrics and child health 184 203 copy 2008 elsevier ltd all rights reserved
self-assessment
Muscle power is grade 3 out of 5 in the arms and legs There is no muscle or tongue fasciculation and she has absent reflexes throughout The remainder of the examination is normal
Electromyogram shows irregular polyphasic motor unit potentials with marked instability consistent with a dener-vating and re-innervating process (Figure 3)
1 Which of the following additional investigations may be helpful Choose ONE answer ONLY from the followingA Nerve conduction studiesB Creatine kinase assayC Muscle biopsyD SMN1 gene analysisE All of the above
2 What is the most likely cause of this childrsquos symptoms Choose ONE answer ONLY from the followingA Congenital myotonic dystrophyB Duchenne muscular dystrophyC PraderminusWilli syndromeD Spinal muscular atrophyE Mitochondrial myopathy
3 What is the mode of inheritance of this disease Choose ONE answer ONLY from the followingA X-linked recessiveB Autosomal recessiveC Autosomal dominantD MitochondrialE Sporadic
Case 5A 13-year-old girl presents with a 3-week history of fever up to 40degC night sweats and headache She has a reduced appetite with some weight loss She has no other specific symptoms She was on holiday in China 7 months ago On examination she looks well and has a temperature of 387degC There is no lymphadenopathy and no rashes Examination is entirely normal
Results of investigations are as follows
haemoglobin 126 gdl (120ndash160)
total white blood cell count 132 times 109litre (43ndash108)
neutrophil count 115 times 109litre (25ndash75)
Platelet count 244 times 109litre (150ndash400)
Blood film neutrophilia with left shift
erythrocyte sedimentation rate 63 mmh (1ndash20)
c-reactive protein 219 mglitre (0ndash5)
Blood culture Streptococcus intermedius
from anaerobic bottle only
csf culture negative
Magnetic resonance imaging (MRI) of the brain shows acute frontal sinusitis with a large intracranial frontal extra-dural empyema (Figure 4)
1 Which of the following would be appropriate management Choose ONE answer ONLY from the followingA A 12-week course of intravenous antibioticsB Drainage of the frontal sinus followed by 2 weeks of
intravenous antibioticsC Drainage of the empyema followed by 2 weeks of
intravenous antibioticsD Drainage of the empyema and the frontal sinus
followed by 2 weeks of oral antibiotics
1151
1152
1153
1154
1155
1156
1157
1158
1159
1200
50ms 1mV
Figure 3 electromyogram recording from the patient Figure 4 Parasagittal section from mri scan of patient
Paediatrics and child health 184 204 copy 2008 elsevier ltd all rights reserved
self-assessment
E Drainage of the empyema and the frontal sinus followed by 8 weeks of intravenous antibiotics
2 Streptococcus intermedius is a potential pathogen in which of the following infections Choose ONE answer ONLY from the followingA Liver abscessB Urinary tract infectionC MeningitisD Thoracic empyemaE Pneumonia
3 Which of the following statements regarding lsquopyrexia of unknown originrsquo in children is false Choose ONE answer ONLY from the followingA Malignancy is the underlying pathology in 5ndash15 of
casesB An aetiology will be found in over 90 of casesC The most common cause is infectionD A rheumatological cause is found in 10ndash20 of casesE Familial Mediterranean fever can occur in children of
non-Mediterranean ethnicity
Answers
Case 11 AThe anion gap is a useful tool to differentiate the causes of a metabolic acidosis It is calculated by the equation
Anion gap = [Na K ] [Cl HCO ]3+ + minus minus+ minus +
It represents the effect of unmeasured anions on the plasma pH and is normally 10ndash18 mmollitre
2 CMicrovillus inclusion disease is a severe autosomal recessive enteropathy that is typically apparent within hours or days after birth It is the second most common cause of protracted diarrhoea in the newborn after infectious causes It is characterized by severe yellow watery diarrhoea and malabsorption due to hypoplasia andor atrophy of the villi of the small intestine secondary to an inherited defect in the brush border membrane This results in severe dehydration malnutrition and metabolic acidosis due to bicarbonate loss from the gut
3 CDiagnosis of microvillus inclusion disease is made on small bowel biopsy Electron microscopy findings are of intracellular brush border inclusions and densely packed apical cytoplasmic vesicular bodies indicating microvillous atrophy There is no cure Treatment is supportive with total parenteral nutrition and consideration of small bowel transplantation
Further reAding
Goulet O ruemmele f causes and management of intestinal failure
in children Gastroenterology 2006 130(suppl 1) s16ndash28
rhoads Jm Vogler rc lacey sr et al microvillus inclusion disease
In vitro jejunal electrolyte transport Gastroenterology 1991
100 811ndash817
Case 21 CGianottindashCrosti syndrome is a distinct self-limiting rash commonly associated with viral infections in children between 2 and 6 years of age It presents as multiple pink to redminusbrown papules or papulovesicles which may be pruritic and can become confluent Gianotti and Crosti initially described the exanthema as associated with hepatitis B virus and they termed it papular acrodermatitis of childhood It can occur in several viral diseases eg hepatitis A B and C coxsackie viruses and cytomegalovirus
2 BHepatitis is a syndrome characterized by inflammation or injury of liver cells which may develop into cell necrosis and subsequently fibrosis andor cirrhosis Biochemically there are raised liver enzymes The degree of transaminase elevation does not correlate with the severity of the disease process Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of viral hepatitis
3 DHepatitis B infection is transmitted via blood sexually or vertically Infection may be acute or chronic Diagnostic markers are the presence of surface antigen (HBsAg) and HBV DNA The presence of e antigen (HBeAg) indicates high infectivity Infected newborns have a 95 risk of becoming carriers this risk decreases with infection acquired later in childhood Approximately 15ndash25 of HBV carriers will die from cirrhosis or hepatocellular carcinoma Extrahepatic findings are more common in older children and include membranous glomerulonephritis and GianottiminusCrosti syndrome Fulminant hepatic failure occurs in severe cases resulting in persistent jaundice encephalopathy and coagulopathy Management includes counselling family members monitoring for ongoing liver disease and consideration of antiviral therapy
Further reAding
Brandt O abeck d Gianotti r Burgdorf W Gianotti crosti
syndrome J Am Acad Dermatol 2006 54 136ndash145
slowik mK Jhaveri r hepatitis B and c viruses in infants and
young children Semin Pediatr Infect Dis 2005 16 296ndash305
Case 31 CHypercalcaemia is uncommon in infancy The most common symptoms in this age group are irritability vomiting and constipation It may be a manifestation of Williams syndrome vitamin D or calcium excess as well as disorders associated with reduced bone formation such as hypophosphatasia or increased bone resorption such as malignancy Occasionally
Paediatrics and child health 184 205 copy 2008 elsevier ltd all rights reserved
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-
Personal Practice
What else affects decisions and outcome
Feeding success is affected by sepsis and NEC Scrupulous atten-tion should be paid to hand washing and intravenous access and blood sampling should be minimized There is no good evidence to support the routine use of pro-kinetic agents or H2 blockers
The most important clinical intervention affecting the occur-rence of NEC is the use of breast milk9 All efforts should be directed at persuading parents of the benefits and supporting the process Some clinicians delay starting feeds for a further 24 h whilst expressed breast milk becomes available Donor breast milk might be equally efficacious10
RefeRenceS
1 Dorling J Kempley s leaf a Feeding growth restricted preterm
infants with abnormal antenatal Doppler results Arch Dis Child Fetal
Neonatal Ed 2005 90 F359ndash363
2 schmidt B roberts rs Davis P et al caffeine therapy for apnea of
prematurity N Engl J Med 2006 354 2112ndash2121
PaeDiatrics anD cHilD HealtH 184 20
3 embleton nD Pang n cooke rJ Postnatal malnutrition and growth
retardation an inevitable consequence of current recommendations
in preterm infants Pediatrics 2001 107 270ndash273
4 Berseth cl Bisquera Ja Paje VU Prolonging small feeding volumes
early in life decreases the incidence of necrotizing enterocolitis in
very low birth weight infants Pediatrics 2003 111 529ndash534
5 Menon G Boyle eM embleton nD et al introduction of enteral
feeds in preterm infants Pediatrics 2004 114 327ndash328
6 Kennedy Ka tyson Je chamnanvanikij s early versus delayed
initiation of progressive enteral feedings for parenterally fed low
birth weight or preterm infants Cochrane Database Syst Rev 2000
cD001970
7 wwwnpeuoxacukadept
8 Patole sK de Klerk n impact of standardised feeding regimens on
incidence of neonatal necrotising enterocolitis a systematic review
and meta-analysis of observational studies Arch Dis Child Fetal
Neonatal Ed 2005 90 F147ndash151
9 lucas a cole tJ Breast milk and neonatal necrotising enterocolitis
Lancet 1990 336 1519ndash1523
10 Boyd ca Quigley Ma Brocklehurst P Donor breast milk versus
infant formula for preterm infants systematic review and meta-
analysis Arch Dis Child Fetal Neonatal Ed 2007 92 F169ndash175
1 copy 2008 elsevier ltd all rights reserved
self-assessment
Case 1A term male infant born to consanguineous parents is assessed at 24 h of age due to poor feeding profuse yellow watery diar-rhoea and irritability He weighed 32 kg at birth and delivery was uneventful There was no polyhydramnios He has been breastfed since birth On examination he is pale with a non-tender but distended abdomen and reduced bowel sounds His weight is 275 kg and he looks dehydrated Examination is otherwise normal
Initial investigations (normal values in parentheses) showed
sodium 149 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 65 mmollitre (25ndash75)
creatinine 147 μmollitre (40ndash110)
chloride 119 mmollitre (95ndash105)
haemoglobin 172 gdl (140ndash200)
White blood cell count 80 times 109litre (100ndash260)
Platelet count 302 times 109litre (150ndash400)
arterial blood gas
ph 720 (730ndash745)
PcO2 23 kPa (46ndash60)
Bicarbonate 68 mmollitre (220ndash260)
Base excess minus186 mmollitre (minus20 to +20)
lactate 59 mmollitre (06ndash24)
An abdominal X-ray shows distended bowel loops with no intramural thickening or pneumoperitoneum (Figure 1)
He was given nil by mouth and received intravenous fluids and antibiotics His dehydration improved but the metabolic acidosis and diarrhoea persisted despite receiving no enteral feeds and the commencement of total parenteral nutrition Blood and stool cultures were negative
1 Which of the following best describes these results Choose ONE answer ONLY from the followingA Hypernatraemia hyperchloraemic metabolic acidosis
with increased anion gapB Hypernatraemia hyperchloraemic metabolic acidosis
with normal anion gap
Manish Sadarangani BM BCh MA MRCPCH is Clinical Research Fellow
at the Department of Paediatrics University of Oxford Centre for
Clinical Vaccinology and Tropical Medicine Churchill Hospital
Oxford OX3 7LJ UK
Shabna Rajapaksa MB BChir MA MRCPCH is Specialist Registrar in
Paediatrics at the Paediatric Intensive Care Unit John Radcliffe
Hospital Oxford OX3 9DU UK
Nicholas Mann MD FRCP FRCPCH DCH is Consultant Paediatrician at the
Department of Paediatrics Royal Berkshire Hospital Reading RG1
5AN UK
self-assessment
C Hypernatraemic dehydration and compensated metabolic acidosis
D Acute renal failureE Renal tubular acidosis
2 What is the likely diagnosis Choose ONE answer ONLY from the followingA Hirschsprung disease ndash long segmentB Cystic fibrosis with meconium ileusC Microvillus inclusion diseaseD Cowrsquos milk protein intoleranceE Lactose intolerance
3 What is the investigation of choice Choose ONE answer ONLY from the followingA Rectal biopsy with staining for acetylcholine receptorsB Immunoreactive trypsinC Gastrointestinal endoscopy and biopsyD Stool microscopy and cultureE Stool reducing substances
Case 2A 4-year-old boy presents with a 3 d history of jaundice and a florid rash He has had orange urine and there is no change in his stool colour His family originate from Kosovo and have lived in the UK for the last 8 years He has never left the UK There is no history of blood transfusion or sex-ual abuse The grandmother was recently diagnosed with hepatitis B
On examination he is well apyrexial and mildly jaundiced with cervical and axillary lymphadenopathy He has an exten-sive papular rash over the face extremities and trunk (Figure 2) There is 3 cm hepatomegaly with no splenomegaly or ascites Examination is otherwise normal
Figure 1 abdominal X-ray of baby
Paediatrics and child health 184 202 copy 2008 elsevier ltd all rights reserved
self-assessment
Initial investigations are as follows
haemoglobin 110 gdl (113ndash135)
White blood cell count 108 times 109litre (50ndash150)
Platelet count 278 times 109litre (150ndash400)
inr 10 (08ndash12)
aPt ratio 10 (08ndash13)
sodium 140 mmollitre (135ndash145)
Potassium 42 mmollitre (35ndash50)
Urea 56 mmollitre (25ndash75)
creatinine 65 μmollitre (45ndash120)
total bilirubin 66 μmollitre (0ndash15)
conjugated bilirubin 23 μmollitre (0ndash10)
alanine aminotransferase (alt) 2033 iUlitre (0ndash35)
alkaline phosphatase 987 iUlitre (71ndash234)
Gamma-glutamyl transferase (GGt) 870 iUlitre (0ndash51)
1 What is the name of this rash Choose ONE answer ONLY from the followingA Erythema multiformeB Erythema migransC GianottiminusCrosti syndromeD EczemaE Dermatitis herpetiformis
2 What is the most likely diagnosis Choose ONE Answer ONLY from the followingA Autoimmune hepatitisB Hepatitis BC Hepatitis DD Wilson diseaseE Alpha-1 antitrypsin deficiency
3 What is the best means of management Choose ONE answer ONLY from the followingA Isolation until the jaundice disappearsB ImmunosuppressionC Copper chelating agents and genetic counsellingD Patient and family education with consideration of
antiviral agentsE Liver transplantation
Case 3A 10-month-old boy presents with 3 weeks of vomiting and constipation ndash he is passing hard stools every 2ndash3 days He has fallen from the 9th to below the 04th centile in the last 6 weeks He passed meconium within the first 24 h of life On examina-tion he looks pale and there are some dysmorphic features ndash a short nose long philtrum and wide mouth He has normal heart sounds with a grade 3 ejection systolic murmur loudest at the upper right sternal edge Examination is otherwise normal
Initial investigations are as follows
haemoglobin 91 gdl (113ndash141)
total white blood cell count 124 times 109litre (60ndash170)
Platelet count 407 times 109litre (150ndash400)
sodium 144 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 78 mmollitre (25ndash75)
creatinine 78 μmollitre (45ndash120)
albumin 52 glitre (35ndash50)
corrected calcium 384 mmollitre (238ndash263)
Phosphate 167 mmollitre (099ndash157)
1 What is the most likely diagnosis Choose ONE answer ONLY from the followingA HyperparathyroidismB Acute leukaemiaC Williams syndromeD Hypervitaminosis DE Familial hypocalciuric hypercalcaemia
2 Which investigation would be most useful in establishing the diagnosis Choose ONE answer ONLY from the followingA Intact parathyroid hormone assayB Blood filmC Fluorescent in-situ hybridization for 7q1123 deletionD 25-hydroxyvitamin D assayE Urine calciumcreatinine ratio
3 Which of the following treatments would not be suitable for this patient Choose ONE answer ONLY from the followingA Low calcium dietB Normal saline infusionC FurosemideD CorticosteroidsE Bisphosphonates
Case 4A 10-week-old girl presents with a 2-day history of poor feed-ing Her mother has been concerned about weakness since birth She only has a flicker of movement in the arms none in the legs and has a weak cry She has been passing urine and opening her bowels normally She was born at full term by normal delivery and did not require any resuscitation at birth Normal fetal movements were felt antenatally and there was no polyhydramnios She is the first child of non- consanguineous parents and there is no significant family his-tory On examination she is alert and fixing and following appropriately She has a weak cry and a weak suck There is reduced central and peripheral tone with marked head lag
Figure 2 rash found on examination
Paediatrics and child health 184 203 copy 2008 elsevier ltd all rights reserved
self-assessment
Muscle power is grade 3 out of 5 in the arms and legs There is no muscle or tongue fasciculation and she has absent reflexes throughout The remainder of the examination is normal
Electromyogram shows irregular polyphasic motor unit potentials with marked instability consistent with a dener-vating and re-innervating process (Figure 3)
1 Which of the following additional investigations may be helpful Choose ONE answer ONLY from the followingA Nerve conduction studiesB Creatine kinase assayC Muscle biopsyD SMN1 gene analysisE All of the above
2 What is the most likely cause of this childrsquos symptoms Choose ONE answer ONLY from the followingA Congenital myotonic dystrophyB Duchenne muscular dystrophyC PraderminusWilli syndromeD Spinal muscular atrophyE Mitochondrial myopathy
3 What is the mode of inheritance of this disease Choose ONE answer ONLY from the followingA X-linked recessiveB Autosomal recessiveC Autosomal dominantD MitochondrialE Sporadic
Case 5A 13-year-old girl presents with a 3-week history of fever up to 40degC night sweats and headache She has a reduced appetite with some weight loss She has no other specific symptoms She was on holiday in China 7 months ago On examination she looks well and has a temperature of 387degC There is no lymphadenopathy and no rashes Examination is entirely normal
Results of investigations are as follows
haemoglobin 126 gdl (120ndash160)
total white blood cell count 132 times 109litre (43ndash108)
neutrophil count 115 times 109litre (25ndash75)
Platelet count 244 times 109litre (150ndash400)
Blood film neutrophilia with left shift
erythrocyte sedimentation rate 63 mmh (1ndash20)
c-reactive protein 219 mglitre (0ndash5)
Blood culture Streptococcus intermedius
from anaerobic bottle only
csf culture negative
Magnetic resonance imaging (MRI) of the brain shows acute frontal sinusitis with a large intracranial frontal extra-dural empyema (Figure 4)
1 Which of the following would be appropriate management Choose ONE answer ONLY from the followingA A 12-week course of intravenous antibioticsB Drainage of the frontal sinus followed by 2 weeks of
intravenous antibioticsC Drainage of the empyema followed by 2 weeks of
intravenous antibioticsD Drainage of the empyema and the frontal sinus
followed by 2 weeks of oral antibiotics
1151
1152
1153
1154
1155
1156
1157
1158
1159
1200
50ms 1mV
Figure 3 electromyogram recording from the patient Figure 4 Parasagittal section from mri scan of patient
Paediatrics and child health 184 204 copy 2008 elsevier ltd all rights reserved
self-assessment
E Drainage of the empyema and the frontal sinus followed by 8 weeks of intravenous antibiotics
2 Streptococcus intermedius is a potential pathogen in which of the following infections Choose ONE answer ONLY from the followingA Liver abscessB Urinary tract infectionC MeningitisD Thoracic empyemaE Pneumonia
3 Which of the following statements regarding lsquopyrexia of unknown originrsquo in children is false Choose ONE answer ONLY from the followingA Malignancy is the underlying pathology in 5ndash15 of
casesB An aetiology will be found in over 90 of casesC The most common cause is infectionD A rheumatological cause is found in 10ndash20 of casesE Familial Mediterranean fever can occur in children of
non-Mediterranean ethnicity
Answers
Case 11 AThe anion gap is a useful tool to differentiate the causes of a metabolic acidosis It is calculated by the equation
Anion gap = [Na K ] [Cl HCO ]3+ + minus minus+ minus +
It represents the effect of unmeasured anions on the plasma pH and is normally 10ndash18 mmollitre
2 CMicrovillus inclusion disease is a severe autosomal recessive enteropathy that is typically apparent within hours or days after birth It is the second most common cause of protracted diarrhoea in the newborn after infectious causes It is characterized by severe yellow watery diarrhoea and malabsorption due to hypoplasia andor atrophy of the villi of the small intestine secondary to an inherited defect in the brush border membrane This results in severe dehydration malnutrition and metabolic acidosis due to bicarbonate loss from the gut
3 CDiagnosis of microvillus inclusion disease is made on small bowel biopsy Electron microscopy findings are of intracellular brush border inclusions and densely packed apical cytoplasmic vesicular bodies indicating microvillous atrophy There is no cure Treatment is supportive with total parenteral nutrition and consideration of small bowel transplantation
Further reAding
Goulet O ruemmele f causes and management of intestinal failure
in children Gastroenterology 2006 130(suppl 1) s16ndash28
rhoads Jm Vogler rc lacey sr et al microvillus inclusion disease
In vitro jejunal electrolyte transport Gastroenterology 1991
100 811ndash817
Case 21 CGianottindashCrosti syndrome is a distinct self-limiting rash commonly associated with viral infections in children between 2 and 6 years of age It presents as multiple pink to redminusbrown papules or papulovesicles which may be pruritic and can become confluent Gianotti and Crosti initially described the exanthema as associated with hepatitis B virus and they termed it papular acrodermatitis of childhood It can occur in several viral diseases eg hepatitis A B and C coxsackie viruses and cytomegalovirus
2 BHepatitis is a syndrome characterized by inflammation or injury of liver cells which may develop into cell necrosis and subsequently fibrosis andor cirrhosis Biochemically there are raised liver enzymes The degree of transaminase elevation does not correlate with the severity of the disease process Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of viral hepatitis
3 DHepatitis B infection is transmitted via blood sexually or vertically Infection may be acute or chronic Diagnostic markers are the presence of surface antigen (HBsAg) and HBV DNA The presence of e antigen (HBeAg) indicates high infectivity Infected newborns have a 95 risk of becoming carriers this risk decreases with infection acquired later in childhood Approximately 15ndash25 of HBV carriers will die from cirrhosis or hepatocellular carcinoma Extrahepatic findings are more common in older children and include membranous glomerulonephritis and GianottiminusCrosti syndrome Fulminant hepatic failure occurs in severe cases resulting in persistent jaundice encephalopathy and coagulopathy Management includes counselling family members monitoring for ongoing liver disease and consideration of antiviral therapy
Further reAding
Brandt O abeck d Gianotti r Burgdorf W Gianotti crosti
syndrome J Am Acad Dermatol 2006 54 136ndash145
slowik mK Jhaveri r hepatitis B and c viruses in infants and
young children Semin Pediatr Infect Dis 2005 16 296ndash305
Case 31 CHypercalcaemia is uncommon in infancy The most common symptoms in this age group are irritability vomiting and constipation It may be a manifestation of Williams syndrome vitamin D or calcium excess as well as disorders associated with reduced bone formation such as hypophosphatasia or increased bone resorption such as malignancy Occasionally
Paediatrics and child health 184 205 copy 2008 elsevier ltd all rights reserved
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-
self-assessment
Case 1A term male infant born to consanguineous parents is assessed at 24 h of age due to poor feeding profuse yellow watery diar-rhoea and irritability He weighed 32 kg at birth and delivery was uneventful There was no polyhydramnios He has been breastfed since birth On examination he is pale with a non-tender but distended abdomen and reduced bowel sounds His weight is 275 kg and he looks dehydrated Examination is otherwise normal
Initial investigations (normal values in parentheses) showed
sodium 149 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 65 mmollitre (25ndash75)
creatinine 147 μmollitre (40ndash110)
chloride 119 mmollitre (95ndash105)
haemoglobin 172 gdl (140ndash200)
White blood cell count 80 times 109litre (100ndash260)
Platelet count 302 times 109litre (150ndash400)
arterial blood gas
ph 720 (730ndash745)
PcO2 23 kPa (46ndash60)
Bicarbonate 68 mmollitre (220ndash260)
Base excess minus186 mmollitre (minus20 to +20)
lactate 59 mmollitre (06ndash24)
An abdominal X-ray shows distended bowel loops with no intramural thickening or pneumoperitoneum (Figure 1)
He was given nil by mouth and received intravenous fluids and antibiotics His dehydration improved but the metabolic acidosis and diarrhoea persisted despite receiving no enteral feeds and the commencement of total parenteral nutrition Blood and stool cultures were negative
1 Which of the following best describes these results Choose ONE answer ONLY from the followingA Hypernatraemia hyperchloraemic metabolic acidosis
with increased anion gapB Hypernatraemia hyperchloraemic metabolic acidosis
with normal anion gap
Manish Sadarangani BM BCh MA MRCPCH is Clinical Research Fellow
at the Department of Paediatrics University of Oxford Centre for
Clinical Vaccinology and Tropical Medicine Churchill Hospital
Oxford OX3 7LJ UK
Shabna Rajapaksa MB BChir MA MRCPCH is Specialist Registrar in
Paediatrics at the Paediatric Intensive Care Unit John Radcliffe
Hospital Oxford OX3 9DU UK
Nicholas Mann MD FRCP FRCPCH DCH is Consultant Paediatrician at the
Department of Paediatrics Royal Berkshire Hospital Reading RG1
5AN UK
self-assessment
C Hypernatraemic dehydration and compensated metabolic acidosis
D Acute renal failureE Renal tubular acidosis
2 What is the likely diagnosis Choose ONE answer ONLY from the followingA Hirschsprung disease ndash long segmentB Cystic fibrosis with meconium ileusC Microvillus inclusion diseaseD Cowrsquos milk protein intoleranceE Lactose intolerance
3 What is the investigation of choice Choose ONE answer ONLY from the followingA Rectal biopsy with staining for acetylcholine receptorsB Immunoreactive trypsinC Gastrointestinal endoscopy and biopsyD Stool microscopy and cultureE Stool reducing substances
Case 2A 4-year-old boy presents with a 3 d history of jaundice and a florid rash He has had orange urine and there is no change in his stool colour His family originate from Kosovo and have lived in the UK for the last 8 years He has never left the UK There is no history of blood transfusion or sex-ual abuse The grandmother was recently diagnosed with hepatitis B
On examination he is well apyrexial and mildly jaundiced with cervical and axillary lymphadenopathy He has an exten-sive papular rash over the face extremities and trunk (Figure 2) There is 3 cm hepatomegaly with no splenomegaly or ascites Examination is otherwise normal
Figure 1 abdominal X-ray of baby
Paediatrics and child health 184 202 copy 2008 elsevier ltd all rights reserved
self-assessment
Initial investigations are as follows
haemoglobin 110 gdl (113ndash135)
White blood cell count 108 times 109litre (50ndash150)
Platelet count 278 times 109litre (150ndash400)
inr 10 (08ndash12)
aPt ratio 10 (08ndash13)
sodium 140 mmollitre (135ndash145)
Potassium 42 mmollitre (35ndash50)
Urea 56 mmollitre (25ndash75)
creatinine 65 μmollitre (45ndash120)
total bilirubin 66 μmollitre (0ndash15)
conjugated bilirubin 23 μmollitre (0ndash10)
alanine aminotransferase (alt) 2033 iUlitre (0ndash35)
alkaline phosphatase 987 iUlitre (71ndash234)
Gamma-glutamyl transferase (GGt) 870 iUlitre (0ndash51)
1 What is the name of this rash Choose ONE answer ONLY from the followingA Erythema multiformeB Erythema migransC GianottiminusCrosti syndromeD EczemaE Dermatitis herpetiformis
2 What is the most likely diagnosis Choose ONE Answer ONLY from the followingA Autoimmune hepatitisB Hepatitis BC Hepatitis DD Wilson diseaseE Alpha-1 antitrypsin deficiency
3 What is the best means of management Choose ONE answer ONLY from the followingA Isolation until the jaundice disappearsB ImmunosuppressionC Copper chelating agents and genetic counsellingD Patient and family education with consideration of
antiviral agentsE Liver transplantation
Case 3A 10-month-old boy presents with 3 weeks of vomiting and constipation ndash he is passing hard stools every 2ndash3 days He has fallen from the 9th to below the 04th centile in the last 6 weeks He passed meconium within the first 24 h of life On examina-tion he looks pale and there are some dysmorphic features ndash a short nose long philtrum and wide mouth He has normal heart sounds with a grade 3 ejection systolic murmur loudest at the upper right sternal edge Examination is otherwise normal
Initial investigations are as follows
haemoglobin 91 gdl (113ndash141)
total white blood cell count 124 times 109litre (60ndash170)
Platelet count 407 times 109litre (150ndash400)
sodium 144 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 78 mmollitre (25ndash75)
creatinine 78 μmollitre (45ndash120)
albumin 52 glitre (35ndash50)
corrected calcium 384 mmollitre (238ndash263)
Phosphate 167 mmollitre (099ndash157)
1 What is the most likely diagnosis Choose ONE answer ONLY from the followingA HyperparathyroidismB Acute leukaemiaC Williams syndromeD Hypervitaminosis DE Familial hypocalciuric hypercalcaemia
2 Which investigation would be most useful in establishing the diagnosis Choose ONE answer ONLY from the followingA Intact parathyroid hormone assayB Blood filmC Fluorescent in-situ hybridization for 7q1123 deletionD 25-hydroxyvitamin D assayE Urine calciumcreatinine ratio
3 Which of the following treatments would not be suitable for this patient Choose ONE answer ONLY from the followingA Low calcium dietB Normal saline infusionC FurosemideD CorticosteroidsE Bisphosphonates
Case 4A 10-week-old girl presents with a 2-day history of poor feed-ing Her mother has been concerned about weakness since birth She only has a flicker of movement in the arms none in the legs and has a weak cry She has been passing urine and opening her bowels normally She was born at full term by normal delivery and did not require any resuscitation at birth Normal fetal movements were felt antenatally and there was no polyhydramnios She is the first child of non- consanguineous parents and there is no significant family his-tory On examination she is alert and fixing and following appropriately She has a weak cry and a weak suck There is reduced central and peripheral tone with marked head lag
Figure 2 rash found on examination
Paediatrics and child health 184 203 copy 2008 elsevier ltd all rights reserved
self-assessment
Muscle power is grade 3 out of 5 in the arms and legs There is no muscle or tongue fasciculation and she has absent reflexes throughout The remainder of the examination is normal
Electromyogram shows irregular polyphasic motor unit potentials with marked instability consistent with a dener-vating and re-innervating process (Figure 3)
1 Which of the following additional investigations may be helpful Choose ONE answer ONLY from the followingA Nerve conduction studiesB Creatine kinase assayC Muscle biopsyD SMN1 gene analysisE All of the above
2 What is the most likely cause of this childrsquos symptoms Choose ONE answer ONLY from the followingA Congenital myotonic dystrophyB Duchenne muscular dystrophyC PraderminusWilli syndromeD Spinal muscular atrophyE Mitochondrial myopathy
3 What is the mode of inheritance of this disease Choose ONE answer ONLY from the followingA X-linked recessiveB Autosomal recessiveC Autosomal dominantD MitochondrialE Sporadic
Case 5A 13-year-old girl presents with a 3-week history of fever up to 40degC night sweats and headache She has a reduced appetite with some weight loss She has no other specific symptoms She was on holiday in China 7 months ago On examination she looks well and has a temperature of 387degC There is no lymphadenopathy and no rashes Examination is entirely normal
Results of investigations are as follows
haemoglobin 126 gdl (120ndash160)
total white blood cell count 132 times 109litre (43ndash108)
neutrophil count 115 times 109litre (25ndash75)
Platelet count 244 times 109litre (150ndash400)
Blood film neutrophilia with left shift
erythrocyte sedimentation rate 63 mmh (1ndash20)
c-reactive protein 219 mglitre (0ndash5)
Blood culture Streptococcus intermedius
from anaerobic bottle only
csf culture negative
Magnetic resonance imaging (MRI) of the brain shows acute frontal sinusitis with a large intracranial frontal extra-dural empyema (Figure 4)
1 Which of the following would be appropriate management Choose ONE answer ONLY from the followingA A 12-week course of intravenous antibioticsB Drainage of the frontal sinus followed by 2 weeks of
intravenous antibioticsC Drainage of the empyema followed by 2 weeks of
intravenous antibioticsD Drainage of the empyema and the frontal sinus
followed by 2 weeks of oral antibiotics
1151
1152
1153
1154
1155
1156
1157
1158
1159
1200
50ms 1mV
Figure 3 electromyogram recording from the patient Figure 4 Parasagittal section from mri scan of patient
Paediatrics and child health 184 204 copy 2008 elsevier ltd all rights reserved
self-assessment
E Drainage of the empyema and the frontal sinus followed by 8 weeks of intravenous antibiotics
2 Streptococcus intermedius is a potential pathogen in which of the following infections Choose ONE answer ONLY from the followingA Liver abscessB Urinary tract infectionC MeningitisD Thoracic empyemaE Pneumonia
3 Which of the following statements regarding lsquopyrexia of unknown originrsquo in children is false Choose ONE answer ONLY from the followingA Malignancy is the underlying pathology in 5ndash15 of
casesB An aetiology will be found in over 90 of casesC The most common cause is infectionD A rheumatological cause is found in 10ndash20 of casesE Familial Mediterranean fever can occur in children of
non-Mediterranean ethnicity
Answers
Case 11 AThe anion gap is a useful tool to differentiate the causes of a metabolic acidosis It is calculated by the equation
Anion gap = [Na K ] [Cl HCO ]3+ + minus minus+ minus +
It represents the effect of unmeasured anions on the plasma pH and is normally 10ndash18 mmollitre
2 CMicrovillus inclusion disease is a severe autosomal recessive enteropathy that is typically apparent within hours or days after birth It is the second most common cause of protracted diarrhoea in the newborn after infectious causes It is characterized by severe yellow watery diarrhoea and malabsorption due to hypoplasia andor atrophy of the villi of the small intestine secondary to an inherited defect in the brush border membrane This results in severe dehydration malnutrition and metabolic acidosis due to bicarbonate loss from the gut
3 CDiagnosis of microvillus inclusion disease is made on small bowel biopsy Electron microscopy findings are of intracellular brush border inclusions and densely packed apical cytoplasmic vesicular bodies indicating microvillous atrophy There is no cure Treatment is supportive with total parenteral nutrition and consideration of small bowel transplantation
Further reAding
Goulet O ruemmele f causes and management of intestinal failure
in children Gastroenterology 2006 130(suppl 1) s16ndash28
rhoads Jm Vogler rc lacey sr et al microvillus inclusion disease
In vitro jejunal electrolyte transport Gastroenterology 1991
100 811ndash817
Case 21 CGianottindashCrosti syndrome is a distinct self-limiting rash commonly associated with viral infections in children between 2 and 6 years of age It presents as multiple pink to redminusbrown papules or papulovesicles which may be pruritic and can become confluent Gianotti and Crosti initially described the exanthema as associated with hepatitis B virus and they termed it papular acrodermatitis of childhood It can occur in several viral diseases eg hepatitis A B and C coxsackie viruses and cytomegalovirus
2 BHepatitis is a syndrome characterized by inflammation or injury of liver cells which may develop into cell necrosis and subsequently fibrosis andor cirrhosis Biochemically there are raised liver enzymes The degree of transaminase elevation does not correlate with the severity of the disease process Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of viral hepatitis
3 DHepatitis B infection is transmitted via blood sexually or vertically Infection may be acute or chronic Diagnostic markers are the presence of surface antigen (HBsAg) and HBV DNA The presence of e antigen (HBeAg) indicates high infectivity Infected newborns have a 95 risk of becoming carriers this risk decreases with infection acquired later in childhood Approximately 15ndash25 of HBV carriers will die from cirrhosis or hepatocellular carcinoma Extrahepatic findings are more common in older children and include membranous glomerulonephritis and GianottiminusCrosti syndrome Fulminant hepatic failure occurs in severe cases resulting in persistent jaundice encephalopathy and coagulopathy Management includes counselling family members monitoring for ongoing liver disease and consideration of antiviral therapy
Further reAding
Brandt O abeck d Gianotti r Burgdorf W Gianotti crosti
syndrome J Am Acad Dermatol 2006 54 136ndash145
slowik mK Jhaveri r hepatitis B and c viruses in infants and
young children Semin Pediatr Infect Dis 2005 16 296ndash305
Case 31 CHypercalcaemia is uncommon in infancy The most common symptoms in this age group are irritability vomiting and constipation It may be a manifestation of Williams syndrome vitamin D or calcium excess as well as disorders associated with reduced bone formation such as hypophosphatasia or increased bone resorption such as malignancy Occasionally
Paediatrics and child health 184 205 copy 2008 elsevier ltd all rights reserved
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-
self-assessment
Initial investigations are as follows
haemoglobin 110 gdl (113ndash135)
White blood cell count 108 times 109litre (50ndash150)
Platelet count 278 times 109litre (150ndash400)
inr 10 (08ndash12)
aPt ratio 10 (08ndash13)
sodium 140 mmollitre (135ndash145)
Potassium 42 mmollitre (35ndash50)
Urea 56 mmollitre (25ndash75)
creatinine 65 μmollitre (45ndash120)
total bilirubin 66 μmollitre (0ndash15)
conjugated bilirubin 23 μmollitre (0ndash10)
alanine aminotransferase (alt) 2033 iUlitre (0ndash35)
alkaline phosphatase 987 iUlitre (71ndash234)
Gamma-glutamyl transferase (GGt) 870 iUlitre (0ndash51)
1 What is the name of this rash Choose ONE answer ONLY from the followingA Erythema multiformeB Erythema migransC GianottiminusCrosti syndromeD EczemaE Dermatitis herpetiformis
2 What is the most likely diagnosis Choose ONE Answer ONLY from the followingA Autoimmune hepatitisB Hepatitis BC Hepatitis DD Wilson diseaseE Alpha-1 antitrypsin deficiency
3 What is the best means of management Choose ONE answer ONLY from the followingA Isolation until the jaundice disappearsB ImmunosuppressionC Copper chelating agents and genetic counsellingD Patient and family education with consideration of
antiviral agentsE Liver transplantation
Case 3A 10-month-old boy presents with 3 weeks of vomiting and constipation ndash he is passing hard stools every 2ndash3 days He has fallen from the 9th to below the 04th centile in the last 6 weeks He passed meconium within the first 24 h of life On examina-tion he looks pale and there are some dysmorphic features ndash a short nose long philtrum and wide mouth He has normal heart sounds with a grade 3 ejection systolic murmur loudest at the upper right sternal edge Examination is otherwise normal
Initial investigations are as follows
haemoglobin 91 gdl (113ndash141)
total white blood cell count 124 times 109litre (60ndash170)
Platelet count 407 times 109litre (150ndash400)
sodium 144 mmollitre (135ndash145)
Potassium 37 mmollitre (35ndash50)
Urea 78 mmollitre (25ndash75)
creatinine 78 μmollitre (45ndash120)
albumin 52 glitre (35ndash50)
corrected calcium 384 mmollitre (238ndash263)
Phosphate 167 mmollitre (099ndash157)
1 What is the most likely diagnosis Choose ONE answer ONLY from the followingA HyperparathyroidismB Acute leukaemiaC Williams syndromeD Hypervitaminosis DE Familial hypocalciuric hypercalcaemia
2 Which investigation would be most useful in establishing the diagnosis Choose ONE answer ONLY from the followingA Intact parathyroid hormone assayB Blood filmC Fluorescent in-situ hybridization for 7q1123 deletionD 25-hydroxyvitamin D assayE Urine calciumcreatinine ratio
3 Which of the following treatments would not be suitable for this patient Choose ONE answer ONLY from the followingA Low calcium dietB Normal saline infusionC FurosemideD CorticosteroidsE Bisphosphonates
Case 4A 10-week-old girl presents with a 2-day history of poor feed-ing Her mother has been concerned about weakness since birth She only has a flicker of movement in the arms none in the legs and has a weak cry She has been passing urine and opening her bowels normally She was born at full term by normal delivery and did not require any resuscitation at birth Normal fetal movements were felt antenatally and there was no polyhydramnios She is the first child of non- consanguineous parents and there is no significant family his-tory On examination she is alert and fixing and following appropriately She has a weak cry and a weak suck There is reduced central and peripheral tone with marked head lag
Figure 2 rash found on examination
Paediatrics and child health 184 203 copy 2008 elsevier ltd all rights reserved
self-assessment
Muscle power is grade 3 out of 5 in the arms and legs There is no muscle or tongue fasciculation and she has absent reflexes throughout The remainder of the examination is normal
Electromyogram shows irregular polyphasic motor unit potentials with marked instability consistent with a dener-vating and re-innervating process (Figure 3)
1 Which of the following additional investigations may be helpful Choose ONE answer ONLY from the followingA Nerve conduction studiesB Creatine kinase assayC Muscle biopsyD SMN1 gene analysisE All of the above
2 What is the most likely cause of this childrsquos symptoms Choose ONE answer ONLY from the followingA Congenital myotonic dystrophyB Duchenne muscular dystrophyC PraderminusWilli syndromeD Spinal muscular atrophyE Mitochondrial myopathy
3 What is the mode of inheritance of this disease Choose ONE answer ONLY from the followingA X-linked recessiveB Autosomal recessiveC Autosomal dominantD MitochondrialE Sporadic
Case 5A 13-year-old girl presents with a 3-week history of fever up to 40degC night sweats and headache She has a reduced appetite with some weight loss She has no other specific symptoms She was on holiday in China 7 months ago On examination she looks well and has a temperature of 387degC There is no lymphadenopathy and no rashes Examination is entirely normal
Results of investigations are as follows
haemoglobin 126 gdl (120ndash160)
total white blood cell count 132 times 109litre (43ndash108)
neutrophil count 115 times 109litre (25ndash75)
Platelet count 244 times 109litre (150ndash400)
Blood film neutrophilia with left shift
erythrocyte sedimentation rate 63 mmh (1ndash20)
c-reactive protein 219 mglitre (0ndash5)
Blood culture Streptococcus intermedius
from anaerobic bottle only
csf culture negative
Magnetic resonance imaging (MRI) of the brain shows acute frontal sinusitis with a large intracranial frontal extra-dural empyema (Figure 4)
1 Which of the following would be appropriate management Choose ONE answer ONLY from the followingA A 12-week course of intravenous antibioticsB Drainage of the frontal sinus followed by 2 weeks of
intravenous antibioticsC Drainage of the empyema followed by 2 weeks of
intravenous antibioticsD Drainage of the empyema and the frontal sinus
followed by 2 weeks of oral antibiotics
1151
1152
1153
1154
1155
1156
1157
1158
1159
1200
50ms 1mV
Figure 3 electromyogram recording from the patient Figure 4 Parasagittal section from mri scan of patient
Paediatrics and child health 184 204 copy 2008 elsevier ltd all rights reserved
self-assessment
E Drainage of the empyema and the frontal sinus followed by 8 weeks of intravenous antibiotics
2 Streptococcus intermedius is a potential pathogen in which of the following infections Choose ONE answer ONLY from the followingA Liver abscessB Urinary tract infectionC MeningitisD Thoracic empyemaE Pneumonia
3 Which of the following statements regarding lsquopyrexia of unknown originrsquo in children is false Choose ONE answer ONLY from the followingA Malignancy is the underlying pathology in 5ndash15 of
casesB An aetiology will be found in over 90 of casesC The most common cause is infectionD A rheumatological cause is found in 10ndash20 of casesE Familial Mediterranean fever can occur in children of
non-Mediterranean ethnicity
Answers
Case 11 AThe anion gap is a useful tool to differentiate the causes of a metabolic acidosis It is calculated by the equation
Anion gap = [Na K ] [Cl HCO ]3+ + minus minus+ minus +
It represents the effect of unmeasured anions on the plasma pH and is normally 10ndash18 mmollitre
2 CMicrovillus inclusion disease is a severe autosomal recessive enteropathy that is typically apparent within hours or days after birth It is the second most common cause of protracted diarrhoea in the newborn after infectious causes It is characterized by severe yellow watery diarrhoea and malabsorption due to hypoplasia andor atrophy of the villi of the small intestine secondary to an inherited defect in the brush border membrane This results in severe dehydration malnutrition and metabolic acidosis due to bicarbonate loss from the gut
3 CDiagnosis of microvillus inclusion disease is made on small bowel biopsy Electron microscopy findings are of intracellular brush border inclusions and densely packed apical cytoplasmic vesicular bodies indicating microvillous atrophy There is no cure Treatment is supportive with total parenteral nutrition and consideration of small bowel transplantation
Further reAding
Goulet O ruemmele f causes and management of intestinal failure
in children Gastroenterology 2006 130(suppl 1) s16ndash28
rhoads Jm Vogler rc lacey sr et al microvillus inclusion disease
In vitro jejunal electrolyte transport Gastroenterology 1991
100 811ndash817
Case 21 CGianottindashCrosti syndrome is a distinct self-limiting rash commonly associated with viral infections in children between 2 and 6 years of age It presents as multiple pink to redminusbrown papules or papulovesicles which may be pruritic and can become confluent Gianotti and Crosti initially described the exanthema as associated with hepatitis B virus and they termed it papular acrodermatitis of childhood It can occur in several viral diseases eg hepatitis A B and C coxsackie viruses and cytomegalovirus
2 BHepatitis is a syndrome characterized by inflammation or injury of liver cells which may develop into cell necrosis and subsequently fibrosis andor cirrhosis Biochemically there are raised liver enzymes The degree of transaminase elevation does not correlate with the severity of the disease process Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of viral hepatitis
3 DHepatitis B infection is transmitted via blood sexually or vertically Infection may be acute or chronic Diagnostic markers are the presence of surface antigen (HBsAg) and HBV DNA The presence of e antigen (HBeAg) indicates high infectivity Infected newborns have a 95 risk of becoming carriers this risk decreases with infection acquired later in childhood Approximately 15ndash25 of HBV carriers will die from cirrhosis or hepatocellular carcinoma Extrahepatic findings are more common in older children and include membranous glomerulonephritis and GianottiminusCrosti syndrome Fulminant hepatic failure occurs in severe cases resulting in persistent jaundice encephalopathy and coagulopathy Management includes counselling family members monitoring for ongoing liver disease and consideration of antiviral therapy
Further reAding
Brandt O abeck d Gianotti r Burgdorf W Gianotti crosti
syndrome J Am Acad Dermatol 2006 54 136ndash145
slowik mK Jhaveri r hepatitis B and c viruses in infants and
young children Semin Pediatr Infect Dis 2005 16 296ndash305
Case 31 CHypercalcaemia is uncommon in infancy The most common symptoms in this age group are irritability vomiting and constipation It may be a manifestation of Williams syndrome vitamin D or calcium excess as well as disorders associated with reduced bone formation such as hypophosphatasia or increased bone resorption such as malignancy Occasionally
Paediatrics and child health 184 205 copy 2008 elsevier ltd all rights reserved
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-
self-assessment
Muscle power is grade 3 out of 5 in the arms and legs There is no muscle or tongue fasciculation and she has absent reflexes throughout The remainder of the examination is normal
Electromyogram shows irregular polyphasic motor unit potentials with marked instability consistent with a dener-vating and re-innervating process (Figure 3)
1 Which of the following additional investigations may be helpful Choose ONE answer ONLY from the followingA Nerve conduction studiesB Creatine kinase assayC Muscle biopsyD SMN1 gene analysisE All of the above
2 What is the most likely cause of this childrsquos symptoms Choose ONE answer ONLY from the followingA Congenital myotonic dystrophyB Duchenne muscular dystrophyC PraderminusWilli syndromeD Spinal muscular atrophyE Mitochondrial myopathy
3 What is the mode of inheritance of this disease Choose ONE answer ONLY from the followingA X-linked recessiveB Autosomal recessiveC Autosomal dominantD MitochondrialE Sporadic
Case 5A 13-year-old girl presents with a 3-week history of fever up to 40degC night sweats and headache She has a reduced appetite with some weight loss She has no other specific symptoms She was on holiday in China 7 months ago On examination she looks well and has a temperature of 387degC There is no lymphadenopathy and no rashes Examination is entirely normal
Results of investigations are as follows
haemoglobin 126 gdl (120ndash160)
total white blood cell count 132 times 109litre (43ndash108)
neutrophil count 115 times 109litre (25ndash75)
Platelet count 244 times 109litre (150ndash400)
Blood film neutrophilia with left shift
erythrocyte sedimentation rate 63 mmh (1ndash20)
c-reactive protein 219 mglitre (0ndash5)
Blood culture Streptococcus intermedius
from anaerobic bottle only
csf culture negative
Magnetic resonance imaging (MRI) of the brain shows acute frontal sinusitis with a large intracranial frontal extra-dural empyema (Figure 4)
1 Which of the following would be appropriate management Choose ONE answer ONLY from the followingA A 12-week course of intravenous antibioticsB Drainage of the frontal sinus followed by 2 weeks of
intravenous antibioticsC Drainage of the empyema followed by 2 weeks of
intravenous antibioticsD Drainage of the empyema and the frontal sinus
followed by 2 weeks of oral antibiotics
1151
1152
1153
1154
1155
1156
1157
1158
1159
1200
50ms 1mV
Figure 3 electromyogram recording from the patient Figure 4 Parasagittal section from mri scan of patient
Paediatrics and child health 184 204 copy 2008 elsevier ltd all rights reserved
self-assessment
E Drainage of the empyema and the frontal sinus followed by 8 weeks of intravenous antibiotics
2 Streptococcus intermedius is a potential pathogen in which of the following infections Choose ONE answer ONLY from the followingA Liver abscessB Urinary tract infectionC MeningitisD Thoracic empyemaE Pneumonia
3 Which of the following statements regarding lsquopyrexia of unknown originrsquo in children is false Choose ONE answer ONLY from the followingA Malignancy is the underlying pathology in 5ndash15 of
casesB An aetiology will be found in over 90 of casesC The most common cause is infectionD A rheumatological cause is found in 10ndash20 of casesE Familial Mediterranean fever can occur in children of
non-Mediterranean ethnicity
Answers
Case 11 AThe anion gap is a useful tool to differentiate the causes of a metabolic acidosis It is calculated by the equation
Anion gap = [Na K ] [Cl HCO ]3+ + minus minus+ minus +
It represents the effect of unmeasured anions on the plasma pH and is normally 10ndash18 mmollitre
2 CMicrovillus inclusion disease is a severe autosomal recessive enteropathy that is typically apparent within hours or days after birth It is the second most common cause of protracted diarrhoea in the newborn after infectious causes It is characterized by severe yellow watery diarrhoea and malabsorption due to hypoplasia andor atrophy of the villi of the small intestine secondary to an inherited defect in the brush border membrane This results in severe dehydration malnutrition and metabolic acidosis due to bicarbonate loss from the gut
3 CDiagnosis of microvillus inclusion disease is made on small bowel biopsy Electron microscopy findings are of intracellular brush border inclusions and densely packed apical cytoplasmic vesicular bodies indicating microvillous atrophy There is no cure Treatment is supportive with total parenteral nutrition and consideration of small bowel transplantation
Further reAding
Goulet O ruemmele f causes and management of intestinal failure
in children Gastroenterology 2006 130(suppl 1) s16ndash28
rhoads Jm Vogler rc lacey sr et al microvillus inclusion disease
In vitro jejunal electrolyte transport Gastroenterology 1991
100 811ndash817
Case 21 CGianottindashCrosti syndrome is a distinct self-limiting rash commonly associated with viral infections in children between 2 and 6 years of age It presents as multiple pink to redminusbrown papules or papulovesicles which may be pruritic and can become confluent Gianotti and Crosti initially described the exanthema as associated with hepatitis B virus and they termed it papular acrodermatitis of childhood It can occur in several viral diseases eg hepatitis A B and C coxsackie viruses and cytomegalovirus
2 BHepatitis is a syndrome characterized by inflammation or injury of liver cells which may develop into cell necrosis and subsequently fibrosis andor cirrhosis Biochemically there are raised liver enzymes The degree of transaminase elevation does not correlate with the severity of the disease process Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of viral hepatitis
3 DHepatitis B infection is transmitted via blood sexually or vertically Infection may be acute or chronic Diagnostic markers are the presence of surface antigen (HBsAg) and HBV DNA The presence of e antigen (HBeAg) indicates high infectivity Infected newborns have a 95 risk of becoming carriers this risk decreases with infection acquired later in childhood Approximately 15ndash25 of HBV carriers will die from cirrhosis or hepatocellular carcinoma Extrahepatic findings are more common in older children and include membranous glomerulonephritis and GianottiminusCrosti syndrome Fulminant hepatic failure occurs in severe cases resulting in persistent jaundice encephalopathy and coagulopathy Management includes counselling family members monitoring for ongoing liver disease and consideration of antiviral therapy
Further reAding
Brandt O abeck d Gianotti r Burgdorf W Gianotti crosti
syndrome J Am Acad Dermatol 2006 54 136ndash145
slowik mK Jhaveri r hepatitis B and c viruses in infants and
young children Semin Pediatr Infect Dis 2005 16 296ndash305
Case 31 CHypercalcaemia is uncommon in infancy The most common symptoms in this age group are irritability vomiting and constipation It may be a manifestation of Williams syndrome vitamin D or calcium excess as well as disorders associated with reduced bone formation such as hypophosphatasia or increased bone resorption such as malignancy Occasionally
Paediatrics and child health 184 205 copy 2008 elsevier ltd all rights reserved
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-
self-assessment
E Drainage of the empyema and the frontal sinus followed by 8 weeks of intravenous antibiotics
2 Streptococcus intermedius is a potential pathogen in which of the following infections Choose ONE answer ONLY from the followingA Liver abscessB Urinary tract infectionC MeningitisD Thoracic empyemaE Pneumonia
3 Which of the following statements regarding lsquopyrexia of unknown originrsquo in children is false Choose ONE answer ONLY from the followingA Malignancy is the underlying pathology in 5ndash15 of
casesB An aetiology will be found in over 90 of casesC The most common cause is infectionD A rheumatological cause is found in 10ndash20 of casesE Familial Mediterranean fever can occur in children of
non-Mediterranean ethnicity
Answers
Case 11 AThe anion gap is a useful tool to differentiate the causes of a metabolic acidosis It is calculated by the equation
Anion gap = [Na K ] [Cl HCO ]3+ + minus minus+ minus +
It represents the effect of unmeasured anions on the plasma pH and is normally 10ndash18 mmollitre
2 CMicrovillus inclusion disease is a severe autosomal recessive enteropathy that is typically apparent within hours or days after birth It is the second most common cause of protracted diarrhoea in the newborn after infectious causes It is characterized by severe yellow watery diarrhoea and malabsorption due to hypoplasia andor atrophy of the villi of the small intestine secondary to an inherited defect in the brush border membrane This results in severe dehydration malnutrition and metabolic acidosis due to bicarbonate loss from the gut
3 CDiagnosis of microvillus inclusion disease is made on small bowel biopsy Electron microscopy findings are of intracellular brush border inclusions and densely packed apical cytoplasmic vesicular bodies indicating microvillous atrophy There is no cure Treatment is supportive with total parenteral nutrition and consideration of small bowel transplantation
Further reAding
Goulet O ruemmele f causes and management of intestinal failure
in children Gastroenterology 2006 130(suppl 1) s16ndash28
rhoads Jm Vogler rc lacey sr et al microvillus inclusion disease
In vitro jejunal electrolyte transport Gastroenterology 1991
100 811ndash817
Case 21 CGianottindashCrosti syndrome is a distinct self-limiting rash commonly associated with viral infections in children between 2 and 6 years of age It presents as multiple pink to redminusbrown papules or papulovesicles which may be pruritic and can become confluent Gianotti and Crosti initially described the exanthema as associated with hepatitis B virus and they termed it papular acrodermatitis of childhood It can occur in several viral diseases eg hepatitis A B and C coxsackie viruses and cytomegalovirus
2 BHepatitis is a syndrome characterized by inflammation or injury of liver cells which may develop into cell necrosis and subsequently fibrosis andor cirrhosis Biochemically there are raised liver enzymes The degree of transaminase elevation does not correlate with the severity of the disease process Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of viral hepatitis
3 DHepatitis B infection is transmitted via blood sexually or vertically Infection may be acute or chronic Diagnostic markers are the presence of surface antigen (HBsAg) and HBV DNA The presence of e antigen (HBeAg) indicates high infectivity Infected newborns have a 95 risk of becoming carriers this risk decreases with infection acquired later in childhood Approximately 15ndash25 of HBV carriers will die from cirrhosis or hepatocellular carcinoma Extrahepatic findings are more common in older children and include membranous glomerulonephritis and GianottiminusCrosti syndrome Fulminant hepatic failure occurs in severe cases resulting in persistent jaundice encephalopathy and coagulopathy Management includes counselling family members monitoring for ongoing liver disease and consideration of antiviral therapy
Further reAding
Brandt O abeck d Gianotti r Burgdorf W Gianotti crosti
syndrome J Am Acad Dermatol 2006 54 136ndash145
slowik mK Jhaveri r hepatitis B and c viruses in infants and
young children Semin Pediatr Infect Dis 2005 16 296ndash305
Case 31 CHypercalcaemia is uncommon in infancy The most common symptoms in this age group are irritability vomiting and constipation It may be a manifestation of Williams syndrome vitamin D or calcium excess as well as disorders associated with reduced bone formation such as hypophosphatasia or increased bone resorption such as malignancy Occasionally
Paediatrics and child health 184 205 copy 2008 elsevier ltd all rights reserved
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-
self-assessment
it may reflect an abnormality of the calcium sensing receptor ndash familial hypocalciuric hypercalcaemia ndash with an associated altered lsquoset pointrsquo Primary hyperparathyroidism is extremely rare in infancy
2 CWilliams syndrome is caused by a microdeletion of chromosome 7 at q1123 detected by fluorescent in-situ hybridization (FISH) testing The deleted portion of the chromosome includes the ELN gene that encodes the structural protein elastin The syndrome is characterized by dysmorphic facies (which may be difficult to detect in younger children) lsquostellate irisrsquo congenital heart disease (most commonly supravalvar aortic stenosis) global developmental delay and idiopathic hypercalcaemia Affected children are often overfriendly with an empathetic nature Medical management includes cardiology and ophthalmology assessments and renal tract ultrasound (for nephrocalcinosis) Infantile hypercalcaemia occurs in approximately 15 of children and is typically not severe
3 DTreatment of Williams syndrome may include rehydration with normal saline forced diuresis with saline infusion and furosemide a low calcium diet (including low calcium milk) or rarely bisphosphonates Corticosteroids are not used in Williams syndrome but may be helpful in malignancy-associated hypercalcaemia or vitamin D ingestion
Further reAding
american academy of Pediatrics health care supervision for
children with Williams syndrome Pediatrics 2001 107
1192ndash1204
shaw nJ Bishop nJ Bisphosphonate treatment of bone disease
Arch Dis Child 2005 90 494ndash499
Case 41 EThe term lsquofloppy infantrsquo is used to denote an infant with poor muscle tone affecting the limbs trunk and craniofacial musculature There are numerous aetiologies and establishing a specific diagnosis in the individual case can be labour intensive The concept of central versus peripheral disorders causing hypotonia is clinically useful The relative preservation of muscle power and hyperreflexia favours a central origin to the hypotonia while the combination of weakness and hypoareflexia favours a neuromuscular disorder Such a clear distinction however may not always be possible and the features may overlap in conditions where the pathology affects both the central nervous system and peripheral nerve
2 DThe spinal muscular atrophies (SMAs) comprise a group of autosomal recessive disorders involving degeneration of the anterior horn cells SMA type I (WerdnigminusHoffman disease) is the most common variety and presents in the first few months
of life with reduced spontaneous movements and a floppy posture Tongue fasciculation hyporeflexia and decreased fetal movements in utero complete the clinical picture Weakness usually involves the bulbar and respiratory muscles and infants develop pneumonia and respiratory failure Electromyogram (EMG) shows spontaneous fibrillation potentials and polyphasic motor unit potentials This EMG pattern suggests denervation and re-innervation which is consistent with a neurogenic rather than a muscular disorder Muscle biopsy has been largely replaced by genetic tests ndash 96 of cases have total or partial absence of the survival motor neuron gene (SMN1)
3 B
Further reAding
Prasad an Prasad c the floppy infant contribution of genetic and
metabolic disorders Brain Dev 2003 25 457ndash476
Case 51 EEmpyema (subdural or extradural) is the most common intracranial complication of sinusitis Presentation of a frontal extradural empyema can be with a boggy frontal bone swelling due to osteomyelitis called a lsquoPottrsquos puffy tumourrsquo which was first described in 1760 Further complications of empyema include raised intracranial pressure and cerebral vein thrombosis ndash if neuroimaging shows either of these lumbar puncture is contraindicated Management involves aggressive neurosurgical and ENT intervention and prolonged high-dose intravenous antibiotics
2 AMicroaerophilic and anaerobic bacteria are commonly identified from intracranial abscesses Streptococcus intermedius is a member of the Streptococcus milleri group which is responsible for abscess formation in the mouth lung liver brain appendix and soft tissues S intermedius is particularly associated with abscesses in the brain and liver These organisms constitute part of the normal flora of the human oral cavity but it is important to recognize their significance when they are isolated from blood cultures and to investigate appropriately
3 BThe standard definition of pyrexia of unknown origin is lsquofever persisting for more than 3 weeks and uncertain diagnosis after 1 week of investigationrsquo The commonest causes in children are infection (30ndash50) rheumatological (10ndash20) and malignancy (5ndash15) No diagnosis is made in up to 30 of cases
Further reAding
majeed ha differential diagnosis of fever of unknown origin in
children Curr Opin Rheumatol 2000 12 439ndash444
Paediatrics and child health 184 206 copy 2008 elsevier ltd all rights reserved
- sdarticle01
- sdarticle02
-
- Temperature control in the neonate
-
- Introduction
- Temperature control at delivery
- Transport
- Thermal care within the neonatal unit
- Transepidermal water loss
-
- Incubators
- Radiant heaters
- Maintenance of skin integrity
- Skin coverings
- Ventilator humidity
- Phototherapy
- Transepidermal water loss and skin maturation
-
- Temperature monitoring and its interpretation
- Conclusion
- References
-
- sdarticle03
-
- Investigation and management of impaired metabolic adaptation presenting as neonatal hypoglycaemia
-
- Introduction
- Fetal metabolism metabolic changes at birth and lsquotransitional hypoglycaemiarsquo
- Impaired metabolic adaptation
- Diagnosis of clinically significant hypoglycaemia
- Blood glucose monitoring
- Prevention and management of clinically significant hypoglycaemia
- Summary
- References
-
- sdarticle04
-
- Resuscitation of the term and premature baby
-
- Background
- Resuscitation at birth
-
- Preparation
- Cord clamping
- Assessment and temperature control
-
- Airway
-
- Endotracheal intubation
- Laryngeal masks
- Meconium
-
- Breathing
-
- Ventilation
-
- Circulation
- Drugs
-
- Adrenaline (epinephrine)
- Bicarbonate
- Volume
- Naloxone
-
- Non-response to resuscitation
- Outcome
- References
-
- sdarticle05
-
- Acidndashbase physiology and blood gas interpretation in the neonate
-
- Introduction
- What is understood by acid-base balance
- Maintaining acidndashbase balance
-
- Buffer systems
- Respiratory regulation
- Renal regulation
-
- Quantifying acidosis
- Strong ion theory
- Tissue oxygenation
- Clinical acidndashbase imbalances
-
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
-
- Interpreting blood gases
- References
-
- sdarticle06
-
- Recognition and management of neonatal seizures
-
- Aetiology
- Controversies in the clinical management of neonatal seizures
-
- Do neonatal convulsions cause brain injury
- Can we rely on clinical versus EEG diagnosis of neonatal shyconvulsions
- Do anticonvulsants stop neonatal seizures
- Do antiepileptic drugs cause brain damage
-
- Practical management of neonatal seizures
- References
-
- sdarticle08
-
- Emotional support for families of sick neonates
-
- Psychological impact of neonatal care for parents
- Interventions aimed at supporting parents
- Parent support programmes
- Conclusion
- References
-
- sdarticle09
-
- When should enteral feeds be started in preterm infants
-
- Key points in the history
- What else might be found on examination
- Balance of risks between starting and withholding feeds
- When starting feeds what volume should be used
- What else affects decisions and outcome
- References
-
- sdarticle10
-